Beetroot (Beta vulgaris) - Fortified Yogurt as a Natural Source of Levodopa Enhances in Rotenone – induced Parkinson's Disease in Mice

Beetroot (Beta vulgaris) - Fortified Yogurt as a Natural Source of Levodopa Enhances in Rotenone – induced Parkinson's Disease in Mice | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Beetroot ( Beta vulgaris ) - Fortified Yogurt as a Natural Source of Levodopa Enhances in Rotenone – induced Parkinson's Disease in Mice Radwa A. Shaheen, Mohamed M. Amin, Ereny W. Nagib, Rehab R. Hegazy, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7602198/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Parkinson’s disease (PD) is a common neurodegenerative disorder; however there is still a lacks of effective and safe treatments for it. Beetroot is a unique plant containing rich in betalains. It has shown protecting dopamine cells effects. Aim: To evaluate the effect of beetroot fortified yogurt on PD symptoms in mice compare to levodopa drug. Methods: PD was induced in adult male Swiss albino mice by rotenone through 9 subcutaneous injections 1.5 mg/kg; 3 times / week. Locomotor activity was assessed by behavioral tests, and some biochemical analyses were conducted. Results: Beetroot fortified yogurt improved locomotor activity and reduced PD markers such as, oxidative stress biomarkers, Neurotransmitters, Apoptotic Indices, Inflammatory Indices, liver and kidney functions and Constipation. Conclusions: Red beet fortified yogurt and inhibited the development of PD in mice better than levodopa drug, which may be partly responsible for decreased oxidative damage and enhances dopamine production in brain. Parkinson’s disease Rotenone Beetroot Yogurt levodopa and Behavioral tests Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 1. Introduction Neurodegenerative disorders pose a major global health burden, affecting millions of people worldwide and showing a notable rise in prevalence as life expectancy increases. Among the most prevalent of these conditions are Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis, multiple sclerosis, and Huntington’s disease [1].Parkinson's disease (PD) is a neurological disorder that worsens gradually over time, often affecting a person’s ability to move. Common symptoms are muscle rigidity, tremors, bradykinesia, and reduced motor balance [2].In recent years, the influence of intestinal microorganisms has become a growing focus of scientific investigation. An increasing number of studies have identified a link between gut microbiota 7 and constipation associated with PD[3, 4].As a result, conventional therapeutic approaches are increasingly being replaced by microecological strategies [5, 6]. Constipation may also hinder the absorption of anti-Parkinson’s medications, including levodopa [7]. Since ancient times, humans have depended on natural products as a fundamental source of therapeutic agents to manage various illnesses, disorders, and physical debilities. Experimental research has shown that these natural compounds possess multiple biological activities, including antioxidant, anti-inflammatory, and anti-apoptotic effects. Findings from both in vitro and in vivo studies have further confirmed their promising role in numerous preclinical models of neurodegenerative diseases[8, 9]. Beta vulgaris, widely recognized as beetroot, has been cited in traditional medicine for its neuroprotective potential in managing various CNS-related disorders. Reviews of the literature reveal that B. vulgaris exhibits several pharmacological properties, including antidepressant, antioxidant, anticonvulsant, cerebroprotective, and hepatoprotective effects[ 10 ] .Betanin, the primary constituent of red beetroot, highlights the therapeutic promise of beetroot and its bioactive compounds (betalains) as potential complementary treatments for multiple health conditions [ 11 ] .Structurally, betalains share a core betalamic acid unit linked to cyclo-dopa, which originates from L-dopa metabolism [ 12 ] . In addition to, the studies indicate that levodopa is naturally present in beetroot as an intermediate in the metabolic pathway for the formation of betalain pigments and has been identified using HPLC/MS analysis [ 13 ] . Yogurt contains live bacterial cultures, referred to as probiotics, which are well known for their positive effects on gastrointestinal function. These probiotics support intestinal microbial balance by stimulating the proliferation of beneficial bacteria and suppressing the growth of harmful species [14, 15].Preserving balance within the gut microbiota has been linked to better digestive function, increased nutrient uptake, and enhanced immune system efficiency [16, 17]. 2. Materials and Methods 2.1 Animals Adult male Swiss albino mice (25 ± 5 g) were used in this study, obtained from the National Research Centre (Giza, Egypt). They were housed in plastic cages under controlled conditions (23–25 °C, 40–60% humidity, 12-h light/dark cycle) with free access to food and water. 2.2 Drugs and Chemicals Rotenone and the vehicle (dimethyl sulfoxide; DMSO) were purchased from Sigma-Aldrich (St Louis, MO, USA). Levodopa- karpidopa (Sinemet drug) obtained from the Glopal Napi Pharmaceuticals company, Cairo, Egyp t. 2.3 Food Items Beetroot and yogurt were obtained from a local market in Cairo, Egypt. 2.4 Experimental Design Animals were randomly allocated into 5 groups (n = 7). Group1. Recieved the vehicle (DMSO1ml / mice, s.c 3 times / week for consecutive 3 weeks) and served as the negative control group. In the other 4 groups, mice received rotenone (1.5 mg/kg 3 times / week on days 1,3,5) for consecutive 3 weeks, s.c + basel diet [18]. Group2. (ROT) Received ROT (1.5 mg/kg 3 times / week for consecutive 3 weeks, s.c) and served as the positive control group. Group3. (ROT- Sinemet) Received ROT + Sinemet (100mg/kg b.wt./day p.o) daily for consecutive 3 we,eks [ 19 ] , as standard drug and served as standard treated group. Group4. (ROT - Beetroot) Received ROT + Beetroot extract 300 mg/kg b.wt./day p.o daily for consecutive 3 weeks [20] , and served as treated group. Group5. (ROT – Beetroot- Yogurt) Received ROT+ beetroot extract + Yogurt (10 ml / kg b.wt daily for consecutive 3 weeks [21] and served as treated group. Foods and drug treatments were administered one hour after the daily rotenone injections. Each mouse was weighed at the start of the study and then weekly until the experiment ended. Daily food intake was recorded, and treatments continued throughout the study. In the third week, behavioral tests were conducted, during which treatments were discontinued from the start of testing [22]. 2.5 Black Fecal Variables Feces excreted by mice during 2 h were collected after 7, 14, and 17 d of administration. Fecal number, weight, and water content were measured[ 21 ] . 2.6 Behavioral Tests 2.6.1 Rotarod test (RT) : the test was carried out in accordance with [23, 24]. 2.6.2 Balance beam walking (BBW) : the test was performed to[25, 26]. 2.6.3 Activity cage : the test was performed based on [ 27 ] . 2.6.4 Cylinder test : the test was performed as reported by [ 28 ]. 2.6.5 Forced swimming test : the test was performed according to[ 29 ] . 2.6.6 Catalepsy test : the test was performed based on[ 30 , 31 ] . 2.6.7 Tail suspension test: the test was performed as reported by[ 32 ] . 2.6.8 Hot plate : the test was carried out in accordance with, [ 33 , 34 ] . 2.7 Biochemical Evaluation on Mice Serum: 2.7.1 Determination of Liver Functions of Mice Serum: 2.7.1.1 Determination of Alanine aminotransferase (ALT)was according to FineTest CO, Catalogue No. EM0829. 2.7.1.2 Determination of Aspartate aminotransferase (AST) was according to FineTest CO , Catalogue No. EM0857. 2.7.2 Determination of Kidney Functions of Mice Serum: 2.7.2.1 Determination of Uric Acid was according to elabscience CO , Catalogue No. E-BC-K016-S. 2.7.2.2 Determination of Creatinine was according to BioVision’s CO , Catalog No. # K625-100. 2.7.2.3 Determination of Urea nitrogen was according to SunLong Biotech Co, LTD, Catalog No. SL0892Mo 2.8 Biochemical Evaluation of Mice Brain Tissues: 2.8.1 Oxidative Stress Biomarkers: 2.8.1.1 Determination of Malondialdehyde (MDA) ELISA Kit was according to life span bio sciences, inc CO, Catalog No. LS-F28474. 2.8.1.2 Determination of Glutathione (GSH) Assay Kit was according to biovision CO, Catalog No. # K464-100; 100. 2.8.1.3Determination of Nitric Oxide (NO) Assay Kit was according to Elabscience CO, Catalog No . E-BC-K035-M. 2.8.2 Neuroinflammation Biomarkers: 2.8.2.1 Determination of Tumor Necrosis Factor Αlpha, TNF-A ELISA Kit was according to Bioassay Technology laboratory. CO, Catalog No . E0117Mo. 2.8.2.2 Determination of Interleukin 6 IL-6 ELISA MAX™ was according to BioLegend’s. CO, Catalog. No. 431301. 2.8.2.3 Determination of Inducible nitric oxide synthase INOS ELISA Kit was according to Novus Biologicals a Biotechne Brand. CO, NBP2-80256. 2.8.3 Apoptotic Indices of Mice Brain Tissus 2.8.3.1 Determination of Caspase 3 (CASP 3) ELISA Kit was according to Novus Biologicals a Elabscience®. CO, Catalog. No. E-EL-M0238. 2.8.3.2 Determination of Alpha-synuclein (α-syn) ELISA Kit was according to Novus Biologicals a Biotechne Brand. CO, NBP3-08174. 2.8.3.3 Determination of Deoxyribonucleic acid DNA fragmentation was according to Zymoresearch Quick-gDNA™ MiniPrep kit . Catalog No. D3024. 2.8.4 Neurotransmitters of Mice Brain Tissus 2.8.4.1 Determination of Acetyl cholinesterase (ACHE) ELISA Kit was according to CUSABIO Catalog No. CSB-E17521m. 2.8.4.2 Determination of Tyrosine Hydroxylase (TH) ELISA Kit was according to Novus Biologicals a Biotechne Brand. CO, NBP3-06921 2.8.4.3 Determination of Dopamine ELISA Kit was according to CUSABIO Catalog No. CSB -E08661m. 2.8.5 Evaluation of α-syn on Mice Intestines Tissues Determination of Alpha-synuclein (α-syn) ELISA Kit was according to Novus Biologicals a Biotechne Brand. CO, NBP3-08174. 2.9 Fecal Variables Evaluation The moisture content of feces was evaluated by measuring the weight of freshly collected pellets, which were then dried at room temperature until a stable weight was obtained. The percentage of water content was calculated as: [(fresh weight − dry weight) / fresh weight] × 100 [35]. 3. Analysis of Statistical Data Data are presented as mean ± standard error of the mean (SEM). Differences between groups were evaluated using one-way ANOVA, followed by Tukey’s post hoc test for multiple comparisons [36]. Statistical analyses were conducted using GraphPad Prism (version 6, USA). Values of p < 0.05 were considered statistically significant. 4. Results 4.1 The Loco motor and Balance of Mice Parkinson’s disease (PD) is a chronic neurological disorder marked by nigrostriatal degeneration, muscle stiffness, resting tremors, slowed motor activity (bradykinesia), and difficulties with balance and posture[37] . The rotarod test is widely used in rodents to assess motor coordination, balance, and learning, as well as to detect neurological impairments. Modified versions improve the accuracy of preclinical drug and therapy evaluations [38]. Furthermore, the balance beam walking test serves as a functional approach to evaluate dynamic balance in experimental models [39]. The result present in (Figure.1) that the effect beetroot fortified yogurt as a natural source of levodopa compared to drug therapy on rotarod (Running time & Number of falls) and balance beam walking tests in male mice suffering from parkinson's disease. The result showed that the running time on the rotarod test for positive control group was much lower than negative control group. Even, there were statistical significan differences observed between them at ( P<0.05 ). At the same time, the number of falls on the rotarod test for positive control group was much higher than negative control group. Even, there were statistical significan differences observed between them at ( P<0.05 ). As for the time taken to cross the balance beam for positive control group was much higher than negative control group. Even, there were statistical significan differences observed between them at ( P<0.05 ). On the other hand, the treated group with sinemet drug for running time on the rotarod test was higher than positive control group and much lower than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). While, the mean value for number of falls on the rotarod test for sinemet drug group was lower than positive control group and much higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). In addition to, the mean value for time taken to cross the balance beam test for sinemet drug group was lower than positive control group and much higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). On contrast, the treated groups with beetroot as a natural source of levodopa and yogurt for running time on the rotarod test were much higher than positive control group. Even, there were statistical significant differences observed between them at ( P<0.05 ).As for the number of falls on rotarod test, the treated groups with beetroot as natural source of levodopa and yogurt were much lower than positive control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). Remarkably, the treated groups with beetroot as a natural source of levodopa and yogurt for running time and number of falls on rotarod test were approximately similar results as compared to negative control group. Even, there were no statistical significant differences observed between them at ( P<0.05 ). As regard, the treated groups with beetroot as a natural source of levodopa and yogurt for time taken to cross the bar in the balance beam test were much lower than positive control group. Even, there were statistical significant differences observed between them at ( P<0.05 ).But, the treated groups with beetroot as natural source of levodopa and yogurt for time taken to cross the bar in the balance beam test were approximately similar results as compared to negative control group. Even, there were no statistical significant differences observed between them at ( P<0.05 ). 4.2 Spontaneous Locomotor Activity of Mice The cylinder test is used to evaluate a rat’s independent use of its forelimbs for supporting its body against the interior walls of a cylindrical chamber [ 40 ] .In addition, activity cages provide a practical method for monitoring spontaneous coordinated movements in both rats and mice whether tested individually or in groups as well as tracking changes in this activity over time [ 41 ] . The data in (Figures. 2) that the effect beetroot fortified yogurt as a natural source of levodopa compared to drug therapy on cylinder and activity cage tests in male mice suffering from Parkinson's disease. The data illustrated showed that the positive control group for cylinder and activity cage tests were much lower than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). While, the treated group with sinemet drug for cylinder and activity cage test was higher than positive control group. But still much lower than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). Conversely, the treated groups with beetroot as a natural source of levodopa and yogurt for cylinder and activity cage tests were much higher than positive control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). While, the treated group with beetroot plus yogurt for cylinder and activity cage tests were approximately normalize as compared to negative control group. Even, there were no statistical significant differences observed between them at ( P<0.05 ).But, the treated group with beetroot still lower than negative control group. The best result was the group treated with beetroot as a natural source of levodopa plus yogurt. This group outperformed their counterpart who received the same beetroot as a natural source without yogurt. 4.3 Depression, Catalepsy , and Sensation of Mice The forced swim test relies on the observation that when rodents are placed in an unavoidable and aversive environment, they adopt different coping strategies, which can be classified as either active or passive responses [ 42 ] .Similarly, the tail suspension test (TST) is employed to evaluate depressive-like behaviors in animals; in this method, mice suspended by their tails exhibit periods of immobility, interpreted as an indication of behavioral despair [ 32 , 43 ] .The catalepsy bar test is a common approach for assessing an animal’s inability to correct an externally imposed posture, typically resulting from muscular rigidity [ 44 ] . Furthermore, the hot plate test (HPT) in a dynamic setting is used to measure thermal nociception in rats by evaluating central mechanisms and determining the thermal nociceptive threshold [ 45 ] . The result present in (Figure.3) that the effect beetroot fortified yogurt as a natural source of levodopa compared to drug therapy on some behavior tests such as forced swim, tail suspension, catalepsy and hot plate in male mice suffering from parkinson's disease. The result showed that the positive control group for forced swim test was much lower than negative control group. Even, there were statistical significan differences observed between them at ( P<0.05 ). While, the mean values for positive control group in tail suspension, catalepsy and hot plate tests were much higher than negative control group. Even, there were statistical significan differences observed between them at ( P<0.05 ). On contrast, the treated group with sinemet drug for forced swim test was higher than positive control group but still much lower than negative control groups. Even, there were statistical significant differences observed between them at ( P<0.05 ). While, the means value for sinemet drug group in tail suspension, catalepsy and hot plate tests were lower than positive control group and much higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). As regarded, the treated groups with beetroot as a natural source of levodopa and yogurt in forced swim test were much higher than positive control group. Even, there were statistical significant differences observed between them at ( P<0.05 ).While, the treated groups with beetroot as natural source of levodopa and yogurt in tail suspension, catalepsy and hot plate tests were much lower than positive control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). Remarkably, all treated groups with natural source of levodopa and yogurt in forced swim, tail suspension, catalepsy and hot plate tests were approximately normalize as compared negative control group. Even, there were no statistical significant differences observed between them at ( P<0.05 ). 4.4 Liver Functions of Mice Serum exposure to toxicants and impaired liver detoxification can increase susceptibility to Parkinson’s disease, as liver dysfunction may lead to neurological complications including parkinsonism [46, 47]. The result illustrated in (Figure.4) that effect beetroot fortified yogurt as a natural source of levodopa compared to drug therapy on liver functions such as alanine amino transferase (ALT) and aspartate amino transferase (AST) in male mice suffering from parkinson's disease.The result illustrated showed that ALT and AST levels for positive control group were much higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). On the other hand, observed that the sinemet drug group of ALT and AST levels was lower than positive control group and still much higher than negative control group. Even, there were statistical significant differences observed between them at (P<0.05). As regard, the treated group with beetroot as a natural source of levodopa plus yogurt and counterpart without yogurt of ALT and AST were much lower than positive control group. Even, there were statistical significant differences observed between them at (P<0.05). But, the treated group with beetroot as a natural source of levodopa plus yogurt it has approximately similar result as compared to negative control group. Even, there were no statistical significant differences observed between them at (P<0.05).While, the treated group with beetroot as a natural source of levodopa without yogurt did not same affect. 4.5 Renal Functions of Mice Serum Evidence shows that even early renal disease is linked to cognitive decline, depression, and motor disturbances. CKD-related toxins and metabolic syndrome can impair dopaminergic neurons, while kidney-derived hormones like vitamin D provide neuroprotection [48]. The result present in (Figure.5) that the effect beetroot fortified yogurt as natural source of levodopa compared to drug therapy on renal functions such as urea nitrogen, creatinine and uric acid in male mice suffering from parkinson's disease. The result showed that the urea nitrogen, creatinine and uric acid levels in serum male mouse for positive control group were much higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). Whereas, the data illustrated showed that the urea nitrogen, creatinine and uric acid levels for sinemet drug group were lower than positive control group. But, still much higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). On contrast, all treated groups with beetroot as a natural source of levodopa and yogurt for urea nitrogen, creatinine and uric acid levels were much lower than positive control group. Even, there were statistical significant differences observed between them at ( P<0.05 ).But, the treated groups with beetroot as a natural source of levodopa plus yogurt was has approximately normal level of urea nitrogen , creatinine and uric acid as compared to negative control group. Even, there were no statistical significant differences observed between them at ( P<0.05 ). While, treated group with beetroot still higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). Moreover, the result showed that the treated group with beetroot has approximately similar result as compared to sinemet drug group for uric acid level. Even, there were no statistical significant differences observed between them at ( P<0.05 ). 4.6 Oxidative Stress of Mice Brain Tissue Recent research shows that neuronal death can occur via multiple mechanisms, with oxidative stress indicated by MDA, GSH, and NO-being a major contributor [49]. The data illustrated in (Figure.6) that effect beetroot fortified yogurt as a natural source of levodopa compared to drug therapy on Oxidative Stress Biomarkers such as Malondialdehyde (MDA), Nitric oxide (NO) and Glutathione (GSH) in male mice suffering from parkinson's disease.The data illustrated showed that the oxidative stress biomarker such as MDA and NO levels in brain tissue for positive control group were much higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). But , the level of GSH in brain tissue for positive control group was much lower than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). whereas, the treated group with sinemet drug for MDA and NO levels was lower than positive control group and much higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). Moreover, the treated group with sinemet drug for GSH level was much higher than positive control group. But, still lower than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). On contrast, the treated groups with beetroot as a natural source of levodopa and yogurt for MDA and NO levels were lower than positive control group. But, the treated group with beetroot as a natural source of levodopa without yogurt still higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). While, the treated groups with beetroot plus yogurt has approximately similar result as compared to negative control group. Even, there was no statistical significant differences observed between them at ( P<0.05 ). Conversely, the data illustrated showed that GSH for the treated groups with beetroot as a natural source of levodopa and yogurt were much higher than positive control group. But, the treated group with beetroot without yogurt still lower than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ) . While, treated group with beetroot plus yogurt was has approximately normal level of GSH as compared to negative control group. Even, there were no statistical significant differences observed between them at ( P<0.05 ) . Unlike the groups treated with beetroot as a natural source of levodopa without yogurt, it didn't give the same effect. Moreover, the treated groups with beetroot as a natural source of levodopa has approximately similar result as compared to sinemet drug group in NO and GSH levels. Even, there were no statistical significant differences observed between them at ( P<0.05 ). 4.7 Neurotransmitters of Mice Brain Tissu Parkinson’s disease is a progressive neurodegenerative disorder caused by the loss of dopamine-producing neurons in the substantia nigra [50]. The data illustrated in (Figure.7) that the effect beetroot fortified yogurt as a natural source of Levodopacompared to drug therapy on neurotransmitters such as Ty,rosine hydroxylase (TH), Dopamine (DOPA) and Acetylcholinesterase (ACHE) in brain tissue male mice suffering from parkinson's disease.The data illustrated showed that the neurotransmitters such as TH, DOPA and ACHE levels in brain tissue for positive control group were much lower than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). While, the treated group with sinemet drug for TH, DOPA and ACHE level was higher than positive control group and much lower than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). On contrast, all treated groups with beetroot as a natural source of levodopa and yogurt for TH, DOPA and ACHE levels were much higher than positive control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). As regard, the treated group with beetroot as a natural source of levodopa plus yogurt was has approximately similar result as compared to negative control groups. Even, there were no statistical significant differences observed between them at ( P<0.05 ). While, the treated group with beetroot as a natural source of levodopa without yogurt still lower than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). 4.8 Apoptotic Indices of Mice Brain Tissu Apoptosis is a programmed cell death process, with mitochondria playing a key role; reduced mitochondrial membrane permeability is an early event in this pathway [51]. The data illustrated in (Figure.8) that the effect beetroot fortified yogurt as a natural source of Levodopacompared to drug therapy on apoptotic indices such as deoxyribonucleic acid (DNA), caspase-3 (Casp-3) and α-synuclein (α-syn) in brain tissue male mice suffering from parkinson's disease.The data illustrated showed that DNA level for positive control group was much lower than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). While, the Casp-3 and α-syn levels in brain tissue for positive control group were much higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). On the other hand, the treated group with sinemet drug for DNA level was higher than positive control group and much lower than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ).But, the treated group with sinemet drug for Casp-3 and α-syn levels were lower than positive control group and much higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). Concerning, the treated groups with beetroot as a natural source of levodopa and yogurt for DNA level were much higher than positive control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). But, the treated group with beetroot as a natural source of levodopa without yogurt still lower than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). While, surprisingly, the treated group with beetroot plus yogurt responded in a comparable way as compared to negative control group. Even, there were no statistical significant differences observed between them at ( P<0.05 ). As for the other parameters, such as Casp-3 and α-syn levels, the treated groups with beetroot as a natural source of levodopa and yogurt were much lower than positive control groups. Even, there were statistical significant differences observed between them at ( P<0.05 ).However, the treated group with beetroot as a natural source of levodopa without yogurt still higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). While, the treated group with beetroot plus yogurt has approximately similar result as compared to negative control groups so alike, almost as if the induction with rotenone had no impact at all. Even, there were no statistical significant differences observed between them at ( P<0.05 ). Inflammatory Indices of Mice Brain Tissue 4.9 Neuroinflammation, a CNS defense mechanism, involves overactivation of neurons and glial cells, releasing markers like TNF-α, IL-1β, IL-10, NO, and COX-2, which contribute to the onset, diagnosis, and treatment of neurodegenerative diseases [52] . The result present in (Figure.9) the effect beetroot fortified yogurt as a natural source of Levodopa compared to drug therapy on Inflammatory indices such as tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (Inos) and interleukin-6 (IL-6) in brain tissue male mice suffering from parkinson's disease.The result illustrated showed that the inflammatory indices such as TNF-α, Inos and IL-6 levels in brain tissue for positive control group were much higher than negative control group. Even, there were statistical significan differences observed between them at ( P<0.05 ). In relation to, the treated group with sinemet drug for TNF-α, Inos and IL-6 levels were lower than positive control group and much higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). Whereas, the treated groups with beetroot as a natural source of levodopa and yogurt for TNF-α, Inos and IL-6 levels were much lower than positive control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). But, the treated group with beetroot as a natural source of levodopa without yogurt still higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). While, it turns out the treated group with beetroot plus yogurt has approximately similar result as compared to negative control groups. Even, there were no statistical significant differences observed between them at ( P<0.05 ), which is interesting. As also the results showed, the treated group with beetroot has approximately similar result as compared to treated group with sinemet drug .Even, there were no statistical significant differences observed between them at ( P<0.05 ). Apoptotic Indices α- Synuclein of Mice Intestines 4.10 Importantly, α-Synuclein accumulation in the substantia nigra underlies motor impairments in PD, while non-motor symptoms, often affecting the gastrointestinal tract, can appear years earlier and may be linked to α-Syn aggregates in the GIT [53]. The data illustrated in (Figure.10) the effect beetroot fortified yogurt as a natural source of Levodopacompared to drug therapy yogurt and drug therapy on apoptotic indices α- Synuclein (α-syn) in intestines tissue male mice suffering from parkinson's disease. The data illustrated showed that the positive control for α-syn level in intestines tissues group was much higher than negative control group. Even, there were statistical significan differences observed between them at ( P<0.05 ). on contrast, the treated group with sinemet drug for intestines α-syn level was lower than positive control group. But, still much higher than negative control groups. Even, there were statistical significant differences observed between them at ( P<0.05 ). On contrast, the treated groups with beetroot as a natural source of levodopa and yogurt for intestines α-syn level were much lower than positive control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). But, the treated group with beetroot as a natural source of levodopa without yogurt still higher than negative control group. Even, there were statistical significant differences observed between them at ( P<0.05 ). While, the treated group with beetroot plus yogurt has approximately similar result as compared to negative control group. Even, there were no statistical significant differences observed between them at ( P<0.05 ). 4.11 Constipation of Mice Recent studies suggest that intestinal microbial dysbiosis contributes to constipation by altering gut flora[15] Such dysbiosis can also impair the absorption of Parkinson’s disease medications, including levodopa [54]. The data illustrated in Table (2) that the effect beetroot fortified Yogurt as a natural source of levodopacompared to drug therapy on Number, weight (g) and water content (%) in fecal male mice suffering from parkinson's disease. The data illustrated showed that the fecal number, weight and water content of the positive control group were significantly lower than negative control group. These values began to gradually decline when measured after 7, 14, and 21 days, reflecting the severity of constipation in this group. However, these differences were not statistically significant at p < 0.05 . On contrast, the treated group with sinemet drug for fecal number was lower than positive control group and negative control group when measured after 7, 14, and 21 days. Although the number of fecal pellets decreased compared to the positive control group. But, don’t have statistically significant differences observed at p < 0.05 . As regard, the treated groups with beetroot as a natural source of levodopa and yogurt for fecal number, The results were striking when measured at 7, 14 and 21 days, as some groups had fewer stools than the negative control group, and some recorded the same level of fecal count. However, it was interesting that there were groups that recorded a higher number, but the treated groups were still lower than the negative control group. But, don’t have statistically significant differences observed at p < 0.05 . Table (1): Effect Beet root Fortified Yogurt as a Natural Source of Levodopa on Number, Weight (g) and Water content (%) in Fecal Male Mouse Enhance in Rotenone Induced Parkinson's Disease Values are expressed as mean ± SE (n =6 ). 5. Discussion Nutritional interventions are increasingly utilized in managing neurodegenerative disorders and may help alleviate symptoms associated with Parkinson’s disease and enhance general health. Beetroot, as a natural source of levodopa, represents a promising dietary component that could support dopaminergic function and contribute to better disease management. Compared with conventional drug therapy, such an approach may offer symptomatic relief with fewer side effects. In the current study, the increasing in number of falls and decreasing in running time for rotarod and time taken to cross the balance beam reduction for positive control group as compared with other control group. It may be due to injection with rotenone, which led to impaired coordination and balance, which are common symptoms of Parkinson's disease. The longer time it took them to cross the balance beam indicates difficulty moving and poor muscle control, reflecting the motor dysfunction associated with Parkinson's disease.To further support this explanation, it is very important to clarify these results in the light of previous findings. Several risk factors, including age, head injury, genetic predisposition, and exposure to toxins, contribute to the progression of Parkinson’s disease (PD) [55].Dopamine depletion results in motor impairments, including resting tremor, bradykinesia, postural instability, and muscle rigidity[56]. These results agreed with Makav & Eroğlu [57] study whom reported that the rotarod test showed significant differences in mean running times among the groups (P < 0.05). Daily oral administration of Sinemet improved movement and balance.This result agreed with Perez-Pardo et al. [58],study whom reported that rotenone injection significantly reduced rotarod performance and grip strength in mice, while levodopa improved these outcomes. In contrast, beetroot extract with yogurt produced greater benefits, enhancing dopamine levels and leading to superior improvements in rotarod and balance beam tests.These results agreed with Leroy et al. [59], study whom reported that this review and preliminary meta-analysis demonstrated that oral levodopa markedly enhanced performance in clinical balance assessments, such as the Berg Balance Scale (BBS) and the Postural Reaction Test (PRT), with non-significant positive trends in other tests.Also, Kwankaew et al. [60], study whom reported that betanin from red beet extract restored the impaired motor performance caused by CCI surgery in mice, as confirmed by rotarod testing compared to controls.In addition to, Zhao et al. [61], study whom reported that FMT-treated mice showed significant improvements in motor function, as reflected by better performance in the rotarod test (P < 0.001), adhesive removal test (P < 0.001), grip strength test (P < 0.01), and pole test (P < 0.001) compared to the rotenone-treated group (Fig.1). Furthermore, rotenone injection resulted in noticeable motor impairment.These results reflected in a reduced use of the forelimbs during the cylinder test and a decline in spontaneous activity cage test. These observations suggest that rotenone may negatively affect dopaminergic pathways, leading to deficits in motor coordination and exploratory behavior, reflecting the motor dysfunction associated with Parkinson's disease. These results agreed with Avcı et al. [62] , study whom reported that rotenone significantly impaired motor coordination and balance in the cylinder test, while daily Sinemet treatment improved these functions.These results agreed with Gellhaar et al. [63], study whom reported that long-term L-DOPA led to abnormal repetitive behaviors in MitoPark mice, while natural levodopa with yogurt showed more stable benefits, enhancing forelimb use and exploration in cylinder and activity cage tests. These results agreed with ElSayed et al. [64], study whom reported that the high-dose betanin improved locomotor activity and alleviated rotenone-induced incoordination, leading to better motor function in the PD model. Kim et al. [ 65 ] , study whom reported that the probiotic intake significantly improved motor function (p < 0.05), as confirmed by one-way ANOVA and independent t-test analyses (Fig.2). It is noteworthy that the observed reduction in locomoter activity, along with increased immobility, hypo-responsiveness, apathy, Loss of sensation of heat and prolonged catalepsy duration, may strongly suggest that rotenone injection is reponsaible for these behavioral impairments. This was confirmed by the results of the forced swim, tail suspension, hot plate, and catalepsy tests.These results align with previous studies demonstrating that the neurotoxic effects of rotenone induce Parkinson’s-like symptoms through mitochondrial complex inhibition and the promotion of oxidative stress.Such behavioral alterations reflect the neurodegenerative impact of rotenone on dopaminergic pathways particularly in the substantia nigra. This is one of common symptoms of parkinsons disease, known as non- motor symptoms. Consistent with a study on 109 newly diagnosed, untreated patients, non-motor symptoms such as apathy, sleep disturbances, daytime sleepiness, and constipation were reported in 60–70% of cases before diagnosis, occurring more frequently than in controls. Other early symptoms included anhedonia, memory issues, sensory loss, mood changes, sweating, fatigue, pain, and gastrointestinal problems, some of which appeared over a decade before motor onset [66] . Symptoms of depression and anxiety may appear well in advance of the actual diagnosis. [67].Moreover, Ahmed et al. [68] , study whom reported that the Depressive-like behaviors in rotenone-treated rats were assessed by FST, TST, catalepsy, and hot plate tests, showing significantly longer immobility times (p<0.001) versus controls. Daily Sinemet treatment improved motor coordination and balance.These results agreed with Luthra et al. [69] , study whom reported that haloperidol-induced PD models showed motor and behavioral deficits measured by catalepsy, hot plate, and swim tests. While L-DOPA provided some recovery, beetroot extract with yogurt was more effective, enhancing dopamine, improving motor function, and reducing anxiety and stiffness, as confirmed by multiple behavioral tests. These results agreed with Sulakhiya et al . [70] , study whom reported that to assess the effect of BVEE on ARS-induced depressive-like behavior, immobility time in the FST was measured. ARS significantly increased immobility (p<0.001), confirming its depressive effect, while BVEE pretreatment markedly reduced this response (p<0.05; p<0.01 at 200 mg/kg).Moreover, Sulakhiya et al . [ 70 ] , study whom reported that mice exposed to ARS showed a marked rise in immobility time in the TST (p<0.001), while BVEE pretreatment significantly reversed this effect at 100 mg/kg (p<0.05) and 200 mg/kg (p<0.01), demonstrating its protective role.In addition to, Liu et al. [71], study whom reported that restraint stress induced depressive-like behaviors and gut microbiota alterations in mice, while probiotic treatment restored microbial balance and alleviated these effects, leading to improved outcomes in FST, TST, catalepsy, and hot plate tests (Fig.3). Evalution of liver function markers provides insight into systemic effects associated with Parkinson’s disease in experimental models. In this context, the resuts showed that increased in ALT and AST reduction for positive control group as compared to other control groups. It may be due to, injection with rotenone which increase Parkinson's symptoms in mice. These results agreed with studies indicate that liver disease–related parkinsonism may result from mechanisms such as metal overload, hyperammonemia, oxidative stress, disrupted glia-neuron balance, and neurotransmitter changes, which collectively contribute to dopaminergic neuron loss in PD [72].In addition to, Wang et al. [73] , study whom reported that "Rotenone markedly elevated hepatic index and serum AST and ALT, and caused hepatocyte structural damage. Oral Sinemet provided only slight improvement in liver function.In this context, these results agreed with Kura et al. [74], study whom reported that serum biochemical analysis (ALT, AST, ALP, GGT) confirmed liver function. AST was slightly higher in levodopa-treated mice, though not significantly different from controls. In contrast, beetroot as a natural levodopa source combined with yogurt showed greater positive effects on liver function than Sinemet in PD mice.These results agreed with Gashash & Wahba [ 75 ] study whom reported that the findings showed Rats receiving a diet enriched with beetroot juice showed a significant decrease (P < 0.05) in ALT and AST levels relative to the control group. Moreover, Hasan et al. [76, 77] , study whom reported that ALT and AST are key markers for diagnosing NAFLD, and their levels decreased with yogurt supplementation. This effect may relate to probiotic activity that normalizes liver enzymes, reduces intestinal and hepatic inflammation, and protects against liver injury (Fig.4). As regard, the increasing in urea nitrogen, creatinine and uric acid reduction for positive control group as compared to control groups. It may be due to, injection with rotenone which increase Parkinson's disease. These results agreed with Udeani et al. [ 78 ] , study whom reported that repeated intragastric rotenone administration caused kidney damage, evidenced by elevated BUN, uric acid, and creatinine levels. Moreover, Juli et al. [79] , study whom reported thatrotenone significantly elevated kidney function markers, including urea (p<0.05) and creatinine (p<0.001), compared to controls. Sinemet treatment showed only mild improvement in these parameters. In addition to,the best result was the treated group with beetroot as a natural source of levodopa plus yogurt more than counterpart without yogurt did not give the same affect. Notably, the beetroot as a natural source of levodopa and yogurt can positively enhance renal functions better than the levodopa drug (sinemet) in the serum of mice suffering from Parkinson's disease. These results agreed with Gashash & Wahba [75]study whom reported dietary supplementation with beetroot juice resulted in a significant reduction (P < 0.05) in serum urea, creatinine, and uric acid levels in rats compared with the positive control group.In addition to, Cheng et al. [80] , study whom reported that yogurt significantly (p<0.05) lowered urinary protein, serum creatinine, and BUN levels in nephritic mice compared to controls (Fig.5). The current findings on oxidative stress markers provide insight into the biochemical changes linked to Parkinson’s disease in the experimental group were evaluated.The increasing in NO and MDA and reduction in GSH for positive control group as compared with other control groups. It may be due to injection with rotenone which increases Parkinson's disease. These results agreed with studies have shown that lifestyle and environmental factors, such as exposure to pesticides and contact with heavy metals, contribute to one in five cases of Parkinson's disease, which can have a detrimental effect on oxidative stress levels in brain tissue[81] . And , Abdel-Salam et al. [82] , studywhom reported that rotenone treatment increased brain MDA and NO while depleting GSH, whereas oral Sinemet improved these oxidative stress markers in PD mice.These results agreed with Ayaz et al. [83] , study whom reported that the rotenone elevated brain MDA and NO and reduced GSH, while Sinemet partially restored these levels in PD mice. On contrast, It was observed that the group suffering from Parkinson's disease and treated with beetroot as a natural source of levodopa plus yogurt have best result for MDA and NO as compared to counterpart without yogurt. This result mean that, the beetroot as a natural source of levodopa and yogurt have beneficial therapeutic effect better than sinemet drug on oxidative stress markers in the tissue of mice with Parkinson's disease. These results agreed with Sushama et al. [ 84 ] , study whom reported that our findings support that natural levodopa sources deliver L-DOPA to the brain more effectively and sustainably than conventional antiparkinsonian drugs.Moreover, Thong-Asa et al. [ 85 ] , study whom reported that betanin extracted from red beet significantly reduced MDA levels and enhanced GSH activity (p < 0.05), demonstrating neuroprotective effects against rotenone-induced Parkinson’s disease in mice through its potent antioxidant action (Fig.6). The chemical evaluation of neurotransmitter levels highlights the harmful effects resulting from exposure to toxins on brain neurochemistry in mice suffering with Parkinson’s disease. The decreasing in TH, DOPA and ACHE reduction in positive control group as compared with other control groups. It may be due to, injection with rotenone which increase parkinson's disease. These results agreed with Abdel-Salam et al . [ 86 ] , study whom reported that the rotenone administration resulted in a significant 57.0% reduction .in striatal tyrosine hydroxylase levels relative to the vehicle-treated control group.Moreover, Landau et al. [ 87 ] , study whom reported that the rotenone reduced locomotor activity, lowered brain dopamine levels, and decreased vesicular sequestration indices (DOPAC/dopamine) compared to controls. In addition to, Hasan et al. [ 88 ] , study whom reported that the rotenone markedly decreased AChE activity in the cerebellum (p<0.05), whereas oral Sinemet improved neurotransmitter balance by elevating DOPA, AChE, and TH levels. While, administration of the oral sinemet treatment led to an improvement in the levels of DOPA, Ache, and TH.These results agreed with Chen et al. [ 89 ] , study whom reported that L-DOPA increased TH expression in SN and STR. On contrast, It was observed that, the groups suffering from Parkinson's disease and treated with beetroot as a natural source of levodopa plus yogurt has best result for TH, DOPA and ACHE as compared with its counterpart without yogurt.This result reflected that natural beetroot as a source of levodopa and yogurt has a positive therapeutic effect better than sinemet drug on neurotransmitters in brain tissue of mice with Parkinson's disease. These results agreed with Ghanbari et al . [ 90 ] , study whom reported that the dopamine receptor gene expression in the hippocampus was significantly elevated (p≤0.001, p≤0.01) in the beetroot juice and HIIT groups versus the diabetic control, with further increases (p≤0.001) observed in the combined HIIT + beetroot group. Moreover, Olasehinde et al. [ 91 ] , study whom reported that BR improved an increase ACE activities were observed in the brain of rats compared control group. In addition to, Hsieh et al. [92] , study whom reported that the daily probiotic supplementation markedly enhanced gait, balance, and coordination compared with the sham group, while maintaining TH-positive cells in the substantia nigra. These results suggest that prolonged probiotic intake protects dopaminergic neurons and mitigates motor impairments in MitoPark PD mice (Fig.7). Evaluation of DNA integrity, Caspase-3, and α-synuclein levels highlights the cellular damage and apoptosis associated with Parkinson’s disease in mice.The decreasing in DNA and increasing in Casp-3 and α-syn reduction in positive control group as compared with other control groups. It may be due to, injection with rotenone which increase Parkinson's disease. These results agreed with Balakrishnan et al. [ 93 ] , study whom reported that the chronic rotenone administration induced PD-like pathology, marked by oxidative stress, elevated α-synuclein, and increased expression of apoptotic proteins caspase-3, -8, and -9.Moreover, Khalil et al. [ 94 ] , study whom reported that the rotenone-treated mice exhibited elevated TNF-α, IL-1β, DNA damage, and caspase-3 expression, while oral Sinemet improved DNA integrity, Casp-3, and α-synuclein levels, alleviating PD symptoms.These results agreed with Motawi et al. [ 95 ] , study whom reported thatSinemet significantly reduced caspase-3 fragmentation and α-synuclein levels (p<0.0001) compared to rotenone, showing approximately 70% improvement in these markers.On contrast, It was observed that the groups suffering from Parkinson's disease and treated with beetroot as a natural source of levodopa plus yogurt has best result for DNA, Casp-3 and α-syn as compared to its counterpart without yogurt.This results reflected that, the beetroot as a natural source of levodopa and yogurt have a positive therapeutic effect better than sinemet drug on apoptotic indices in brain tissue of mice with Parkinson's disease. These results agreed with Phukan et al. [ 96 ] , studywhom reported that the red beetroot extract, rich in betanin, reduced abnormal α‑synuclein accumulation in dopaminergic neurons of PD mice.Also, Wang et al. [ 97 ] , study whom reported that our results indicated that probiotics of L. plantarum DP189 reduced the α-SYN accumulation in SNin brain mice in comparison with control group ( p < 0.05) (Fig.8). Moreover, the resuts showed that the increased in TNF-α, Inos and IL-6 levels reduction in positive control group as compared with other control groups. It may be due to, injection with rotenone which increase parkinson's disease. These results agreed with Siracusa et al. [ 22 ] , study whom reported that iNOS expression in the SN was significantly increased 28 days after rotenone administration compared to controls.Moreover, Zhang et al. [ 98 ] , study whom reported that the rotenone significantly increased pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, IFN-γ, PGE2) and NO in the SN (p<0.01), while arctigenin was assessed for its effect on this neuroinflammation.On the other hand, administration of oral sinemet treatment resulted in a noticeable reduction in the levels of TNF-α, iNOS, and IL-6, indicating an attenuation of neuroinflammatory responses in Parkinson’s disease.These results agreed with Motawi et al. [ 95 ] , study whom reported that the regarding to IL-6 level showed significant decrease with sinemet (each P < 0.0001) treatments as compared with the rotenone group. Moreover, Abdel-Sattar et al. [ 99 ] , study whom reported that the mice treated with L-Dopa/carbidopa showed low levels of the inflammatory markers TNF-α, NF-κB and IL-1β in the striatum compared with rotenone group.The observed results allowed us to simply conclude that groups suffering from Parkinson's disease and treated with beetroot as a natural source of levodopa plus yogurt showed the best outcomes for TNF-α, iNOS, and IL-6 compared to its counterpart without yogurt.It reflected that, natural source of levodopa and yogurt have a positive therapeutic effect better than sinemet drug on inflammatory cytokines in brain tissue of mice with Parkinson's disease. These result agree with Khan et al. [ 100 ] , study whom reported that the negative control group showed a significant rise (P < 0.0001) in brain inflammatory cytokines compared to normal controls. Conversely, betalains and chloroquine groups exhibited a marked reduction (P < 0.0001), with the betalains protective group restoring cytokine levels toward normal values.In addition to, Ano et al. [ 101 ] , study whom reported that extracts from the surface of fermented dairy products suppressed microglial TNF-α production in a dose-dependent manner, enhancing anti-inflammatory activity and Aβ phagocytosis, whereas extracts from the interior or unfermented products had no effect (Fig.9). The present observations regarding α-synuclein accumulation highlight the potential involvement of the gut–brain axis in the development of Parkinson’s disease.This result supported the It may be due to, injection with rotenone leads tothe presence of pathogenic α-syn in both the gut and brain highlights the possible contribution of the enteric nervous system (ENS) to the etiology of PD. The hypothesis that α-syn pathology may propagate from the gut to the brain, leading to degeneration of the nigrostriatal dopaminergic pathway, remains highly compelling.These result agreed with Chen et al. [ 102 ] , study whom reported that the rotenone significantly increased intestinal α‑syn levels in hα‑syn+/– mice, showing a 2.3-fold rise at 6 months and a 2-fold rise at 12 months compared to age-matched controls. Moreover, administration of oral sinemet treatment appeared to mitigate α-synuclein accumulation, suggesting its potential in modulating the gut–brain axis and reducing neurodegeneration in Parkinson’s disease. This improvement indicates that sinemet treatment can partially counteract the effects of rotenone-induced pathogenic α-syn in both the gut and brain mice. These results agreed with Pellegrini et al. [ 103 ] , studywhom reported that the L-DOPA/BE treatment improved colonic motor activity and normalized immunopositivity, with beetroot plus yogurt showing the greatest reduction in intestinal α‑syn in PD mice compared to beetroot alone.Subsequently, it is reflected that, beetroot as a natural source of levodopa has a positive therapeutic effect better than sinemet drug on apoptotic indices such as α- synuclein in intestines tissue of mice with Parkinson's disease. These results agreed with Ko et al. [ 104 ] , study whom reported that the red beet RP and BP altered gut microbiota composition and SCFA production differently across enterotypes, with the Bifidobacterium cluster showing significantly reduced alpha diversity and distinct microbial changes.In addition to, Perazza et al. [ 105 ] , study whom reported that shannon index and PCoA analyses showed that dairy fermentation significantly modulated gut microbiota, with WT and LRKO mice fed fermented products exhibiting distinct α‑diversity and metagenomic profiles compared to nonfermented diets(Fig.10) . Regarding gastrointestinal function, the results showed that the positive control group showed significantly reduced fecal count, weight, and water content compared with the negative control group.Quite simply, it can be said that this occurred due to rotenone injection, which caused constipation in mice with Parkinson's disease, thereby contributing to impaired dopamine production and, consequently, reduced motor activity. These results were approximately agreed with Chu et al. [106] , study whom reported that rotenone intake led to a significant reduction in fecal pellet weight and water content compared with the control group in PD mice ( p < 0.05). During the treatment period, a marked change in stool shape was observed, from separate pellets to more compact, sometimes elongated, ribbon-like masses. This change in shape led to a decrease in the number of counted pellets. While, fecal weight and water content were higher than positive control group and much lower than negative control groups.These reflected that for sinemet drug group began to gradually increase when measured after 7, 14, and 21 days. This indicates that levodopa had a weak effect in improving the symptoms of constipation. However, these differences were not statistically significant at p < 0.05 . These result was approximately agreed with Radisavljevic et al. [ 107 ] , study whom reported that chronic oral L-DOPA plus carbidopa (LDCD) treatment reduced whole-gut transit time (p<0.0001), alleviating constipation-like symptoms in mice.On contrast, the number of fecal pellets decreased as compared to the positive control group, this is not necessarily indicative of worsening constipation. During the treatment period, a marked change in stool form was observed, from separate pellets to denser clumps. Sometimes longer, ribbon-like. This change in shape resulted in a decrease in the number of counted granules. This change is likely related to the effect of various natural sources of levodopa and yogurt, which improve fecal consistency and increase its viscosity, resulting in a less disintegrated and more cohesive fecal, a positive sign in the treatment of constipation. Thus, there is no exacerbation of Parkinson's disease symptoms as compared with the fecal weight and water content. But, without statistical significance. At the same time, fecal weight and water content were much higher than positive control group. And lower than negative control group. These mean , s that the treated groups with beetroot as a natural source of levodopa and yogurt began to gradually increase gradually and significantly when measured after 7, 14, and 21 days. Altogether, it was observed that, groups suffering from Parkinson's disease and treated with beetroot plus yogurt has best result for water content and fecal weight as compared to it is counterpart without yogurt. Subsequently, it was reflected that the beetroot as a natural source of levodopa and yogurt have a positive therapeutic effect better than sinemet drug for fecal weight and water content of mice with Parkinson's disease. These results were approximately agreed with Zhao et al. [ 61 ] , study whom reported that the rotenone caused weight loss, motor deficits, and GI dysfunction in mice, while FMT treatment significantly improved fecal output and alleviated these PD-related symptoms.Also, Mahran et al. [ 53 ] , study whom reported thatexperimental diets, especially PBM, significantly (p≤0.05) normalized constipation-related parameters in rats without causing diarrhea, supporting the traditional use of PP and BP for LOP-induced constipation (Table.1). 6. Conclusion Beetroot-fortified yogurt, as a natural source of levodopa, showed superior effects compared to conventional drug treatment, by enhancing brain dopaminergic neurons and improving motor symptoms in Parkinson’s-induced mice.Moreover, its antioxidant properties provided additional neuroprotection and symptom relief. These findings indicate that yogurt enriched with beetroot has the potential to be developed as a safe functional product, and cost-effective dietary strategy for Parkinson’s disease management. Abbreviations PD: Parkinson's disease; ROT: Rotenone; DMSO: dimethyl sulfoxide;L-DOPA:Levodopa; ALT:alanine aminotransferase; AST: aspartate aminotransferase; MDA: Malondialdehyde; GSH: Glutathione; NO: Nitric Oxide;TNF: Tumor Necrosis Factor Αlpha; IL-6: Interleukin 6; INOS: Inducible nitric oxide synthase; CASP 3: Caspase 3; α-syn: Alpha-synuclein; DNA: Deoxyribonucleic acid;ACHE: Acetyl cholinesterase; TH: Tyrosine Hydroxylase; DOPA: Dopamine. Declarations Acknowledgements I would like to sincerely thank and extend my appreciation to Ain Shams University, the Faculty of Specific Education, and the National Research Centre for their valuable support and for providing the necessary facilities to accomplish this work. Funding Declaration This study was entirely self-funded by the corresponding author and other authors and no external funding was obtained. and is intended for Open Access publication under the Springer Nature agreement with Ain Shams University. Availability of data and materials The data supporting the findings of this study are available from the corresponding author upon reasonable request. All datasets and materials used in the analysis and interpret- action of results can be shared to ensure transparency and reproducibility in line with the journal ' s data sharing policy. Competing Interests The authors declare that they have no competing interests. Author Informations Home Economics Department, Faculty of Specific Education, Ain Shams University, Cairo, Egypt Radwa A. Shaheen, Ereny W. Nagib & Usama E. Mostafa Pharmacology Department, Institute of Medical Research and Clinical Studies, National Research Centre, Giza, Egypt Mohamed M. Amin & Rehab R. Hegazy Corresponding Author RAS. She conceived and designed the study, performed the experimental work, and wrote the first draft of the manuscript. Author s MMA. He conducted some behavioral tests. EWN. Help write manuscript draft. RRH . She performed statistical analyses, contributed to data interpretation, conducted some behavioral tests, and provided technical support during the experiment. UEM. Contributed to the study design, critically reviewed the manuscript, and assisted in writing the manuscript and interpreting the results. All authors read and approved the final manuscript. Ethics approval and consent to participate The experimental protocol was reviewed and approved by the Ethics Committee of the Faculty of Specific Education, Ain Shams University. All animal procedures were conducted in accordance with the guidelines of the committee and international standards for the care and use of laboratory animals. Consent for publication : Not applicable. ORCID: https://orcid.org/0009-0005-8957-9534 References G. Naik, R.G. Shaikh, S.P. Dipankar, J.K. Thilaka, H. Sharma, D. Sharma, Neuroprotective Effects of Natural Plant Extracts (Ginkgo biloba, Curcuma longa, and Withania somnifera) in Parkinson’s Disease Models: A Meta-Analysis, Disease and Health: Research Developments, (2025) 114. DOI: https://doi.org/10.9734/bpi/dhrd/v8/4833 C. Angeloni, D. Vauzour, Natural products and neuroprotection, in, MDPI, 2019, pp. 5570. https://doi.org/10.3390/ijms20225570 D. Georgescu, O.E. Ancusa, L.A. Georgescu, I. Ionita, D. Reisz, Nonmotor gastrointestinal disorders in older patients with Parkinson’s disease: is there hope?, Clinical interventions in aging, (2016) 1601-1608. https://doi.org/10.2147/CIA.S106284 S.-C. Fu, L.-C. Shih, P.-H. Wu, Y.-C. Hsieh, C.-H. Lee, S.-H. Lin, H. Wang, Exploring the causal effect of constipation on Parkinson’s disease through mediation analysis of microbial data, Frontiers in Cellular and Infection Microbiology, 12 (2022) 871710. https://doi.org/10.3389/fcimb.2022.871710 A. Segal, Y. Zlotnik, K. Moyal-Atias, R. Abuhasira, G. Ifergane, Fecal microbiota transplant as a potential treatment for Parkinson's disease–a case series, Clinical Neurology and Neurosurgery, 207 (2021) 106791. https://doi.org/10.1016/j.clineuro.2021.106791 E. Cassani, G. Privitera, G. Pezzoli, C. Pusani, C. Madio, L. Iorio, M. Barichella, Use of probiotics for the treatment of constipation in Parkinson's disease patients, Minerva gastroenterologica e dietologica, 57 (2011) 117-121. M.N. Han, D.I. Finkelstein, R.M. McQuade, S. Diwakarla, Gastrointestinal dysfunction in Parkinson’s disease: current and potential therapeutics, Journal of personalized medicine, 12 (2022) 144. https://doi.org/10.3390/jpm12020144 M.U. Rehman, A.F. Wali, A. Ahmad, S. Shakeel, S. Rasool, R. Ali, S.M. Rashid, H. Madkhali, M.A. Ganaie, R. Khan, Neuroprotective strategies for neurological disorders by natural products: an update, Current neuropharmacology, 17 (2019) 247-267. DOI: https://doi.org/10.2174/1570159X16666180911124605 B. Chen, J. Zhao, R. Zhang, L. Zhang, Q. Zhang, H. Yang, J. An, Neuroprotective effects of natural compounds on neurotoxin-induced oxidative stress and cell apoptosis, Nutritional neuroscience, 25 (2022) 1078-1099. https://doi.org/10.1080/1028415X.2020.1840035 V.S. Nade, L.A. Kawale, S.S. Zambre, A.B. Kapure, Neuroprotective potential of Beta vulgaris L. in Parkinson's disease, Indian journal of pharmacology, 47 (2015) 403-408. DOI: 10.4103/0253-7613.161263 E. Hadipour, A. Taleghani, N. Tayarani‐Najaran, Z. Tayarani‐Najaran, Biological effects of red beetroot and betalains: A review, Phytotherapy research, 34 (2020) 1847-1867. https://doi.org/10.1002/ptr.6653 O. Giampaoli, C. Ieno, F. Sciubba, M. Spagnoli, A. Miccheli, A. Tomassini, W. Aureli, L. Fattorini, Metabolic biomarkers of red beetroot juice intake at rest and after physical exercise, Nutrients, 15 (2023) 2026. https://doi.org/10.3390/nu15092026 R. Sunnadeniya, A. Bean, M. Brown, N. Akhavan, G. Hatlestad, A. Gonzalez, V.V. Symonds, A. Lloyd, Tyrosine hydroxylation in betalain pigment biosynthesis is performed by cytochrome P450 enzymes in beets (Beta vulgaris), PloS one, 11 (2016) e0149417. https://doi.org/10.1371/journal.pone.0149417 P. Hemarajata, J. Versalovic, Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation, Therapeutic advances in gastroenterology, 6 (2013) 39-51. https://doi.org/10.1177/1756283X12459294 J. Wang, Q. Liang, Q. Zhao, Q. Tang, A.F. Ahmed, Y. Zhang, W. Kang, The effect of microbial composition and proteomic on improvement of functional constipation by Chrysanthemum morifolium polysaccharide, Food and Chemical Toxicology, 153 (2021) 112305. https://doi.org/10.1016/j.fct.2021.112305 H.-J. Wu, E. Wu, The role of gut microbiota in immune homeostasis and autoimmunity, Gut microbes, 3 (2012) 4-14. https://doi.org/10.4161/gmic.19320 Y. Belkaid, T.W. Hand, Role of the microbiota in immunity and inflammation, Cell, 157 (2014) 121-141. http://dx.doi.org/10.1016/j.cell.2014.03.011 N.F. Abdelkader, H.A. Farid, E.R. Youness, O.M. Abdel-Salam, H.F. Zaki, The role of KATP channel blockade and activation in the protection against neurodegeneration in the rotenone model of Parkinson's disease, Life Sciences, 257 (2020) 118070. https://doi.org/10.1016/j.lfs.2020.118070 H.R.A. Salem, A. El-Raouf, E.M. Saleh, K. Shalaby, Influence of hesperidin combined with Sinemet on genetical and biochemical abnormalities in rats suffering from Parkinson’s disease, Life Sci J, 9 (2012) 930-945. G. Albasher, T. Albrahim, N. Alsultan, S. Alfaraj, M.S. Alharthi, R.B. Kassab, A.E. Abdel Moneim, Red beetroot extract mitigates chlorpyrifos-induced reprotoxicity associated with oxidative stress, inflammation, and apoptosis in rats, Environmental Science and Pollution Research, 27 (2020) 3979-3991. https://doi.org/10.1007/s11356-019-07009-6 T. Li, Q. Yan, Y. Wen, J. Liu, J. Sun, Z. Jiang, Synbiotic yogurt containing konjac mannan oligosaccharides and Bifidobacterium animalis ssp. lactis BB12 alleviates constipation in mice by modulating the stem cell factor (SCF)/c-Kit pathway and gut microbiota, Journal of Dairy Science, 104 (2021) 5239-5255. https://doi.org/10.3168/jds.2020-19449 R. Siracusa, M. Scuto, R. Fusco, A. Trovato, M.L. Ontario, R. Crea, R. Di Paola, S. Cuzzocrea, V. Calabrese, Anti-inflammatory and anti-oxidant activity of Hidrox® in rotenone-induced Parkinson’s disease in mice, Antioxidants, 9 (2020) 824. https://doi.org/10.3390/antiox9090824 J.B. Carroll, A.L. Southwell, R.K. Graham, J.P. Lerch, D.E. Ehrnhoefer, L.-P. Cao, W.-N. Zhang, Y. Deng, N. Bissada, R.M. Henkelman, Mice lacking caspase-2 are protected from behavioral changes, but not pathology, in the YAC128 model of Huntington disease, Molecular neurodegeneration, 6 (2011) 59. M. Wada, M.J. Ang, P.D. Weerasinghe-Mudiyanselage, S.-H. Kim, J.-C. Kim, T. Shin, C. Moon, Behavioral characterization in MPTP/p mouse model of Parkinson’s disease, Journal of Integrative Neuroscience, 20 (2021) 307-320. https://doi.org/10.31083/j.jin2002030 L.Y. Chen, S.H. Tai, Y.C. Hung, S.Y. Huang, Z.C. Kuo, A.H. Lee, H.H. Hsu, T.S. Wu, E.J. Lee, Anti‐oxidative and anti‐inflammatory effects of Ginkgo biloba extract (EGb761) on hindlimb skeletal muscle ischemia–reperfusion injury in rats, Physiological reports, 12 (2024) e16050. https://doi.org/10.14814/phy2.16050 J. Liu, X. Lv, T. Ye, M. Zhao, Z. Chen, Y. Zhang, W. Yang, H. Xie, L. Zhan, L. Chen, Microbiota-microglia crosstalk between Blautia producta and neuroinflammation of Parkinson's disease: A bench-to-bedside translational approach, Brain, Behavior, and Immunity, 117 (2024) 270-282. https://doi.org/10.1016/j.bbi.2024.01.010 M. Kujawska, M. Jourdes, Ł. Witucki, M. Karaźniewicz-Łada, M. Szulc, A. Górska, P.Ł. Mikołajczak, P.-L. Teissedre, J. Jodynis-Liebert, Pomegranate juice ameliorates dopamine release and behavioral deficits in a rat model of Parkinson’s disease, Brain Sciences, 11 (2021) 1127. https://doi.org/10.3390/brainsci11091127 A.D. Nadeev, K.A. Kritskaya, E.I. Fedotova, A.V. Berezhnov, «One Small Step for Mouse»: High CO2 Inhalation as a New Therapeutic Strategy for Parkinson’s Disease, Biomedicines, 10 (2022) 2832. https://doi.org/10.3390/biomedicines10112832 M.E. Crupi R, Marino A, La Spada G, Bramanti P, Cuzzocrea, S.E. S, Melatonin treatment mimics the antidepressant action in chronic corticosterone-treated mice., J Pineal Res(2): ((2010)) 123–129.49 https://doi.org/10.1111/j.1600-079X.2010.00775.x S.J.R. Ali, P.S. (2016). Effect of monocrotophos, an organophosphorus insecticide, on the striatal dopaminergic system in a mouse model of Parkinson’s disease. Toxicology and Industrial Health 32(7): 1153-1165. doi. org/10.1177/0748233714547733. P.R. Sanberg, Bunsey, M. D., Giordano, M., & Norman, A. B. (1988). The catalepsy test: its ups and downs. Behavioral neuroscience, 102(5), 748.‏. F. Khakpai, Ebrahimi-Ghiri, M., Alijanpour, S., & Zarrindast, M.R .(2019). Ketamine-induced antidepressant like effects in mice: a possible involvement of cannabinoid system. Biomed Pharmacother 112:108717. https://doi.org/10.1016/j.biopha.2019.108717 M. Dolatshahi, Farbood, Y., Sarkaki, A., Mansouri, S. M. T., & Khodadadi, A. (2015). Ellagic acid improves hyperalgesia and cognitive deficiency in 6-hydroxidopamine induced rat model of Parkinson’s disease. Iranian journal of basic medical sciences, 18(1), 38.‏ F. Faivre, Sánchez-Catalán, M. J., Dovero, S., Bido, S., Joshi, A., Bezard, E., & Barrot, M. (2020). Ablation of the tail of the ventral tegmental area compensates symptoms in an experimental model of Parkinson's disease. Neurobiology of Disease, 139, 104818.‏ https://doi.org/10.1016/j.nbd.2020.104818 J. Wu, Cheng, Yan, Zhang, Rong, Liu, Dong, Luo, Yu-Mei, Chen, Kun-Lun, Ren., & Song-Zhang. (2017). P2Y1R is involved in visceral hypersensitivity in rats with experimental irritable bowel syndrome. World J. Gastroenterol. 23 (34), 6339 https://doi.org/10.3748/wjg.v23.i34.6339. O.J.M.c.u.r.s.T. Dunn. (1964). Multiple Comparisons Using Rank Sums. Technometrics , 6 (3), 241–252. https://doi.org/10.1080/00401706.1964.10490181 Y.H. Leem, Park, J. S., Park, J. E., Kim, D. Y., & Kim, H. S. (2022). Neurogenic effects of rotarod walking exercise in subventricular zone, subgranular zone, and substantia nigra in MPTP-induced Parkinson’s disease mice. Scientific reports, 12(1), 10544.‏ https://doi.org/10.1038/s41598-022-14823-5 H.M. Shan, Maurer, M. A., & Schwab, M. E. (2023). Four-parameter analysis in modified Rotarod test for detecting minor motor deficits in mice. BMC biology, 21(1), 177. https://doi.org/10.1186/s12915-023-01679-y T. Hortobágyi, Vetrovsky, T., Uematsu, A., Sanders, L., da Silva Costa, A. A., Batistela, R. A., & Tollár, J. (2023). Beam walking as a new measure of dynamic balance to predict falls. DOI: https://doi.org/10.21203/rs.3.rs-3268679/v1 A.D. Björklund, S. B. (2019). The amphetamine induced rotation test: a re-assessment of its use as a tool to monitor motor impairment and functional recovery in rodent models of Parkinson’s disease. Journal of Parkinson’s Disease, 9(1), 17-29.‏. https://doi.org/10.3233/JPD-181525 Filipiuc, (2024). JWH-182: a safe and effective synthetic c*nnabinoid for chemotherapy-induced neuropathic pain in preclinical models, Scientific reports . https://doi.org/10.1038/s41598-024-67154-y M. Khorasani, Kiasalari, Z., Ghasemi, R., Fakour, M., Keshtkar, S., & Roghani, M. (2020). The effect of nobiletin on performance of rats in forced swimming and elevated plus maze tests in intranigral lipopolysaccharide rat model of Parkinson's disease. Journal of Basic and Clinical Pathophysiology, 8(1), 28-34.‏ DOI 10.22070/JBCP.2020.4355.1115 M. Ebrahimi-Ghiri, Shahini, F., & Zarrindast, M. R. (2021). The effect of URB597, exercise or their combination on the performance of 6-OHDA mouse model of Parkinson disease in the elevated plus maze, tail suspension test and step-down task. Metabolic Brain Disease, 36(8), 2579-2588.‏ K.R. Luciani, Frie, J. A., & Khokhar, J. Y. (2020). An open source automated bar test for measuring catalepsy in rats. Eneuro, 7 (3). doi.org/10.1523/ENEURO.0488-19.2020 G.C.D. Nascimento, Bariotto-Dos-Santos, K., Leite-Panissi, C. R. A., Del-Bel, E. A., & Bortolanza, M. (2018). Nociceptive response to L-DOPA-induced dyskinesia in hemiparkinsonian rats. Neurotoxicity Research, 34, 799-807.‏ https://doi.org/10.1007/s12640-018-9896-0 A.B. Tryc, Goldbecker, A., Berding, G., Rümke, S., Afshar, K., Shahrezaei, G. H., & Weissenborn, K. (2013). Cirrhosis-related Parkinsonism: prevalence, mechanisms and response to treatments. Journal of Hepatology, 58(4), 698-705.‏ https://doi.org/10.1016/j.jhep.2012.11.043 J.S. Bajaj, Gentili, A., Wade, J. B., & Godschalk, M. (2022). Specific challenges in geriatric cirrhosis and hepatic encephalopathy. Clinical Gastroenterology and Hepatology, 20(8), S20-S29.‏ https://doi.org/10.1016/j.cgh.2022.04.035 Y.S. Kim, A.S Lee, H.J. Hur, S.H. Lee, H.J.Na, & M.J. Sung, (2023). Renoprotective effect of Chrysanthemum coronarium L. extract on adenine-induced chronic kidney disease in mice. Pharmaceuticals, 16(7), 1048. ‏ https://doi.org/10.3390/ph16071048 X. Dong-Chen, Yong, C., Yang, X., Chen-Yu, S., & Li-Hua, P. (2023). "Signaling pathways in Parkinson's disease: molecular mechanisms and therapeutic interventions". Signal Transduction and Targeted Therapy. 8 (1): 1–18. doi:10.1038/s41392-023-01353-3. ISSN 2059-3635. PMC 9944326. PMID 36810524. https://doi.org/10.1038/s41392-023-01353-3 S. Latif, Jahangeer, M., Razia, D. M., Ashiq, M., Ghaffar, A., Akram, M., & Ansari, M. A. (2021). Dopamine in Parkinson's disease. Clinica chimica acta, 522, 114-126. https://doi.org/10.1016/j.cca.2021.08.009 H. Wang, C. Zhang, M. Li, C. Liu, J. Wang, X. Ou, Y. Han, Antimicrobial peptides mediate apoptosis by changing mitochondrial membrane permeability, International Journal of Molecular Sciences, 23 (2022) 12732. https://doi.org/10.3390/ijms232112732 A. Rauf, H. Badoni, T. Abu-Izneid, A. Olatunde, M.M. Rahman, S. Painuli, P. Semwal, P. Wilairatana, M.S. Mubarak, Neuroinflammatory markers: key indicators in the pathology of neurodegenerative diseases, Molecules, 27 (2022) 3194. https://doi.org/10.3390/molecules27103194 M. Mahran, M. Elkabary, H. Saad, Potential Laxative Effects of Dried Plums (Prunes) and Red Beetroot on Loperamide-Induced Constipation in Adult Rats, Journal of Home Economics-Menofia University, 34 (2024) 175-203.DOI 10.21608/MKAS.2024.291926.1316 H. Doi, R. Sakakibara, M. Sato, T. Masaka, M. Kishi, A. Tateno, F. Tateno, Y. Tsuyusaki, O. Takahashi, Plasma levodopa peak delay and impaired gastric emptying in Parkinson's disease, Journal of the neurological sciences, 319 (2012) 86-88. https://doi.org/10.1016/j.jns.2012.05.010 X.-S. Zeng, W.-S. Geng, J.-J. Jia, Neurotoxin-induced animal models of Parkinson disease: pathogenic mechanism and assessment, ASN neuro, 10 (2018) 1759091418777438. J.D. Guo, X. Zhao, Y. Li, G.R. Li, X.L. Liu, Damage to dopaminergic neurons by oxidative stress in Parkinson's disease, International journal of molecular medicine, 41 (2018) 1817-1825. https://doi.org/10.3892/ijmm.2018.3406 M. Makav, H.A. Eroğlu, Recuperative effect of estrogen on rotenone-induced experimental model of Parkinson’s disease in rats, Environmental Science and Pollution Research, 28 (2021) 21266-21275. https://doi.org/10.1007/s11356-020-11985-5 P. Perez-Pardo, L.M. Broersen, T. Kliest, N. Van Wijk, A. Attali, J. Garssen, A.D. Kraneveld, Additive effects of levodopa and a neurorestorative diet in a mouse model of Parkinson’s disease, Frontiers in Aging Neuroscience, 10 (2018) 237. https://doi.org/10.3389/fnagi.2018.00237 T. Leroy, R.J. Baggen, N. Lefeber, N. Herssens, P. Santens, M. De Letter, L. Maes, K. Bouche, A. Van Bladel, Effects of oral levodopa on balance in people with idiopathic Parkinson’s disease, Journal of Parkinson’s Disease, 13 (2023) 3-23. https://doi.org/10.3233/JPD-223536 N. Kwankaew, H. Okuda, A. Aye‐Mon, T. Ishikawa, K. Hori, P. Sonthi, Y. Kozakai, N. Ozaki, Antihypersensitivity effect of betanin (red beetroot extract) via modulation of microglial activation in a mouse model of neuropathic pain, European Journal of Pain, 25 (2021) 1788-1803. https://doi.org/10.1002/ejp.1790 Z. Zhao, J. Ning, X.-q. Bao, M. Shang, J. Ma, G. Li, D. Zhang, Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis, Microbiome, 9 (2021) 226. https://doi.org/10.1186/s40168-021-01107-9 B. Avcı, C. Günaydın, T. Güvenç, C.K. Yavuz, N. Kuruca, S.S. Bilge, Idebenone ameliorates rotenone-induced Parkinson’s disease in rats through decreasing lipid peroxidation, Neurochemical Research, 46 (2021) 513-522. https://doi.org/10.1007/s11064-020-03186-w S. Gellhaar, D. Marcellino, M. Abrams, D. Galter, Chronic L‐DOPA induces hyperactivity, normalization of gait and dyskinetic behavior in MitoPark mice, Genes, Brain and Behavior, 14 (2015) 260-270. https://doi.org/10.1111/gbb.12210 M.H. ElSayed, H.M. Atif, M.A. Eladl, S.M. Elaidy, A.M. Helaly, F.A. Hisham, N.E. Farag, N.M. Osman, A.T. Ibrahiem, H.W. Khella, Betanin improves motor function and alleviates experimental Parkinsonism via downregulation of TLR4/MyD88/NF-κB pathway: Molecular docking and biological investigations, Biomedicine & Pharmacotherapy, 164 (2023) 114917. https://doi.org/10.1016/j.biopha.2023.114917 J. Kim, B.-E. Yoon, Y.K. Jeon, Effect of treadmill exercise and probiotic ingestion on motor coordination and brain activity in adolescent mice, in: Healthcare, MDPI, 2020, pp. 7. https://doi.org/10.3390/healthcare9010007 C. Pont‐Sunyer, A. Hotter, C. Gaig, K. Seppi, Y. Compta, R. Katzenschlager, N. Mas, D. Hofeneder, T. Brücke, A. Bayés, The O nset of N onmotor S ymptoms in P arkinson's disease (T he ONSET PD S tudy), Movement Disorders, 30 (2015) 229-237. https://doi.org/10.1002/mds.26077 H. Chen, E.A. Burton, G.W. Ross, X. Huang, R. Savica, R.D. Abbott, A. Ascherio, J.N. Caviness, X. Gao, K.A. Gray, Research on the premotor symptoms of Parkinson’s disease: clinical and etiological implications, Environmental health perspectives, 121 (2013) 1245-1252. https://doi.org/10.1289/ehp.1306967 O.G. Ahmed, M. Mahmoud, A.A. Abdelhamid, Behavioral Evaluation of rotenone model of Parkinson’s disease in male Wistar rats, Sohag Medical Journal, 24 . (2020) 8-14. DOI: 10.21608/smj.2020.21596.1089 P.M. Luthra, S.K. Barodia, R. Raghubir, Antagonism of haloperidol-induced swim impairment in L-dopa and caffeine treated mice: a pre-clinical model to study Parkinson's disease, Journal of neuroscience methods, 178 (2009) 284-290. https://doi.org/10.1016/j.jneumeth.2008.12.019 K. Sulakhiya, V.K. Patel, R. Saxena, J. Dashore, A.K. Srivastava, M. Rathore, Effect of Beta vulgaris Linn. leaves extract on anxiety-and depressive-like behavior and oxidative stress in mice after acute restraint stress, Pharmacognosy research, 8 (2016) 1. doi: 10.4103/0974-8490.171100 Q.F. Liu, H.-M. Kim, S. Lim, M.-J. Chung, C.-Y. Lim, B.-S. Koo, S.-S. Kang, Effect of probiotic administration on gut microbiota and depressive behaviors in mice, DARU Journal of Pharmaceutical Sciences, 28 (2020) 181-189. https://doi.org/10.1007/s40199-020-00329-w S. Li, Y. Zhua, X. Liu, Parkinsonism in liver diseases or dysfunction, Medicina Clínica, 163 (2024) 461-468. https://doi.org/10.1016/j.medcli.2024.04.022 H. Wang, M. Huo, Y. Jin, Y. Wang, X. Wang, W. Yu, X. Jiang, Rotenone induces hepatotoxicity in rats by activating the mitochondrial pathway of apoptosis, Toxicology Mechanisms and Methods, 32 (2022) 510-517. https://doi.org/10.1080/15376516.2022.2049940 A.U. Kura, B. Saifullah, P.-S. Cheah, M.Z. Hussein, N. Azmi, S. Fakurazi, Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite, Nanoscale Research Letters, 10 (2015) 105. DOI 10.1186/s11671-015-0742-5 E.A. Gashash, H. Wahba, The efficiency of red grapes and beetroot juice as nutrients for improving blood glucose levels, renal function, liver enzymes, and immunity factors, مجلة دراسات وبحوث التربية النوعية , 11 (2025) 138-154. DOI: 10.21608/JSEZU.2025.402707 S. Hasan, M.A.I. Amin, M. Mia, S. Khatun, Y. Arafat, M.R. Gofur, M.M. Islam, M.E. Hosen, K.S. Almaary, G. Fentahun Wondmie, Yogurt Supplementation Can Ameliorate Fatty Liver Diseases and Metabolic Syndrome in High Fat‐Induced Conditions in Mice, Food Science & Nutrition, 13 (2025) e4650. https://doi.org/10.1002/fsn3.4650 M.R. Shahein, E.S.H. Atwaa, H.A. Radwan, A.A. Elmeligy, A.A. Hafiz, A. Albrakati, E.K. Elmahallawy, Production of a yogurt drink enriched with Golden berry (Physalis pubescens L.) juice and its therapeutic effect on hepatitis in rats, Fermentation, 8 (2022) 112. https://doi.org/10.3390/fermentation8030112 G.O. Udeani, G.-M. Zhao, Y.G. Shin, J.W. Kosmeder Ii, C.W. Beecher, A.D. Kinghorn, R.M. Moriarty, R.C. Moon, J.M. Pezzuto, Pharmacokinetics of deguelin, a cancer chemopreventive agent in rats, Cancer chemotherapy and pharmacology, 47 (2001) 263-268.DOI 10.1007/s002800000187 J. Jain, W. Hasan, P. Biswas, R.S. Yadav, D. Jat, International Journal of Human Anatomy. L. Cheng, P. Yao, H. Wang, Q. Yuan, X. Wang, W. Feng, F. Sun, Q. Wang, Effects of Lactobacillus plantarum HFY15 on lupus nephritis in mice by regulation of the TGF-β1 signaling pathway, Drug Design, Development and Therapy, (2022) 2851-2860. https://doi.org/10.2147/DDDT.S363974 B.L. Santos-Lobato, Towards a methodological uniformization of environmental risk studies in Parkinson’s disease, npj Parkinson's Disease, 10 (2024) 86. O.M. Abdel-Salam, M.E.-S. El-Shamarka, N. Shaffie, Neuroprotective effect of capsaicin against rotenone-induced Parkinson’s disease in mice, International Journal of Halal Research, 6 (2024) 1-11. DOI : https://doi.org/10.18517/ijhr.6.1.1-14.2024 M. Ayaz, F. Anwar, U. Saleem, I. Shahzadi, B. Ahmad, A. Mir, T. Ismail, Parkinsonism attenuation by antihistamines via downregulating the oxidative stress, histamine, and inflammation, ACS omega, 7 (2022) 14772-14783. https://doi.org/10.1021/acsomega.2c00145 ACS A.P. Sushama, Onkar, A. A., Shripad, N. S., & Jyoti, P. J. (2013). Biological sources of L-DOPA: An alternative approach. *Advances in Parkinson's Disease, 2*(3), 81–87. https://doi.org/10.4236/apd.2013.23016 W. Thong-Asa, S. Jedsadavitayakol, S. Jutarattananon, Benefits of betanin in rotenone-induced Parkinson mice, Metabolic brain disease, 36 (2021) 2567-2577.https://doi.org/10.1007/s11011-021-00826-0 O.M. Abdel-Salam, S.M.Y. Morsy, E.R. Youness, N.N. Yassen, A.A. Sleem, The effect of low dose amphetamine in rotenone-induced toxicity in a mice model of Parkinson’s disease, Iranian Journal of Basic Medical Sciences, 23 (2020) 1207. doi: 10.22038/ijbms.2020.45175.10524 R. Landau, R. Halperin, P. Sullivan, Z. Zibly, A. Leibowitz, D.S. Goldstein, Y. Sharabi, The rat rotenone model reproduces the abnormal pattern of central catecholamine metabolism found in Parkinson's disease, Disease Models & Mechanisms, 15 (2022) dmm049082. https://doi.org/10.1242/dmm.049082 W. Hasan, R.K. Kori, J. Jain, R.S. Yadav, D. Jat, Neuroprotective effects of mitochondria‐targeted curcumin against rotenone‐induced oxidative damage in cerebellum of mice, Journal of biochemical and molecular toxicology, 34 (2020) e22416. https://doi.org/10.1002/jbt.22416 X. Chen, Z. Wang, W. Yang, Y. Fu, Levodopa improves behavioral deficits of mice with Parkinson's disease symptoms via curbing NLRP3 inflammasome activation and enhancing tyrosine hydroxylase levels in the striatum and substantia nigra, Journal of integrative neuroscience, 23 (2024) 2. https://doi.org/10.31083/j.jin2301002 P. Ghanbari, S. Khajehzadeh, A. Sayyed, D. Raeisi, O. Salehi, The effect of high intensity interval training with beetroot (Beta vulgaris) juice supplementation on serotonin and dopamine receptors expression, anxiety and depression in middle-aged diabetic rats, Avicenna Journal of Phytomedicine, 12 (2022) 627. doi: 10.22038/AJP.2022.20895 T.A. Olasehinde, S.I. Oyeleye, C.U. Ibeji, G. Oboh, Beetroot supplemented diet exhibit anti-amnesic effect via modulation of cholinesterases, purinergic enzymes, monoamine oxidase and attenuation of redox imbalance in the brain of scopolamine treated male rats, Nutritional Neuroscience, 25 (2022) 1011-1025. https://doi.org/10.1080/1028415X.2020.1831260 T.-H. Hsieh, C.-W. Kuo, K.-H. Hsieh, M.-J. Shieh, C.-W. Peng, Y.-C. Chen, Y.-L. Chang, Y.-Z. Huang, C.-C. Chen, P.-K. Chang, Probiotics alleviate the progressive deterioration of motor functions in a mouse model of Parkinson’s disease, Brain sciences, 10 (2020) 206. https://doi.org/10.3390/brainsci10040206 R. Balakrishnan, D. Vijayraja, T. Mohankumar, D. Manimaran, P. Ganesan, D.-K. Choi, N. Elangovan, Isolongifolene mitigates rotenone-induced dopamine depletion and motor deficits through anti-oxidative and anti-apoptotic effects in a rat model of Parkinson's disease, Journal of chemical neuroanatomy, 112 (2021) 101890. https://doi.org/10.1016/j.jchemneu.2020.101890 W.K. Khalil, N. Assaf, S.A. ElShebiney, N.A. Salem, Neuroprotective effects of bee venom acupuncture therapy against rotenone-induced oxidative stress and apoptosis, Neurochemistry international, 80 (2015) 79-86. https://doi.org/10.1016/j.neuint.2014.11.008 T.K. Motawi, N.A. Sadik, M.A. Hamed, S.A. Ali, W.K. Khalil, Y.R. Ahmed, Potential therapeutic effects of antagonizing adenosine A2A receptor, curcumin and niacin in rotenone-induced Parkinson’s disease mice model, Molecular and cellular biochemistry, 465 (2020) 89-102. Molecular and Cellular https://doi.org/10.1007/s11010-019-03670-0 B.C. Phukan, R. Roy, R. Paul, M.K. Mazumder, J. Nath, P. Bhattacharya, A. Borah, Traversing through the cell signaling pathways of neuroprotection by betanin: Therapeutic relevance to Alzheimer’s Disease and Parkinson’s Disease, Metabolic Brain Disease, 38 (2023) 805-817. L. Wang, Z. Zhao, L. Zhao, Y. Zhao, G. Yang, C. Wang, L. Gao, C. Niu, S. Li, Lactobacillus plantarum DP189 reduces α-SYN aggravation in MPTP-induced Parkinson’s disease mice via regulating oxidative damage, inflammation, and gut microbiota disorder, Journal of agricultural and food chemistry, 70 (2022) 1163-1173. https://doi.org/10.1021/acs.jafc.1c07711 N. Zhang, D. Dou, X. Ran, T. Kang, Neuroprotective effect of arctigenin against neuroinflammation and oxidative stress induced by rotenone, Rsc Advances, 8 (2018) 2280-2292. DOI: 10.1039/C7RA10906G E. Abdel-Sattar, E.A. Mahrous, M.M. Thabet, D.M.Y. Elnaggar, A.M. Youssef, R. Elhawary, S.A. Zaitone, C. Rodríguez-Pérez, A. Segura-Carretero, R.H. Mekky, Methanolic extracts of a selected Egyptian Vicia faba cultivar mitigate the oxidative/inflammatory burden and afford neuroprotection in a mouse model of Parkinson’s disease, Inflammopharmacology, 29 (2021) 221-235. nfammopharmacology ( https://doi.org/10.1007/s10787-020-00768-6 S.A. Khan, M.N. Alsulami, A.A. Alsehimi, M.S. Alzahrani, D.A. Mosule, H.H. Albohiri, Beta vulgaris Betalains Mitigate Parasitemia and Brain Oxidative Stress Induced by Plasmodium berghei in Mice, Pharmaceuticals, 17 (2024) 1064. doi: 10.3390/ph17081064 Y. Ano, M. Ozawa, T. Kutsukake, S. Sugiyama, K. Uchida, A. Yoshida, H. Nakayama, Preventive effects of a fermented dairy product against Alzheimer’s disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity, PloS one, 10 (2015) e0118512. https://doi.org/10.1371/journal.pone.0118512 J. Gao, Identifying Probiotics that Modulate Mitophagy in Models of Mitochondrial Dysfunction, in, University of Toronto (Canada), 2023. C. Pellegrini, L. Antonioli, R. Colucci, E. Tirotta, D. Gentile, C. Ippolito, C. Segnani, G. Levandis, S. Cerri, F. Blandini, Effects of L-DOPA/benserazide co-treatment on colonic excitatory cholinergic motility and enteric inflammation following dopaminergic nigrostriatal neurodegeneration, Neuropharmacology, 123 (2017) 22-33. https://doi.org/10.1016/j.neuropharm.2017.05.016 G.-P. Ko, H. Jo, J. Kim, J.S. Kim, K.-H. Boo, C.S. Kim, Enterotype-Specific Effects of Red Beetroot (Beta vulgaris L.) Powder and Betanin on Human Gut Microbiota: A Preliminary Study Based on In Vitro Fecal Fermentation Model, Life, 14 (2024) 1391. doi: 10.3390/life14111391 L.R. Perazza, N. Daniel, M.-J. Dubois, G. Pilon, T.V. Varin, M. Blais, J.L.M. Gonzales, M. Bouchard, C. Asselin, M. Lessard, Distinct effects of milk-derived and fermented dairy protein on gut microbiota and cardiometabolic markers in diet-induced obese mice, The Journal of Nutrition, 150 (2020) 2673-2686. https://doi.org/10.1093/jn/nxaa217 C. Chu, L. Yu, Y. Li, H. Guo, Q. Zhai, W. Chen, F. Tian, Lactobacillus plantarum CCFM405 against rotenone-induced Parkinson’s disease mice via regulating gut microbiota and branched-chain amino acids biosynthesis, Nutrients, 15 (2023) 1737. https://doi.org/10.3390/nu15071737 N. Radisavljevic, A. Metcalfe-Roach, M. Cirstea, M.M. Tabusi, T. Bozorgmehr, H. Bar-Yoseph, B.B. Finlay, Microbiota-mediated effects of Parkinson’s disease medications on Parkinsonian non-motor symptoms in male transgenic mice, Msphere, 9 (2024) e00379-00323. https://doi.org/10.1128/msphere.00379-23 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7602198","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":518716439,"identity":"0ad37f1e-5226-413f-a2b4-d6d4f53af247","order_by":0,"name":"Radwa A. Shaheen","email":"data:image/png;base64,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","orcid":"","institution":"Ain Shams University","correspondingAuthor":true,"prefix":"","firstName":"Radwa","middleName":"A.","lastName":"Shaheen","suffix":""},{"id":518716440,"identity":"fff24f86-521e-4664-97ea-02ad9ca27820","order_by":1,"name":"Mohamed M. Amin","email":"","orcid":"","institution":"National Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"M.","lastName":"Amin","suffix":""},{"id":518716441,"identity":"420748b6-68d9-401e-905c-825d9c47a71d","order_by":2,"name":"Ereny W. Nagib","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Ereny","middleName":"W.","lastName":"Nagib","suffix":""},{"id":518716442,"identity":"f219087b-fae2-42f7-965a-402003ceccce","order_by":3,"name":"Rehab R. Hegazy","email":"","orcid":"","institution":"National Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Rehab","middleName":"R.","lastName":"Hegazy","suffix":""},{"id":518716443,"identity":"70875e58-a610-4f1e-86f2-bf06b59a3c06","order_by":4,"name":"Usama E. Mostafa","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Usama","middleName":"E.","lastName":"Mostafa","suffix":""}],"badges":[],"createdAt":"2025-09-12 16:08:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7602198/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7602198/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":92067530,"identity":"9fd5f663-87a8-454a-a98b-3643e6be4b9d","added_by":"auto","created_at":"2025-09-24 09:11:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":50157,"visible":true,"origin":"","legend":"\u003cp\u003eThe effect of beetroot - fortified yogurt as a natural source of levodopa compared to drug therapy in male mice suffering from parkinson's disease on the running time (A) and number of Falls (B) on rotarod test ; balance beam test (D) ; Each bar with vertical line represents mean ± SD of 6 mice per group. Similar superscript mean insignificant difference, while different letters mean significant difference between groups at \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7602198/v1/0af70ea14b562539de8241cc.png"},{"id":92067421,"identity":"69846293-59ae-49d3-930b-7f9474fc5ce9","added_by":"auto","created_at":"2025-09-24 09:11:27","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":50611,"visible":true,"origin":"","legend":"\u003cp\u003eThe effect of beetroot - fortified yogurt as a natural source of levodopa compared to drug therapy on cylinder test(A) and activity cage test (B) in male mice suffering from Parkinson's disease. Each bar with vertical line represents mean ± SD of 6 mice per group. Similar superscript mean insignificant difference, while different letters mean significant difference between groups at \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7602198/v1/c6fef614594c411509e1bc47.png"},{"id":92067500,"identity":"32b59490-e0d1-440d-9da6-88172b149857","added_by":"auto","created_at":"2025-09-24 09:11:37","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":80949,"visible":true,"origin":"","legend":"\u003cp\u003eThe effect of beetroot - fortified yogurt as a natural source of levodopa compared to drug therapy on forced swim test (A); tail suspension test (B); catalepsy test (C) and Hot Plate test (D) in male mice suffering from parkinson's disease. Each bar with vertical line represents mean ± SD of 6 mice per group. Similar superscript mean insignificant difference, while different letters mean significant difference between groups at \u003cem\u003ep\u003c/em\u003e\u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7602198/v1/aaf7cac7feaf3218adfcc550.png"},{"id":92067533,"identity":"d2e55923-b6f8-475c-9408-b2d100261737","added_by":"auto","created_at":"2025-09-24 09:11:45","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":39068,"visible":true,"origin":"","legend":"\u003cp\u003eThe effect of beetroot - fortified yogurt as a natural source of levodopa compared to drug therapy on\u003cstrong\u003e \u003c/strong\u003eALT (A) and AST (B) \u0026nbsp;in male mice suffering from parkinson's disease.Each bar with vertical line represents mean ± SD of 6 mice per group.Similar superscript mean insignificant difference, while different letters mean significant difference between groups at \u0026nbsp;\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7602198/v1/ef29fd12b40c67023428f12b.png"},{"id":92067443,"identity":"1498121c-904a-4adf-b074-a80cf3d0b5c5","added_by":"auto","created_at":"2025-09-24 09:11:33","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":52862,"visible":true,"origin":"","legend":"\u003cp\u003eThe effect of beetroot - fortified yogurt as a natural source of levodopa compared to drug therapy on urea nitrogen (A); creatinine (B) and uric acid (c) in male mice suffering from parkinson's disease. Each bar with vertical line represents mean ± SD of 6 mice per group. Similar superscript mean insignificant difference, while different letters mean significant difference between groups at \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7602198/v1/1c1ac088e378dc5cb315854e.png"},{"id":92067436,"identity":"1080176e-d39a-4bcf-84f5-4107328b0361","added_by":"auto","created_at":"2025-09-24 09:11:29","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":48821,"visible":true,"origin":"","legend":"\u003cp\u003eThe effect of beetroot - fortified yogurt as a natural source of levodopa compared to Drug therapy on MDA (A); NO (B) and GSH (B) in male mice suffering from parkinson's disease.Each bar with vertical line represents mean ± SD of 6 mice per group. Similar superscript mean insignificant difference, while different letters mean significant difference between groups at \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-7602198/v1/50c12c7153956ab2ef6e1ca7.png"},{"id":92067418,"identity":"a0629c88-153c-4f02-95bf-4b135fe8b6f4","added_by":"auto","created_at":"2025-09-24 09:11:26","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":45114,"visible":true,"origin":"","legend":"\u003cp\u003eThe effect of beetroot - fortified yogurt as a natural source of levodopa compared to drug therapy on TH (A); DOPA (B) and ACHE (C) \u0026nbsp;in male mice suffering from parkinson's disease. Each bar with vertical line represents mean ± SD of 6 mice per group. Similar superscript mean insignificant difference, while different letters mean significant difference between groups at \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-7602198/v1/85274023ecbf275ef3cd563f.png"},{"id":92067225,"identity":"b1703288-c825-4691-b7d3-6c0f8126d6d5","added_by":"auto","created_at":"2025-09-24 09:11:18","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":49742,"visible":true,"origin":"","legend":"\u003cp\u003eThe effect of beetroot - fortified yogurt as a natural source of levodopa compared to drug therapy on DNA (A); Casp-3(B) and α-syn (C) in male mice suffering from parkinson's disease. Each bar with vertical line represents mean ± SD of 6 mice per group. Similar superscript mean insignificant difference, while different letters mean significant difference between groups at \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-7602198/v1/c54e16e138691395fff11121.png"},{"id":92067446,"identity":"f2b86c0b-8e3d-458c-9a6d-9531980fb286","added_by":"auto","created_at":"2025-09-24 09:11:34","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":47420,"visible":true,"origin":"","legend":"\u003cp\u003eThe effect of beetroot - fortified yogurt as a natural source of levodopa compared to drug therapy on TNF-α (A); IL-6 (B) and Inos (C) \u0026nbsp;in male mice suffering from parkinson's disease.Each bar with vertical line represents mean ± SD of 6 mice per group. Similar superscript mean insignificant difference, while different letters mean significant difference between groups at \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-7602198/v1/be63790ef41f851f388c8813.png"},{"id":92067510,"identity":"cb1badd8-d81e-470a-930e-7c7cb419dbb7","added_by":"auto","created_at":"2025-09-24 09:11:40","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":13783,"visible":true,"origin":"","legend":"\u003cp\u003eThe effect of beetroot - fortified yogurt as a natural source of levodopa compared to drug therapy on α-Syn \u0026nbsp;in intestines tissue male mice suffering from parkinson's disease. Each bar with vertical line represents mean ± SD of 6 mice per group. Similar superscript mean insignificant difference, while different letters mean significant difference between groups at \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"10.png","url":"https://assets-eu.researchsquare.com/files/rs-7602198/v1/871b0b1918fa39784876bdae.png"},{"id":92067598,"identity":"9a726f46-527b-4afa-a440-90451465f297","added_by":"auto","created_at":"2025-09-24 09:11:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2140618,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7602198/v1/ac801408-7ac5-4f31-8aab-9fb5c948ac32.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eBeetroot (\u003cem\u003eBeta vulgaris\u003c/em\u003e) - Fortified Yogurt as a Natural Source of Levodopa Enhances in Rotenone – induced Parkinson's Disease in Mice\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eNeurodegenerative disorders pose a major global health burden, affecting millions of people worldwide and showing a notable rise in prevalence as life expectancy increases. Among the most prevalent of these conditions are Alzheimer\u0026rsquo;s disease (AD), Parkinson\u0026rsquo;s disease (PD), amyotrophic lateral sclerosis, multiple sclerosis, and Huntington\u0026rsquo;s disease [1].Parkinson\u0026apos;s disease (PD) is a neurological disorder that worsens gradually over time, often affecting a person\u0026rsquo;s ability to move. Common symptoms are muscle rigidity, tremors, bradykinesia, and reduced motor balance [2].In recent years, the influence of intestinal microorganisms has become a growing focus of scientific investigation. An increasing number of studies have identified a link between gut microbiota\u003csub\u003e7\u003c/sub\u003e and constipation associated with PD[3, 4].As a result, conventional therapeutic approaches are increasingly being replaced by microecological strategies [5, 6]. Constipation may also hinder the absorption of anti-Parkinson\u0026rsquo;s medications, including levodopa [7]. \u003c/p\u003e\n\u003cp\u003eSince ancient times, humans have depended on natural products as a fundamental source of therapeutic agents to manage various illnesses, disorders, and physical debilities. Experimental research has shown that these natural compounds possess multiple biological activities, including antioxidant, anti-inflammatory, and anti-apoptotic effects. Findings from both in vitro and in vivo studies have further confirmed their promising role in numerous preclinical models of neurodegenerative diseases[8, 9]. \u003cspan dir=\"\"\u003eBeta vulgaris, widely recognized as beetroot, has been cited in traditional medicine for its neuroprotective potential in managing various CNS-related disorders. Reviews of the literature reveal that B. vulgaris exhibits several pharmacological properties, including antidepressant, antioxidant, anticonvulsant, cerebroprotective, and hepatoprotective effects[\u003c/span\u003e\u003cspan dir=\"\"\u003e10\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e.Betanin, the primary constituent of red beetroot, highlights the therapeutic promise of beetroot and its bioactive compounds (betalains) as potential complementary treatments for multiple health conditions \u003c/span\u003e\u003cspan dir=\"\"\u003e[\u003c/span\u003e\u003cspan dir=\"\"\u003e11\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e.Structurally, betalains share a core betalamic acid unit linked to cyclo-dopa, which originates from L-dopa metabolism \u003c/span\u003e\u003cspan dir=\"\"\u003e[\u003c/span\u003e\u003cspan dir=\"\"\u003e12\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e.\u003c/span\u003e\u003cspan dir=\"\"\u003eIn addition to, the \u003c/span\u003e\u003cspan dir=\"\"\u003estudies indicate that levodopa is naturally present in beetroot as an intermediate in the metabolic pathway for the formation of betalain pigments and has been identified using HPLC/MS analysis\u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003e[\u003c/span\u003e\u003cspan dir=\"\"\u003e13\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e. \u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eYogurt contains live bacterial cultures, referred to as probiotics, which are well known for their positive effects on gastrointestinal function. These probiotics support intestinal microbial balance by stimulating the proliferation of beneficial bacteria and suppressing the growth of harmful species [14, 15].Preserving balance within the gut microbiota has been linked to better digestive function, increased nutrient uptake, and enhanced immune system efficiency [16, 17].\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.1 Animals\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003eAdult male Swiss albino mice (25 ± 5 g) were used in this study, obtained from the National Research Centre (Giza, Egypt). They were housed in plastic cages under controlled conditions (23–25 °C, 40–60% humidity, 12-h light/dark cycle) with free access to food and water.\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.2 Drugs and Chemicals\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eRotenone and the vehicle (dimethyl sulfoxide; DMSO) were purchased from Sigma-Aldrich (St Louis, MO, USA).\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eLevodopa- karpidopa (Sinemet drug) obtained from the Glopal Napi Pharmaceuticals company, Cairo, Egyp\u003c/span\u003e\u003cspan dir=\"\"\u003et.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.3 Food Items\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBeetroot and yogurt were obtained from a local market in Cairo, Egypt.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4 Experimental Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnimals were randomly allocated into 5 groups (n = 7).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGroup1. \u003c/strong\u003eRecieved the vehicle (DMSO1ml / mice, s.c 3 times / week for consecutive 3 weeks) and served as the negative control group.\u003c/p\u003e\n\u003cp\u003eIn the other 4 groups, mice received rotenone (1.5 mg/kg 3 times / week on days 1,3,5) for consecutive 3 weeks, s.c + basel diet [18].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGroup2.\u003c/strong\u003e \u003cstrong\u003e(ROT)\u003c/strong\u003e Received ROT (1.5 mg/kg 3 times / week for consecutive 3 weeks, s.c) and served as the positive control group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGroup3. (ROT- Sinemet)\u003c/strong\u003e Received ROT + Sinemet (100mg/kg b.wt./day p.o) daily for consecutive 3 we,eks\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e19\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e, \u003c/strong\u003eas standard drug and served as standard treated group. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGroup4. (ROT - Beetroot) \u003c/strong\u003eReceived ROT + Beetroot extract 300 mg/kg b.wt./day p.o daily for consecutive 3 weeks [20]\u003cstrong\u003e, \u003c/strong\u003eand served as treated group. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGroup5. (ROT – Beetroot- Yogurt)\u003c/strong\u003e Received ROT+ beetroot extract + Yogurt (10 ml / kg b.wt daily for consecutive 3 weeks [21] and served as treated group. \u003c/p\u003e\n\u003cp\u003eFoods and drug treatments were administered one hour after the daily rotenone injections. Each mouse was weighed at the start of the study and then weekly until the experiment ended. Daily food intake was recorded, and treatments continued throughout the study. In the third week, behavioral tests were conducted, during which treatments were discontinued from the start of testing [22].\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.5\u003c/span\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eBlack Fecal Variables \u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e Feces excreted by mice during 2 h were collected after 7, 14, and 17 d of administration. Fecal number, weight, and water content were measured[\u003c/span\u003e\u003cspan dir=\"\"\u003e21\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e. \u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.6 Behavioral Tests\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.6.1 \u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003eRotarod test (RT)\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e the test was carried out in accordance with [23, 24].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.6.2 Balance beam walking (BBW)\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e the test was performed to[25, 26].\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan dir=\"\"\u003e2.6.3 Activity cage\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003e: \u003c/span\u003e\u003cspan dir=\"\"\u003ethe test was performed based on [\u003c/span\u003e\u003cspan dir=\"\"\u003e27\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan dir=\"\"\u003e2.6.4 Cylinder test\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003e: the test was performed as reported by \u003c/span\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e[\u003c/span\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003e28\u003c/span\u003e\u003cspan dir=\"\"\u003e].\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.6.5 \u003cem\u003eForced swimming test\u003c/em\u003e\u003c/span\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003e: the test was performed according to[\u003c/span\u003e\u003cspan dir=\"\"\u003e29\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan dir=\"\"\u003e2.6.6 Catalepsy test \u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e:\u003c/span\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003e the test was performed based on[\u003c/span\u003e\u003cspan dir=\"\"\u003e30\u003c/span\u003e\u003cspan dir=\"\"\u003e, \u003c/span\u003e\u003cspan dir=\"\"\u003e31\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e. \u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.6.7 \u003cem\u003eTail suspension test:\u003c/em\u003e\u003c/span\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003e the test was performed as reported by[\u003c/span\u003e\u003cspan dir=\"\"\u003e32\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e.\u003cstrong\u003e\u003cem\u003e \u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan dir=\"\"\u003e2.6.8 Hot plate\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003e: the test was carried out in accordance with, [\u003c/span\u003e\u003cspan dir=\"\"\u003e33\u003c/span\u003e\u003cspan dir=\"\"\u003e, \u003c/span\u003e\u003cspan dir=\"\"\u003e34\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e. \u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.7 Biochemical Evaluation on Mice Serum:\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.7.1 Determination of Liver Functions of Mice Serum:\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.7.1.1 Determination of Alanine aminotransferase (ALT)was according to FineTest CO, Catalogue No. EM0829. \u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.7.1.2 Determination of Aspartate aminotransferase (AST) was according to FineTest CO , Catalogue No. EM0857.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.7.2 Determination of Kidney Functions of Mice Serum:\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.7.2.1 Determination of Uric Acid was according to elabscience CO , Catalogue No. E-BC-K016-S.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.7.2.2 Determination of Creatinine was according to BioVision’s CO , Catalog No. # K625-100.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.7.2.3 Determination of Urea nitrogen was according to SunLong Biotech Co, LTD, Catalog No. SL0892Mo\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.8\u003c/span\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003e \u003cstrong\u003eBiochemical Evaluation of Mice Brain Tissues:\u003c/strong\u003e \u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.8.1 Oxidative Stress Biomarkers:\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.8.1.1 Determination of Malondialdehyde (MDA)\u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003eELISA Kit was according to life span bio sciences, inc CO, Catalog No. LS-F28474.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.8.1.2 Determination of Glutathione (GSH) Assay Kit was according to biovision CO, Catalog No. # K464-100; 100.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.8.1.3Determination of Nitric Oxide (NO) Assay Kit was according to Elabscience CO, Catalog No\u003c/span\u003e\u003cspan dir=\"\"\u003e.\u003c/span\u003e\u003cspan dir=\"\"\u003eE-BC-K035-M.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.8.2 Neuroinflammation Biomarkers:\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.8.2.1 Determination of Tumor Necrosis Factor Αlpha, TNF-A ELISA Kit was according to Bioassay Technology laboratory. CO, Catalog No\u003c/span\u003e\u003cspan dir=\"\"\u003e.\u003c/span\u003e\u003cspan dir=\"\"\u003eE0117Mo.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.8.2.2 Determination of Interleukin 6 IL-6 ELISA MAX™ was according to BioLegend’s. CO, Catalog. No. 431301.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.8.2.3 Determination of\u003c/span\u003e\u003cspan dir=\"\"\u003e Inducible nitric oxide synthase\u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003eINOS ELISA Kit was according to Novus Biologicals a Biotechne Brand. CO, NBP2-80256.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.8.3 Apoptotic Indices of Mice Brain Tissus \u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.8.3.1 Determination of Caspase 3 (CASP 3) ELISA Kit was according to Novus Biologicals a Elabscience®. CO, Catalog. No. E-EL-M0238.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.8.3.2 Determination of Alpha-synuclein (α-syn)\u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003eELISA Kit was according to Novus Biologicals a Biotechne Brand. CO,\u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003eNBP3-08174. \u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.8.3.3 Determination of Deoxyribonucleic acid DNA fragmentation\u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003ewas according to Zymoresearch Quick-gDNA™ MiniPrep kit . Catalog No. D3024.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.8.4 Neurotransmitters of Mice Brain Tissus\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.8.4.1 Determination of Acetyl cholinesterase (ACHE) ELISA Kit was according to CUSABIO\u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003eCatalog No. CSB-E17521m.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.8.4.2 Determination of Tyrosine Hydroxylase (TH) ELISA Kit was according to Novus Biologicals a Biotechne Brand. CO, NBP3-06921\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e2.8.4.3 Determination of Dopamine ELISA Kit was according to CUSABIO\u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003eCatalog No.\u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003eCSB -E08661m. \u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e2.8.5 Evaluation of α-syn on Mice Intestines Tissues \u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eDetermination of Alpha-synuclein (α-syn) ELISA Kit was according to Novus Biologicals a Biotechne Brand. CO, NBP3-08174.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e 2.9 Fecal Variables Evaluation \u003c/span\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eThe moisture content of feces was evaluated by measuring the weight of freshly collected pellets, which were then dried at room temperature until a stable weight was obtained. The percentage of water content was calculated as: [(fresh weight − dry weight) / fresh weight] × 100 [35]. \u003c/p\u003e\n\n"},{"header":"3. Analysis of Statistical Data","content":"\u003cp\u003eData are presented as mean ± standard error of the mean (SEM). Differences between groups were evaluated using one-way ANOVA, followed by Tukey’s post hoc test for multiple comparisons [36]. Statistical analyses were conducted using GraphPad Prism (version 6, USA). Values of p \u0026lt; 0.05 were considered statistically significant.\u003c/p\u003e"},{"header":"4. Results","content":"\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e4.1 \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eThe Loco motor and\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e Balance of Mice\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParkinson\u0026rsquo;s disease (PD) is a chronic neurological disorder marked by nigrostriatal degeneration, muscle stiffness, resting tremors, slowed motor activity (bradykinesia), and difficulties with balance and posture[37]\u003cstrong\u003e.\u003c/strong\u003eThe rotarod test is widely used in rodents to assess motor coordination, balance, and learning, as well as to detect neurological impairments. Modified versions improve the accuracy of preclinical drug and therapy evaluations [38]. Furthermore, the balance beam walking test serves as a functional approach to evaluate dynamic balance in experimental models [39].\u003cstrong\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eThe result present in (Figure.1) that the effect beetroot fortified yogurt as a natural source of levodopa compared to drug therapy on rotarod (Running time \u0026amp; Number of falls) and balance beam walking tests in male mice suffering from parkinson\u0026apos;s disease.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eThe result showed that the running time on the rotarod test for positive control group was much lower than negative control group. Even, there were statistical significan differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). At the same time, the number of falls on the rotarod test for positive control group was much higher than negative control group. Even, there were statistical significan differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). As for the time taken to cross the balance beam for positive control group was much higher than negative control group. Even, there were statistical significan differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eOn the other hand, the treated group with sinemet drug for running time on the rotarod test was higher than positive control group and much lower than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). While, the mean value for number of falls on the rotarod test for sinemet drug group was lower than positive control group and much higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). In addition to, the mean value for time taken to cross the balance beam test for sinemet drug group was lower than positive control group and much higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eOn contrast, the treated groups with beetroot as a natural source of levodopa and yogurt for running time on the rotarod test were much higher than positive control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).As for the number of falls on rotarod test, the treated groups with beetroot as natural source of levodopa and yogurt were much lower than positive control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). Remarkably, the treated groups with beetroot as a natural source of levodopa and yogurt for running time and number of falls on rotarod test were approximately similar results as compared to negative control group. Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eAs regard, the treated groups with beetroot as a natural source of levodopa and yogurt for time taken to cross the bar in the balance beam test were much lower than positive control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).But, the treated groups with beetroot as natural source of levodopa and yogurt for time taken to cross the bar in the balance beam test were approximately similar results as compared to negative control group. Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e4.2 Spontaneous Locomotor Activity of Mice\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eThe cylinder test is used to evaluate a rat\u0026rsquo;s independent use of its forelimbs for supporting its body against the interior walls of a cylindrical chamber [\u003c/span\u003e\u003cspan dir=\"\"\u003e40\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e.In addition, activity cages provide a practical method for monitoring spontaneous coordinated movements in both rats and mice whether tested individually or in groups as well as tracking changes in this activity over time\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"\"\u003e[\u003c/span\u003e\u003cspan dir=\"\"\u003e41\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e.\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eThe data in (Figures. 2) that the effect beetroot fortified yogurt as a natural source of levodopa compared to drug therapy on cylinder and activity cage tests in male mice suffering from Parkinson\u0026apos;s disease. The data illustrated showed that the positive control group for cylinder and activity cage tests were much lower than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eWhile, the treated group with sinemet drug for cylinder and activity cage test was higher than positive control group. But still much lower than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eConversely, the treated groups with beetroot as a natural source of levodopa and yogurt for cylinder and activity cage tests were much higher than positive control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). While, the treated group with beetroot plus yogurt for cylinder and activity cage tests were approximately normalize as compared to negative control group. Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).But, the treated group with beetroot still lower than negative control group. The best result was the group treated with beetroot as a natural source of levodopa plus yogurt. This group outperformed their counterpart who received the same beetroot as a natural source without yogurt.\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e4.3 Depression, \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eCatalepsy\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e, and Sensation of Mice\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eThe forced swim test relies on the observation that when rodents are placed in an unavoidable and aversive environment, they adopt different coping strategies, which can be classified as either active or passive responses [\u003c/span\u003e\u003cspan dir=\"\"\u003e42\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e.Similarly, the tail suspension test (TST) is employed to evaluate depressive-like behaviors in animals; in this method, mice suspended by their tails exhibit periods of immobility, interpreted as an indication of behavioral despair\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"\"\u003e[\u003c/span\u003e\u003cspan dir=\"\"\u003e32\u003c/span\u003e\u003cspan dir=\"\"\u003e,\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"\"\u003e43\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e.The catalepsy bar test is a common approach for assessing an animal\u0026rsquo;s inability to correct an externally imposed posture, typically resulting from muscular rigidity\u003c/span\u003e\u003cspan dir=\"\"\u003e[\u003c/span\u003e\u003cspan dir=\"\"\u003e44\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;. Furthermore, the hot plate test (HPT) in a dynamic setting is used to measure thermal nociception in rats by evaluating central mechanisms and determining the thermal nociceptive threshold\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"\"\u003e[\u003c/span\u003e\u003cspan dir=\"\"\u003e45\u003c/span\u003e\u003cspan dir=\"\"\u003e]\u003c/span\u003e\u003cspan dir=\"\"\u003e.\u0026nbsp;\u003c/span\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eThe result present in (Figure.3) that the effect beetroot fortified yogurt as a natural source of levodopa compared to drug therapy on some behavior tests such as forced swim, tail suspension, catalepsy and hot plate in male mice suffering from parkinson\u0026apos;s disease. The result showed that the positive control group for forced swim test was much lower than negative control group. Even, there were statistical significan differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). While, the mean values for positive control group in tail suspension, catalepsy and hot plate tests were much higher than negative control group. Even, there were statistical significan differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eOn contrast, the treated group with sinemet drug for forced swim test was higher than positive control group but still much lower than negative control groups. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). While, the means value for sinemet drug group in tail suspension, catalepsy and hot plate tests were lower than positive control group and much higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eAs regarded, the treated groups with beetroot as a natural source of levodopa and yogurt in forced swim test were much higher than positive control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).While, the treated groups with beetroot as natural source of levodopa and yogurt in tail suspension, catalepsy and hot plate tests were much lower than positive control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). Remarkably, all treated groups with natural source of levodopa and yogurt in forced swim, tail suspension, catalepsy and hot plate tests were approximately normalize as compared negative control group. Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e4.4 Liver Functions of Mice Serum\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eexposure to toxicants and impaired liver detoxification can increase susceptibility to Parkinson\u0026rsquo;s disease, as liver dysfunction may lead to neurological complications including parkinsonism [46, 47].\u003c/p\u003e\n\u003cp\u003eThe result illustrated in (Figure.4) that effect beetroot fortified yogurt as a natural source of levodopa compared to drug therapy on liver functions such as alanine amino transferase (ALT) and aspartate amino transferase (AST) in male mice suffering from parkinson\u0026apos;s disease.The result illustrated showed that ALT and AST levels for positive control group were much higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003eOn the other hand, observed that the sinemet drug group of ALT and AST levels was lower than positive control group and still much higher than negative control group. Even, there were statistical significant differences observed between them at (P\u0026lt;0.05).\u003c/p\u003e\n\u003cp dir=\"\"\u003eAs regard, the treated group with beetroot as a natural source of levodopa plus yogurt and counterpart without yogurt of ALT and AST were much lower than positive control group. Even, there were statistical significant differences observed between them at (P\u0026lt;0.05). But, the treated group with beetroot as a natural source of levodopa plus yogurt it has approximately similar result as compared to negative control group. Even, there were no statistical significant differences observed between them at (P\u0026lt;0.05).While, the treated group with beetroot as a natural source of levodopa without yogurt did not same affect.\u003cspan dir=\"\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e4.5 Renal Functions of Mice\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eSerum\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEvidence shows that even early renal disease is linked to cognitive decline, depression, and motor disturbances. CKD-related toxins and metabolic syndrome can impair dopaminergic neurons, while kidney-derived hormones like vitamin D provide neuroprotection [48].\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003eThe result present in (Figure.5) that the effect beetroot fortified yogurt as natural source of levodopa compared to drug therapy on renal functions such as urea nitrogen, creatinine and uric acid in male mice suffering from parkinson\u0026apos;s disease. The result showed that the urea nitrogen, creatinine and uric acid levels in serum male mouse for positive control group were much higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;Whereas, the data illustrated showed that the urea nitrogen, creatinine and uric acid levels for sinemet drug group were lower than positive control group. But, still much higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003eOn contrast, all treated groups with beetroot as a natural source of levodopa and yogurt for urea nitrogen, creatinine and uric acid levels were much lower than positive control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).But, the treated groups with beetroot as a natural source of levodopa plus yogurt was has approximately normal level of urea nitrogen , creatinine and uric acid as compared to negative control group. Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). While, treated group with beetroot still higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;Moreover, the result showed that the treated group with beetroot has approximately similar result as compared to sinemet drug group for uric acid level. Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u003c/span\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e4.6\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eOxidative Stress \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eof\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e Mice\u003c/span\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;\u003c/span\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eBrain Tissue\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRecent research shows that neuronal death can occur via multiple mechanisms, with oxidative stress indicated by MDA, GSH, and NO-being a major contributor [49].\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;The data illustrated in (Figure.6) that effect beetroot fortified yogurt as a natural source of levodopa compared to drug therapy on Oxidative Stress Biomarkers such as Malondialdehyde (MDA), Nitric oxide (NO) and Glutathione (GSH) in male mice suffering from parkinson\u0026apos;s disease.The data illustrated showed that the oxidative stress biomarker such as MDA and NO levels in brain tissue for positive control group were much higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). But\u003cstrong\u003e,\u003c/strong\u003e the level of GSH in brain tissue for positive control group was much lower than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;whereas, the treated group with sinemet drug for MDA and NO levels was lower than positive control group and much higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). Moreover, the treated group with sinemet drug for GSH level was much higher than positive control group. But, still lower than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eOn contrast, the treated groups with beetroot as a natural source of levodopa and yogurt for MDA and NO levels were lower than positive control group. But, the treated group with beetroot as a natural source of levodopa without yogurt still higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). While, the treated groups with beetroot plus yogurt has approximately similar result as compared to negative control group. Even, there was no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;Conversely, the data illustrated showed that GSH for the treated groups with beetroot as a natural source of levodopa and yogurt were much higher than positive control group. But, the treated group with beetroot without yogurt still lower than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e)\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eWhile, treated group with beetroot plus yogurt was has approximately normal level of GSH as compared to negative control group. Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e)\u003cstrong\u003e.\u003c/strong\u003eUnlike the groups treated with beetroot as a natural source of levodopa without yogurt,\u003c/span\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"\"\u003eit didn\u0026apos;t give the same effect.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;Moreover, the treated groups with beetroot as a natural source of levodopa has approximately similar result as compared to sinemet drug group in NO and GSH levels. Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e4.7 Neurotransmitters of Mice Brain Tissu\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParkinson\u0026rsquo;s disease is a progressive neurodegenerative disorder caused by the loss of dopamine-producing neurons in the substantia nigra [50].\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;The data illustrated in (Figure.7) that the effect beetroot fortified yogurt as a natural source of Levodopacompared to drug therapy on neurotransmitters such as Ty,rosine hydroxylase (TH), Dopamine (DOPA) and Acetylcholinesterase (ACHE) in brain tissue male mice suffering from parkinson\u0026apos;s disease.The data illustrated showed that the neurotransmitters such as TH, DOPA and ACHE levels in brain tissue for positive control group were much lower than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;While, the treated group with sinemet drug for TH, DOPA and ACHE level was higher than positive control group and much lower than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eOn contrast, all treated groups with beetroot as a natural source of levodopa and yogurt for TH, DOPA and ACHE levels were much higher than positive control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). As regard, the treated group with beetroot as a natural source of levodopa plus yogurt was has approximately similar result as compared to negative control groups. Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). While, the treated group with beetroot as a natural source of levodopa without yogurt still lower than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e4.8 Apoptotic Indices of Mice\u003c/span\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;\u003c/span\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eBrain Tissu\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eApoptosis is a programmed cell death process, with mitochondria playing a key role; reduced mitochondrial membrane permeability is an early event in this pathway [51].\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eThe data illustrated in (Figure.8) that the effect beetroot fortified yogurt as a natural source of Levodopacompared to drug therapy on apoptotic indices such as deoxyribonucleic acid (DNA), caspase-3 (Casp-3) and \u0026alpha;-synuclein (\u0026alpha;-syn) in brain tissue male mice suffering from parkinson\u0026apos;s disease.The data illustrated showed that DNA level for positive control group was much lower than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). While, the Casp-3 and \u0026alpha;-syn levels in brain tissue for positive control group were much higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003eOn the other hand, the treated group with sinemet drug for DNA level was higher than positive control group and much lower than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).But, the treated group with sinemet drug for Casp-3 and \u0026alpha;-syn levels were lower than positive control group and much higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;Concerning, the treated groups with beetroot as a natural source of levodopa and yogurt for DNA level were much higher than positive control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). But, the treated group with beetroot as a natural source of levodopa without yogurt still lower than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). While, surprisingly, the treated group with beetroot plus yogurt responded in a comparable way as compared to negative control group. Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). As for the other parameters, such as Casp-3 and \u0026alpha;-syn levels, the treated groups with beetroot as a natural source of levodopa and yogurt were much lower than positive control groups. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).However, the treated group with beetroot as a natural source of levodopa without yogurt still higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). While, the treated group with beetroot plus yogurt has approximately similar result as compared to negative control groups so alike, almost as if the induction with rotenone had no impact at all. Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eInflammatory Indices of Mice Brain Tissue\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e4.9 \u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNeuroinflammation, a CNS defense mechanism, involves overactivation of neurons and glial cells, releasing markers like TNF-\u0026alpha;, IL-1\u0026beta;, IL-10, NO, and COX-2, which contribute to the onset, diagnosis, and treatment of neurodegenerative diseases [52]\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;The result present in (Figure.9) the effect beetroot fortified yogurt as a natural source of Levodopa\u003c/span\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003ecompared to drug therapy on Inflammatory indices such as tumor necrosis factor alpha (TNF-\u0026alpha;), inducible nitric oxide synthase (Inos) and interleukin-6 (IL-6) in brain tissue male mice suffering from parkinson\u0026apos;s disease.The result illustrated showed that the inflammatory indices such as TNF-\u0026alpha;, Inos and IL-6 levels in brain tissue for positive control group were much higher than negative control group. Even, there were statistical significan differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;In relation to, the treated group with sinemet drug for TNF-\u0026alpha;, Inos and IL-6 levels were lower than positive control group and much higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;Whereas, the treated groups with beetroot as a natural source of levodopa and yogurt for TNF-\u0026alpha;, Inos and IL-6 levels were much lower than positive control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). But, the treated group with beetroot as a natural source of levodopa without yogurt still higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). While, it turns out the treated group with beetroot plus yogurt has approximately similar result as compared to negative control groups. Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e), which is interesting. As also the results showed, the treated group with beetroot has approximately similar result as compared to treated group with sinemet drug .Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eApoptotic Indices \u0026alpha;- Synuclein of Mice Intestines\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e4.10\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eImportantly, \u0026alpha;-Synuclein accumulation in the substantia nigra underlies motor impairments in PD, while non-motor symptoms, often affecting the gastrointestinal tract, can appear years earlier and may be linked to \u0026alpha;-Syn aggregates in the GIT [53].\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;The data illustrated in (Figure.10) the effect beetroot fortified yogurt as a natural source of Levodopacompared to drug therapy yogurt and drug therapy on apoptotic indices \u0026alpha;- Synuclein (\u0026alpha;-syn) in intestines tissue male mice suffering from parkinson\u0026apos;s disease. The data illustrated showed that the positive control for \u0026alpha;-syn level in intestines tissues group was much higher than negative control group. Even, there were statistical significan differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). on contrast, the treated group with sinemet drug for intestines \u0026alpha;-syn level was lower than positive control group. But, still much higher than negative control groups. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;On contrast, the treated groups with beetroot as a natural source of levodopa and yogurt for intestines \u0026alpha;-syn level were much lower than positive control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). But, the treated group with beetroot as a natural source of levodopa without yogurt still higher than negative control group. Even, there were statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e). While, the treated group with beetroot plus yogurt has approximately similar result as compared to negative control group. Even, there were no statistical significant differences observed between them at (\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e4.11 Constipation of Mice\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRecent studies suggest that intestinal microbial dysbiosis contributes to constipation by altering gut flora[15] Such dysbiosis can also impair the absorption of Parkinson\u0026rsquo;s disease medications, including levodopa [54].\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003c/strong\u003e\u003cspan dir=\"\"\u003eThe data illustrated in Table (2) that the effect beetroot fortified Yogurt as a natural source of levodopacompared to drug therapy on Number, weight (g) and water content (%) in fecal male mice suffering from parkinson\u0026apos;s disease. The data illustrated showed that the fecal number, weight and water content of the positive control group were significantly lower than negative control group. These values began to gradually decline when measured after 7, 14, and 21 days, reflecting the severity of constipation in this group. However, these differences were not statistically significant at \u003cem\u003ep \u0026lt; 0.05\u003c/em\u003e.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;On contrast, the treated group with sinemet drug for fecal number was lower than positive control group and negative control group when measured after 7, 14, and 21 days. Although the number of fecal pellets decreased compared to the positive control group. But, don\u0026rsquo;t have statistically significant differences observed at \u003cem\u003ep \u0026lt; 0.05\u003c/em\u003e.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;As regard, the treated groups with beetroot as a natural source of levodopa and yogurt for fecal number, The results were striking when measured at 7, 14 and 21 days, as some groups had fewer stools than the negative control group, and some recorded the same level of fecal count. However, it was interesting that there were groups that recorded a higher number, but the treated groups were still lower than the negative control group. But, don\u0026rsquo;t have statistically significant differences observed at \u003cem\u003ep \u0026lt; 0.05\u003c/em\u003e.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003eTable (1): \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eEffect Beet\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eroot \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eFortified Yogurt \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003eas a Natural Source of Levodopa\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e on Number, Weight (g) and Water content (%) in Fecal Male Mouse\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e Enhance in Rotenone Induced Parkinson\u0026apos;s Disease\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"\"\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e\u003cimg src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img1758703795.png\" width=\"746\" height=\"264\"\u003e\u0026nbsp;Values are expressed as mean \u0026plusmn; SE (n\u003cstrong\u003e=6\u003c/strong\u003e). \u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"5. Discussion","content":"\u003cp\u003eNutritional interventions are increasingly utilized in managing neurodegenerative disorders and may help alleviate symptoms associated with Parkinson\u0026rsquo;s disease and enhance general health. Beetroot, as a natural source of levodopa, represents a promising dietary component that could support dopaminergic function and contribute to better disease management. Compared with conventional drug therapy, such an approach may offer symptomatic relief with fewer side effects.\u003c/p\u003e\n\u003cp\u003eIn the current study, the increasing in number of falls and decreasing in running time for rotarod and time taken to cross the balance beam reduction for positive control group as compared with other control group. It may be due to injection with rotenone, which led to impaired coordination and balance, which are common symptoms of Parkinson\u0026apos;s disease. The longer time it took them to cross the balance beam indicates difficulty moving and poor muscle control, reflecting the motor dysfunction associated with Parkinson\u0026apos;s disease.To further support this explanation, it is very important to clarify these results in the light of previous findings. Several risk factors, including age, head injury, genetic predisposition, and exposure to toxins, contribute to the progression of Parkinson\u0026rsquo;s disease (PD) [55].Dopamine depletion results in motor impairments, including resting tremor, bradykinesia, postural instability, and muscle rigidity[56]. These results agreed with \u003cstrong\u003eMakav \u0026amp; Eroğlu\u003c/strong\u003e [57] study whom reported that the rotarod test showed significant differences in mean running times among the groups (P \u0026lt; 0.05). Daily oral administration of Sinemet improved movement and balance.This result agreed with \u003cstrong\u003ePerez-Pardo et al.\u003c/strong\u003e [58],study whom reported that rotenone injection significantly reduced rotarod performance and grip strength in mice, while levodopa improved these outcomes. In contrast, beetroot extract with yogurt produced greater benefits, enhancing dopamine levels and leading to superior improvements in rotarod and balance beam tests.These results agreed with \u003cstrong\u003e\u0026nbsp;Leroy et al.\u0026nbsp;\u003c/strong\u003e[59], study whom reported that this review and preliminary meta-analysis demonstrated that oral levodopa markedly enhanced performance in clinical balance assessments, such as the Berg Balance Scale (BBS) and the Postural Reaction Test (PRT), with non-significant positive trends in other tests.Also,\u003cstrong\u003e\u0026nbsp;Kwankaew \u003cem\u003eet al.\u003c/em\u003e\u0026nbsp;\u003c/strong\u003e [60], study whom reported that betanin from red beet extract restored the impaired motor performance caused by CCI surgery in mice, as confirmed by rotarod testing compared to controls.In addition to, \u003cstrong\u003eZhao et al.\u003c/strong\u003e [61], study whom reported that FMT-treated mice showed significant improvements in motor function, as reflected by better performance in the rotarod test (P \u0026lt; 0.001), adhesive removal test (P \u0026lt; 0.001), grip strength test (P \u0026lt; 0.01), and pole test (P \u0026lt; 0.001) compared to the rotenone-treated group\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e(Fig.1).\u003c/p\u003e\n\u003cp\u003eFurthermore, rotenone injection resulted in noticeable motor impairment.These results reflected in a reduced use of the forelimbs during the cylinder test and a decline in spontaneous activity cage test. These observations suggest that rotenone may negatively affect dopaminergic pathways, leading to deficits in motor coordination and exploratory behavior, reflecting the motor dysfunction associated with Parkinson\u0026apos;s disease. These results agreed with \u003cstrong\u003eAvcı et al.\u003c/strong\u003e [62]\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that rotenone significantly impaired motor coordination and balance in the cylinder test, while daily Sinemet treatment improved these functions.These results agreed with \u003cstrong\u003eGellhaar et al.\u0026nbsp;\u003c/strong\u003e[63], study whom reported that long-term L-DOPA led to abnormal repetitive behaviors in MitoPark mice, while natural levodopa with yogurt showed more stable benefits, enhancing forelimb use and exploration in cylinder and activity cage tests. These results agreed with \u003cstrong\u003eElSayed et al.\u0026nbsp;\u003c/strong\u003e[64], study whom reported that the high-dose betanin improved locomotor activity and alleviated rotenone-induced incoordination, leading to better motor function in the PD model.\u003cstrong\u003eKim et al.\u003c/strong\u003e \u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e65\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that the probiotic intake significantly improved motor function (p \u0026lt; 0.05), as confirmed by one-way ANOVA and independent t-test analyses (Fig.2).\u003c/p\u003e\n\u003cp\u003eIt is noteworthy that the observed reduction in locomoter activity, along with increased immobility, hypo-responsiveness, apathy, Loss of sensation of heat and prolonged catalepsy duration, may strongly suggest that rotenone injection is reponsaible for these behavioral impairments. This was confirmed by the results of the forced swim, tail suspension, hot plate, and catalepsy tests.These results align with previous studies demonstrating that the neurotoxic effects of rotenone induce Parkinson\u0026rsquo;s-like symptoms through mitochondrial complex inhibition and the promotion of oxidative stress.Such behavioral alterations reflect the neurodegenerative impact of rotenone on dopaminergic pathways particularly in the substantia nigra. This is one of common symptoms of parkinsons disease, known as non- motor symptoms. Consistent with a study on 109 newly diagnosed, untreated patients, non-motor symptoms such as apathy, sleep disturbances, daytime sleepiness, and constipation were reported in 60\u0026ndash;70% of cases before diagnosis, occurring more frequently than in controls. Other early symptoms included anhedonia, memory issues, sensory loss, mood changes, sweating, fatigue, pain, and gastrointestinal problems, some of which appeared over a decade before motor onset [66]\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eSymptoms of depression and anxiety may appear well in advance of the actual diagnosis.\u003c/p\u003e\n\u003cp\u003e[67].Moreover, \u003cstrong\u003eAhmed et al.\u003c/strong\u003e[68]\u003cstrong\u003e,\u003c/strong\u003e study whom reported that the Depressive-like behaviors in rotenone-treated rats were assessed by FST, TST, catalepsy, and hot plate tests, showing significantly longer immobility times (p\u0026lt;0.001) versus controls. Daily Sinemet treatment improved motor coordination and balance.These results agreed with\u003cstrong\u003eLuthra et al.\u0026nbsp;\u003c/strong\u003e[69]\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that haloperidol-induced PD models showed motor and behavioral deficits measured by catalepsy, hot plate, and swim tests. While L-DOPA provided some recovery, beetroot extract with yogurt was more effective, enhancing dopamine, improving motor function, and reducing anxiety and stiffness, as confirmed by multiple behavioral tests. These results agreed with \u003cstrong\u003eSulakhiya et al .\u003c/strong\u003e[70]\u003cstrong\u003e,\u003c/strong\u003e study whom reported that to assess the effect of BVEE on ARS-induced depressive-like behavior, immobility time in the FST was measured. ARS significantly increased immobility (p\u0026lt;0.001), confirming its depressive effect, while BVEE pretreatment markedly reduced this response (p\u0026lt;0.05; p\u0026lt;0.01 at 200 mg/kg).Moreover, \u003cstrong\u003eSulakhiya et al .\u003c/strong\u003e \u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e70\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that mice exposed to ARS showed a marked rise in immobility time in the TST (p\u0026lt;0.001), while BVEE pretreatment significantly reversed this effect at 100 mg/kg (p\u0026lt;0.05) and 200 mg/kg (p\u0026lt;0.01), demonstrating its protective role.In addition to, \u003cstrong\u003eLiu et al.\u003c/strong\u003e [71], study whom reported that restraint stress induced depressive-like behaviors and gut microbiota alterations in mice, while probiotic treatment restored microbial balance and alleviated these effects, leading to improved outcomes in FST, TST, catalepsy, and hot plate tests (Fig.3).\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eEvalution of liver function markers provides insight into systemic effects associated with Parkinson\u0026rsquo;s disease in experimental models. In this context, the resuts showed that increased in ALT and AST reduction for positive control group as compared to other control groups. It may be due to, injection with rotenone which increase Parkinson\u0026apos;s symptoms in mice. These results agreed with studies indicate that liver disease\u0026ndash;related parkinsonism may result from mechanisms such as metal overload, hyperammonemia, oxidative stress, disrupted glia-neuron balance, and neurotransmitter changes, which collectively contribute to dopaminergic neuron loss in PD [72].In addition to, \u003cstrong\u003eWang et al.\u003c/strong\u003e [73]\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u0026quot;Rotenone markedly elevated hepatic index and serum AST and ALT, and caused hepatocyte structural damage. Oral Sinemet provided only slight improvement in liver function.In this context, these results agreed with \u003cstrong\u003eKura et al.\u003c/strong\u003e [74], study whom reported that serum biochemical analysis (ALT, AST, ALP, GGT) confirmed liver function. AST was slightly higher in levodopa-treated mice, though not significantly different from controls. In contrast, beetroot as a natural levodopa source combined with yogurt showed greater positive effects on liver function than Sinemet in PD mice.These results agreed with \u003cstrong\u003eGashash \u0026amp; Wahba\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e75\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003estudy whom reported that\u003c/p\u003e\n\u003cp\u003ethe findings showed Rats receiving a diet enriched with beetroot juice showed a significant decrease (P \u0026lt; 0.05) in ALT and AST levels relative to the control group. Moreover, \u003cstrong\u003eHasan et al.\u003c/strong\u003e [76, 77]\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported \u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003ethat ALT and AST are key markers for diagnosing NAFLD, and their levels decreased with yogurt supplementation. This effect may relate to probiotic activity that normalizes liver enzymes, reduces intestinal and hepatic inflammation, and protects against liver injury (Fig.4).\u003c/p\u003e\n\u003cp\u003eAs regard, the increasing in urea nitrogen, creatinine and uric acid reduction for positive control group as compared to control groups. It may be due to, injection with rotenone which increase Parkinson\u0026apos;s disease. These results agreed with \u003cstrong\u003eUdeani et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e78\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that repeated intragastric rotenone administration caused kidney damage, evidenced by elevated BUN, uric acid, and creatinine levels. Moreover, \u003cstrong\u003eJuli et al.\u003c/strong\u003e [79]\u003cstrong\u003e,\u003c/strong\u003e study whom reported thatrotenone significantly elevated kidney function markers, including urea (p\u0026lt;0.05) and creatinine (p\u0026lt;0.001), compared to controls. Sinemet treatment showed only mild improvement in these parameters.\u003c/p\u003e\n\u003cp\u003eIn addition to,the best result was the treated group with beetroot as a natural source of levodopa plus yogurt more than counterpart without yogurt did not give the same affect. Notably, the beetroot as a natural source of levodopa and yogurt can positively enhance renal functions better than the levodopa drug (sinemet) in the serum of mice suffering from Parkinson\u0026apos;s disease. These results agreed with \u003cstrong\u003eGashash \u0026amp; Wahba\u003c/strong\u003e [75]study whom reported dietary supplementation with beetroot juice resulted in a significant reduction (P \u0026lt; 0.05) in serum urea, creatinine, and uric acid levels in rats compared with the positive control group.In addition to, \u003cstrong\u003eCheng et al.\u0026nbsp;\u003c/strong\u003e[80]\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that yogurt significantly (p\u0026lt;0.05) lowered urinary protein, serum creatinine, and BUN levels in nephritic mice compared to controls (Fig.5).\u003c/p\u003e\n\u003cp\u003eThe current findings on oxidative stress markers provide insight into the biochemical changes linked to Parkinson\u0026rsquo;s disease in the experimental group were evaluated.The increasing in NO and MDA and reduction in GSH for positive control group as compared with other control groups. It may be due to injection with rotenone which increases Parkinson\u0026apos;s disease. These results agreed with studies have shown that lifestyle and environmental factors, such as exposure to pesticides and contact with heavy metals, contribute to one in five cases of Parkinson\u0026apos;s disease, which can have a detrimental effect on oxidative stress levels in brain tissue[81]\u003cstrong\u003e.\u003c/strong\u003eAnd\u003cstrong\u003e, Abdel-Salam et al.\u0026nbsp;\u003c/strong\u003e[82]\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudywhom reported that rotenone treatment increased brain MDA and NO while depleting GSH, whereas oral Sinemet improved these oxidative stress markers in PD mice.These results agreed with \u003cstrong\u003eAyaz et al.\u0026nbsp;\u003c/strong\u003e[83]\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported \u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003ethat the rotenone elevated brain MDA and NO and reduced GSH, while Sinemet partially restored these levels in PD mice. On contrast, It was observed that the group suffering from Parkinson\u0026apos;s disease and treated with beetroot as a natural source of levodopa plus yogurt have best result for MDA and NO as compared to counterpart without yogurt. This result mean that, the beetroot as a natural source of levodopa and yogurt have beneficial therapeutic effect better than sinemet drug on oxidative stress markers in the tissue of mice with Parkinson\u0026apos;s disease. These results agreed with\u003cstrong\u003e\u0026nbsp;Sushama et al.\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e84\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that our findings support that natural levodopa sources deliver L-DOPA to the brain more effectively and sustainably than conventional antiparkinsonian drugs.Moreover, \u003cstrong\u003eThong-Asa et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e85\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e study whom reported that \u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003ebetanin extracted from red beet significantly reduced MDA levels and enhanced GSH activity (p \u0026lt; 0.05), demonstrating neuroprotective effects against rotenone-induced Parkinson\u0026rsquo;s disease in mice through its potent antioxidant action (Fig.6).\u003c/p\u003e\n\u003cp\u003eThe chemical evaluation of neurotransmitter levels highlights the harmful effects resulting from exposure to toxins on brain neurochemistry in mice suffering with Parkinson\u0026rsquo;s disease. The decreasing in TH, DOPA and ACHE reduction in positive control group as compared with other control groups. It may be due to, injection with rotenone which increase parkinson\u0026apos;s disease. These results agreed with \u003cstrong\u003eAbdel-Salam et al .\u003c/strong\u003e \u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e86\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e study whom reported that the rotenone administration resulted in a significant 57.0% reduction .in striatal tyrosine hydroxylase levels relative to the vehicle-treated control group.Moreover, \u003cstrong\u003eLandau et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e87\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that \u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003ethe rotenone reduced locomotor activity, lowered brain dopamine levels, and decreased vesicular sequestration indices (DOPAC/dopamine) compared to controls. In addition to, \u003cstrong\u003eHasan et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e88\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e study whom reported that the rotenone markedly decreased AChE activity in the cerebellum (p\u0026lt;0.05), whereas oral Sinemet improved neurotransmitter balance by elevating DOPA, AChE, and TH levels. While, administration of the oral sinemet treatment led to an improvement in the levels of DOPA, Ache, and TH.These results agreed with \u003cstrong\u003eChen et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e89\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e study whom reported that L-DOPA increased TH expression in SN and STR. On contrast, It was observed that, the groups suffering from Parkinson\u0026apos;s disease and treated with beetroot as a natural source of levodopa plus yogurt has best result for TH, DOPA and ACHE as compared with its counterpart without yogurt.This result reflected that natural beetroot as a source of levodopa and yogurt has a positive therapeutic effect better than sinemet drug on neurotransmitters in brain tissue of mice with Parkinson\u0026apos;s disease. These results agreed with \u003cstrong\u003eGhanbari et al .\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e90\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that \u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003ethe dopamine receptor gene expression in the hippocampus was significantly elevated (p\u0026le;0.001, p\u0026le;0.01) in the beetroot juice and HIIT groups versus the diabetic control, with further increases (p\u0026le;0.001) observed in the combined HIIT + beetroot group. Moreover, \u003cstrong\u003eOlasehinde et al.\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e91\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e study whom reported that BR improved an increase ACE activities were observed in the brain of rats compared control group. In addition to, \u003cstrong\u003eHsieh et al.\u003c/strong\u003e [92]\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that the daily probiotic supplementation markedly enhanced gait, balance, and coordination compared with the sham group, while maintaining TH-positive cells in the substantia nigra. These results suggest that prolonged probiotic intake protects dopaminergic neurons and mitigates motor impairments in MitoPark PD mice (Fig.7).\u003c/p\u003e\n\u003cp\u003eEvaluation of DNA integrity, Caspase-3, and \u0026alpha;-synuclein levels highlights the cellular damage and apoptosis associated with Parkinson\u0026rsquo;s disease in mice.The decreasing in DNA and increasing in Casp-3 and \u0026alpha;-syn reduction in positive control group as compared with other control groups. It may be due to, injection with rotenone which increase Parkinson\u0026apos;s disease. These results agreed with \u003cstrong\u003eBalakrishnan et al.\u003c/strong\u003e \u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e93\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that the chronic rotenone administration induced PD-like pathology, marked by oxidative stress, elevated \u0026alpha;-synuclein, and increased expression of apoptotic proteins caspase-3, -8, and -9.Moreover, \u003cstrong\u003eKhalil et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e94\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that the rotenone-treated mice exhibited elevated TNF-\u0026alpha;, IL-1\u0026beta;, DNA damage, and caspase-3 expression, while oral Sinemet improved DNA integrity, Casp-3, and \u0026alpha;-synuclein levels, alleviating PD symptoms.These results agreed with \u003cstrong\u003eMotawi et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e95\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported thatSinemet significantly reduced caspase-3 fragmentation and \u0026alpha;-synuclein levels (p\u0026lt;0.0001) compared to rotenone, showing approximately 70% improvement in these markers.On contrast, It was observed that the groups suffering from Parkinson\u0026apos;s disease and treated with beetroot as a natural source of levodopa plus yogurt has best result for DNA, Casp-3 and \u0026alpha;-syn as compared to its counterpart without yogurt.This results reflected that, the beetroot as a natural source of levodopa and yogurt have a positive therapeutic effect better than sinemet drug on apoptotic indices in brain tissue of mice with Parkinson\u0026apos;s disease. These results agreed with \u003cstrong\u003ePhukan et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e96\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003estudywhom reported that the red beetroot extract, rich in betanin, reduced abnormal \u0026alpha;‑synuclein accumulation in dopaminergic neurons of PD mice.Also, \u003cstrong\u003eWang et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e97\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e study whom reported that our results indicated that probiotics of \u003cem\u003eL. plantarum\u003c/em\u003e DP189 reduced the \u0026alpha;-SYN accumulation in SNin brain mice in comparison with control group (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05) (Fig.8).\u003c/p\u003e\n\u003cp\u003eMoreover, the resuts showed that the increased in TNF-\u0026alpha;, Inos and IL-6 levels reduction in positive control group as compared with other control groups. It may be due to, injection with rotenone which increase parkinson\u0026apos;s disease. These results agreed with\u003cstrong\u003e\u0026nbsp;Siracusa et al.\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e22\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that \u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eiNOS expression in the SN was significantly increased 28 days after rotenone administration compared to controls.Moreover, \u003cstrong\u003eZhang et al.\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e98\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e study whom reported that the rotenone significantly increased pro-inflammatory cytokines (IL-6, IL-1\u0026beta;, TNF-\u0026alpha;, IFN-\u0026gamma;, PGE2) and NO in the SN (p\u0026lt;0.01), while arctigenin was assessed for its effect on this neuroinflammation.On the other hand, administration of oral sinemet treatment resulted in a noticeable reduction in the levels of TNF-\u0026alpha;, iNOS, and IL-6, indicating an attenuation of neuroinflammatory responses in Parkinson\u0026rsquo;s disease.These results agreed with \u003cstrong\u003eMotawi et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e95\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that the regarding to IL-6 level showed significant decrease with sinemet (each \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) treatments as compared with the rotenone group. Moreover, \u003cstrong\u003eAbdel-Sattar et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e99\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that the mice treated with L-Dopa/carbidopa showed low levels of the inflammatory markers TNF-\u0026alpha;, NF-\u0026kappa;B and IL-1\u0026beta; in the striatum compared with rotenone group.The observed results allowed us to simply conclude that groups suffering from Parkinson\u0026apos;s disease and treated with beetroot as a natural source of levodopa plus yogurt showed the best outcomes for TNF-\u0026alpha;, iNOS, and IL-6 compared to its counterpart without yogurt.It reflected that, natural source of levodopa and yogurt have a positive therapeutic effect better than sinemet drug on inflammatory cytokines in brain tissue of mice with Parkinson\u0026apos;s disease. These result agree with \u003cstrong\u003eKhan et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e100\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e study whom reported that the negative control group showed a significant rise (P \u0026lt; 0.0001) in brain inflammatory cytokines compared to normal controls. Conversely, betalains and chloroquine groups exhibited a marked reduction (P \u0026lt; 0.0001), with the betalains protective group restoring cytokine levels toward normal values.In addition to, \u003cstrong\u003eAno et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e101\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e study whom reported that extracts from the surface of fermented dairy products suppressed microglial TNF-\u0026alpha; production in a dose-dependent manner, enhancing anti-inflammatory activity and A\u0026beta; phagocytosis, whereas extracts from the interior or unfermented products had no effect (Fig.9).\u003c/p\u003e\n\u003cp\u003eThe present observations regarding \u0026alpha;-synuclein accumulation highlight the potential involvement of the gut\u0026ndash;brain axis in the development of Parkinson\u0026rsquo;s disease.This result supported the It may be due to, injection with rotenone leads tothe presence of pathogenic \u0026alpha;-syn in both the gut and brain highlights the possible contribution of the enteric nervous system (ENS) to the etiology of PD. The hypothesis that \u0026alpha;-syn pathology may propagate from the gut to the brain, leading to degeneration of the nigrostriatal dopaminergic pathway, remains highly compelling.These result agreed with\u003cstrong\u003e\u0026nbsp;Chen et al.\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e102\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that the rotenone significantly increased intestinal \u0026alpha;‑syn levels in h\u0026alpha;‑syn+/\u0026ndash; mice, showing a 2.3-fold rise at 6 months and a 2-fold rise at 12 months compared to age-matched controls. Moreover, administration of oral sinemet treatment appeared to mitigate \u0026alpha;-synuclein accumulation, suggesting its potential in modulating the gut\u0026ndash;brain axis and reducing neurodegeneration in Parkinson\u0026rsquo;s disease. This improvement indicates that sinemet treatment can partially counteract the effects of rotenone-induced pathogenic \u0026alpha;-syn in both the gut and brain mice. These results agreed with \u003cstrong\u003ePellegrini et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e103\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudywhom reported that the L-DOPA/BE treatment improved colonic motor activity and normalized immunopositivity, with beetroot plus yogurt showing the greatest reduction in intestinal \u0026alpha;‑syn in PD mice compared to beetroot alone.Subsequently, it is reflected that, beetroot as a natural source of levodopa has a positive therapeutic effect better than sinemet drug on apoptotic indices such as \u0026alpha;- synuclein in intestines tissue of mice with Parkinson\u0026apos;s disease. These results agreed with \u003cstrong\u003eKo et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e104\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that the red beet RP and BP altered gut microbiota composition and SCFA production differently across enterotypes, with the Bifidobacterium cluster showing significantly reduced alpha diversity and distinct microbial changes.In addition to, \u003cstrong\u003ePerazza et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e105\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e study whom reported that shannon index and PCoA analyses showed that dairy fermentation significantly modulated gut microbiota, with WT and LRKO mice fed fermented products exhibiting distinct \u0026alpha;‑diversity and metagenomic profiles compared to nonfermented diets(Fig.10) .\u003c/p\u003e\n\u003cp\u003eRegarding gastrointestinal function, the results showed that the positive control group showed significantly reduced fecal count, weight, and water content compared with the negative control group.Quite simply, it can be said that this occurred due to rotenone injection, which caused constipation in mice with Parkinson\u0026apos;s disease, thereby contributing to impaired dopamine production and, consequently, reduced motor activity. These results were approximately agreed with\u003cstrong\u003e\u0026nbsp;Chu et al.\u003c/strong\u003e [106]\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that rotenone intake led to a significant reduction in fecal pellet weight and water content compared with the control group in PD mice (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05). During the treatment period, a marked change in stool shape was observed, from separate pellets to more compact, sometimes elongated, ribbon-like masses. This change in shape led to a decrease in the number of counted pellets. While, fecal weight and water content were higher than positive control group and much lower than negative control groups.These reflected that for sinemet drug group began to gradually increase when measured after 7, 14, and 21 days. This indicates that levodopa had a weak effect in improving the symptoms of constipation. However, these differences were not statistically significant at \u003cem\u003ep \u0026lt; 0.05\u003c/em\u003e. These result was approximately agreed with \u003cstrong\u003eRadisavljevic et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e107\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that chronic oral L-DOPA plus carbidopa (LDCD) treatment reduced whole-gut transit time (p\u0026lt;0.0001), alleviating constipation-like symptoms in mice.On contrast, the number of fecal pellets decreased as compared to the positive control group, this is not necessarily indicative of worsening constipation. During the treatment period, a marked change in stool form was observed, from separate pellets to denser clumps. Sometimes longer, ribbon-like. This change in shape resulted in a decrease in the number of counted granules. This change is likely related to the effect of various natural sources of levodopa and yogurt, which improve fecal consistency and increase its viscosity, resulting in a less disintegrated and more cohesive fecal, a positive sign in the treatment of constipation. Thus, there is no exacerbation of Parkinson\u0026apos;s disease symptoms as compared with the fecal weight and water content. But, without statistical significance. At the same time, fecal weight and water content were much higher than positive control group. And lower than negative control group. These mean\u003csup\u003e,\u003c/sup\u003es that the treated groups with beetroot as a natural source of levodopa and yogurt began to gradually increase gradually and significantly when measured after 7, 14, and 21 days. Altogether, it was observed that, groups suffering from Parkinson\u0026apos;s disease and treated with beetroot plus yogurt has best result for water content and fecal weight as compared to it is counterpart without yogurt. Subsequently, it was reflected that the beetroot as a natural source of levodopa and yogurt have a positive therapeutic effect better than sinemet drug for fecal weight and water content of mice with Parkinson\u0026apos;s disease. These results were approximately agreed with \u003cstrong\u003eZhao et al.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e61\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003estudy whom reported that the rotenone caused weight loss, motor deficits, and GI dysfunction in mice, while FMT treatment significantly improved fecal output and alleviated these PD-related symptoms.Also, \u003cstrong\u003eMahran et al.\u003c/strong\u003e\u003cstrong\u003e[\u003c/strong\u003e\u003cstrong\u003e53\u003c/strong\u003e\u003cstrong\u003e]\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e study whom reported thatexperimental diets, especially PBM, significantly (p\u0026le;0.05) normalized constipation-related parameters in rats without causing diarrhea, supporting the traditional use of PP and BP for LOP-induced constipation (Table.1).\u003c/p\u003e"},{"header":"6. Conclusion","content":"\u003cp\u003eBeetroot-fortified yogurt, as a natural source of levodopa, showed superior effects compared to conventional drug treatment, by enhancing brain dopaminergic neurons and improving motor symptoms in Parkinson\u0026rsquo;s-induced mice.Moreover, its antioxidant properties provided additional neuroprotection and symptom relief. These findings indicate that yogurt enriched with beetroot has the potential to be developed as a safe functional product, and cost-effective dietary strategy for Parkinson\u0026rsquo;s disease management.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePD: Parkinson\u0026apos;s disease; ROT: Rotenone; DMSO: dimethyl sulfoxide;L-DOPA:Levodopa; ALT:alanine aminotransferase; AST: aspartate aminotransferase; MDA: Malondialdehyde; GSH: Glutathione; NO: Nitric Oxide;TNF: Tumor Necrosis Factor \u0026Alpha;lpha; IL-6: Interleukin 6; INOS: Inducible nitric oxide synthase; CASP 3: Caspase 3; \u0026alpha;-syn: Alpha-synuclein; DNA: Deoxyribonucleic acid;ACHE: Acetyl cholinesterase; TH: Tyrosine Hydroxylase; DOPA: Dopamine.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eI would like to sincerely thank and extend my appreciation to Ain Shams University, the Faculty of Specific Education, and the National Research Centre for their valuable support and for providing the necessary facilities to accomplish this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was entirely self-funded by the corresponding author and other authors and no external funding was obtained. and is intended for Open Access publication under the Springer Nature agreement with Ain Shams University. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study are available from the corresponding author \u0026nbsp;upon reasonable request. All datasets and materials used in the analysis and interpret- action of results can be shared to ensure transparency and reproducibility in line with the journal\u003csup\u003e\u0026apos;\u003c/sup\u003es data sharing policy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Informations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHome Economics Department, Faculty of Specific Education, Ain Shams University, Cairo, Egypt\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Radwa A. Shaheen, Ereny W. Nagib \u0026amp; Usama E. Mostafa\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePharmacology Department, Institute of Medical Research and Clinical Studies,\u003c/p\u003e\n\u003cp\u003eNational Research Centre, Giza, Egypt\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003eMohamed M. Amin \u0026amp; Rehab R. Hegazy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding Author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRAS.\u003c/strong\u003e\u003cspan dir=\"\"\u003e\u0026nbsp;She conceived and designed the study, performed the experimental work, and wrote the first draft of the manuscript.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u003c/strong\u003es\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMMA.\u003c/strong\u003e He conducted some behavioral tests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEWN.\u003c/strong\u003e Help write manuscript draft.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRRH\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"\"\u003e.\u003c/span\u003e\u003c/strong\u003e She performed statistical analyses, contributed to data interpretation, conducted some behavioral tests, and provided technical support during the experiment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUEM.\u003c/strong\u003e Contributed to the study design, critically reviewed the manuscript, and assisted in writing the manuscript and interpreting the results.\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe experimental protocol was reviewed and approved by the Ethics Committee of the Faculty of Specific Education, Ain Shams University. All animal procedures were conducted in accordance with the guidelines of the committee and international standards for the care and use of laboratory animals.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eORCID:\u0026nbsp;\u003c/strong\u003ehttps://orcid.org/0009-0005-8957-9534\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e G. Naik, R.G. Shaikh, S.P. Dipankar, J.K. Thilaka, H. Sharma, D. Sharma, Neuroprotective Effects of Natural Plant Extracts (Ginkgo biloba, Curcuma longa, and Withania somnifera) in Parkinson\u0026rsquo;s Disease Models: A Meta-Analysis, Disease and Health: Research Developments, (2025) 114.\u003c/span\u003e DOI: https://doi.org/10.9734/bpi/dhrd/v8/4833\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e C. Angeloni, D. Vauzour, Natural products and neuroprotection, in, MDPI, 2019, pp. 5570.\u003c/span\u003e \u003cstrong\u003ehttps://doi.org/10.3390/ijms20225570\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e D. Georgescu, O.E. Ancusa, L.A. Georgescu, I. Ionita, D. Reisz, Nonmotor gastrointestinal disorders in older patients with Parkinson\u0026rsquo;s disease: is there hope?, Clinical interventions in aging, (2016) 1601-1608. https://doi.org/10.2147/CIA.S106284\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e S.-C. Fu, L.-C. Shih, P.-H. Wu, Y.-C. Hsieh, C.-H. Lee, S.-H. Lin, H. Wang, Exploring the causal effect of constipation on Parkinson\u0026rsquo;s disease through mediation analysis of microbial data, Frontiers in Cellular and Infection Microbiology, 12 (2022) 871710. https://doi.org/10.3389/fcimb.2022.871710\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e A. Segal, Y. Zlotnik, K. Moyal-Atias, R. Abuhasira, G. Ifergane, Fecal microbiota transplant as a potential treatment for Parkinson\u0026apos;s disease\u0026ndash;a case series, Clinical Neurology and Neurosurgery, 207 (2021) 106791. https://doi.org/10.1016/j.clineuro.2021.106791\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e E. Cassani, G. Privitera, G. Pezzoli, C. Pusani, C. Madio, L. Iorio, M. Barichella, Use of probiotics for the treatment of constipation in Parkinson\u0026apos;s disease patients, Minerva gastroenterologica e dietologica, 57 (2011) 117-121.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e M.N. Han, D.I. Finkelstein, R.M. McQuade, S. Diwakarla, Gastrointestinal dysfunction in Parkinson\u0026rsquo;s disease: current and potential therapeutics, Journal of personalized medicine, 12 (2022) 144.\u003c/span\u003e \u003cstrong\u003ehttps://doi.org/10.3390/jpm12020144\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e M.U. Rehman, A.F. Wali, A. Ahmad, S. Shakeel, S. Rasool, R. Ali, S.M. Rashid, H. Madkhali, M.A. Ganaie, R. Khan, Neuroprotective strategies for neurological disorders by natural products: an update, Current neuropharmacology, 17 (2019) 247-267. DOI: https://doi.org/10.2174/1570159X16666180911124605\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e B. Chen, J. Zhao, R. Zhang, L. Zhang, Q. Zhang, H. Yang, J. An, Neuroprotective effects of natural compounds on neurotoxin-induced oxidative stress and cell apoptosis, Nutritional neuroscience, 25 (2022) 1078-1099. https://doi.org/10.1080/1028415X.2020.1840035\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e V.S. Nade, L.A. Kawale, S.S. Zambre, A.B. Kapure, Neuroprotective potential of Beta vulgaris L. in Parkinson\u0026apos;s disease, Indian journal of pharmacology, 47 (2015) 403-408. DOI: 10.4103/0253-7613.161263\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eE. Hadipour, A. Taleghani, N. Tayarani‐Najaran, Z. Tayarani‐Najaran, Biological effects of red beetroot and betalains: A review, Phytotherapy research, 34 (2020) 1847-1867. https://doi.org/10.1002/ptr.6653\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eO. Giampaoli, C. Ieno, F. Sciubba, M. Spagnoli, A. Miccheli, A. Tomassini, W. Aureli, L. Fattorini, Metabolic biomarkers of red beetroot juice intake at rest and after physical exercise, Nutrients, 15 (2023) 2026. https://doi.org/10.3390/nu15092026\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eR. Sunnadeniya, A. Bean, M. Brown, N. Akhavan, G. Hatlestad, A. Gonzalez, V.V. Symonds, A. Lloyd, Tyrosine hydroxylation in betalain pigment biosynthesis is performed by cytochrome P450 enzymes in beets (Beta vulgaris), PloS one, 11 (2016) e0149417. https://doi.org/10.1371/journal.pone.0149417\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eP. Hemarajata, J. Versalovic, Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation, Therapeutic advances in gastroenterology, 6 (2013) 39-51. https://doi.org/10.1177/1756283X12459294\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eJ. Wang, Q. Liang, Q. Zhao, Q. Tang, A.F. Ahmed, Y. Zhang, W. Kang, The effect of microbial composition and proteomic on improvement of functional constipation by Chrysanthemum morifolium polysaccharide, Food and Chemical Toxicology, 153 (2021) 112305.\u003c/span\u003e https://doi.org/10.1016/j.fct.2021.112305\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eH.-J. Wu, E. Wu, The role of gut microbiota in immune homeostasis and autoimmunity, Gut microbes, 3 (2012) 4-14. https://doi.org/10.4161/gmic.19320\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eY. Belkaid, T.W. Hand, Role of the microbiota in immunity and inflammation, Cell, 157 (2014) 121-141. \u003c/span\u003ehttp://dx.doi.org/10.1016/j.cell.2014.03.011\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eN.F. Abdelkader, H.A. Farid, E.R. Youness, O.M. Abdel-Salam, H.F. Zaki, The role of KATP channel blockade and activation in the protection against neurodegeneration in the rotenone model of Parkinson\u0026apos;s disease, Life Sciences, 257 (2020) 118070. https://doi.org/10.1016/j.lfs.2020.118070\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eH.R.A. Salem, A. El-Raouf, E.M. Saleh, K. Shalaby, Influence of hesperidin combined with Sinemet on genetical and biochemical abnormalities in rats suffering from Parkinson\u0026rsquo;s disease, Life Sci J, 9 (2012) 930-945.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eG. Albasher, T. Albrahim, N. Alsultan, S. Alfaraj, M.S. Alharthi, R.B. Kassab, A.E. Abdel Moneim, Red beetroot extract mitigates chlorpyrifos-induced reprotoxicity associated with oxidative stress, inflammation, and apoptosis in rats, Environmental Science and Pollution Research, 27 (2020) 3979-3991.\u003c/span\u003e https://doi.org/10.1007/s11356-019-07009-6 \u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eT. Li, Q. Yan, Y. Wen, J. Liu, J. Sun, Z. Jiang, Synbiotic yogurt containing konjac mannan oligosaccharides and Bifidobacterium animalis ssp. lactis BB12 alleviates constipation in mice by modulating the stem cell factor (SCF)/c-Kit pathway and gut microbiota, Journal of Dairy Science, 104 (2021) 5239-5255. https://doi.org/10.3168/jds.2020-19449\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eR. Siracusa, M. Scuto, R. Fusco, A. Trovato, M.L. Ontario, R. Crea, R. Di Paola, S. Cuzzocrea, V. Calabrese, Anti-inflammatory and anti-oxidant activity of Hidrox\u0026reg; in rotenone-induced Parkinson\u0026rsquo;s disease in mice, Antioxidants, 9 (2020) 824. https://doi.org/10.3390/antiox9090824\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eJ.B. Carroll, A.L. Southwell, R.K. Graham, J.P. Lerch, D.E. Ehrnhoefer, L.-P. Cao, W.-N. Zhang, Y. Deng, N. Bissada, R.M. Henkelman, Mice lacking caspase-2 are protected from behavioral changes, but not pathology, in the YAC128 model of Huntington disease, Molecular neurodegeneration, 6 (2011) 59.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eM. Wada, M.J. Ang, P.D. Weerasinghe-Mudiyanselage, S.-H. Kim, J.-C. Kim, T. Shin, C. Moon, Behavioral characterization in MPTP/p mouse model of Parkinson\u0026rsquo;s disease, Journal of Integrative Neuroscience, 20 (2021) 307-320.\u003c/span\u003e https://doi.org/10.31083/j.jin2002030\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eL.Y. Chen, S.H. Tai, Y.C. Hung, S.Y. Huang, Z.C. Kuo, A.H. Lee, H.H. Hsu, T.S. Wu, E.J. Lee, Anti‐oxidative and anti‐inflammatory effects of Ginkgo biloba extract (EGb761) on hindlimb skeletal muscle ischemia\u0026ndash;reperfusion injury in rats, Physiological reports, 12 (2024) e16050. https://doi.org/10.14814/phy2.16050\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eJ. Liu, X. Lv, T. Ye, M. Zhao, Z. Chen, Y. Zhang, W. Yang, H. Xie, L. Zhan, L. Chen, Microbiota-microglia crosstalk between Blautia producta and neuroinflammation of Parkinson\u0026apos;s disease: A bench-to-bedside translational approach, Brain, Behavior, and Immunity, 117 (2024) 270-282. https://doi.org/10.1016/j.bbi.2024.01.010\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eM. Kujawska, M. Jourdes, Ł. Witucki, M. Karaźniewicz-Łada, M. Szulc, A. G\u0026oacute;rska, P.Ł. Mikołajczak, P.-L. Teissedre, J. Jodynis-Liebert, Pomegranate juice ameliorates dopamine release and behavioral deficits in a rat model of Parkinson\u0026rsquo;s disease, Brain Sciences, 11 (2021) 1127. https://doi.org/10.3390/brainsci11091127\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eA.D. Nadeev, K.A. Kritskaya, E.I. Fedotova, A.V. Berezhnov, \u0026laquo;One Small Step for Mouse\u0026raquo;: High CO2 Inhalation as a New Therapeutic Strategy for Parkinson\u0026rsquo;s Disease, Biomedicines, 10 (2022) 2832. https://doi.org/10.3390/biomedicines10112832\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eM.E. Crupi R, Marino A, La Spada G, Bramanti P, Cuzzocrea, S.E. S, Melatonin treatment mimics the antidepressant action in chronic corticosterone-treated mice., J Pineal Res(2): ((2010)) 123\u0026ndash;129.49 https://doi.org/10.1111/j.1600-079X.2010.00775.x\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e S.J.R. Ali, P.S. (2016). Effect of monocrotophos, an organophosphorus insecticide, on the striatal dopaminergic system in a mouse model of Parkinson\u0026rsquo;s disease. Toxicology and Industrial Health 32(7): 1153-1165. doi. org/10.1177/0748233714547733.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eP.R. Sanberg, Bunsey, M. D., Giordano, M., \u0026amp; Norman, A. B. (1988). The catalepsy test: its ups and downs. Behavioral neuroscience, 102(5), 748.\u0026rlm;.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eF. Khakpai, Ebrahimi-Ghiri, M., Alijanpour, S., \u0026amp; Zarrindast, M.R .(2019). Ketamine-induced antidepressant like effects in mice: a possible involvement of cannabinoid system. Biomed Pharmacother 112:108717. \u003c/span\u003ehttps://doi.org/10.1016/j.biopha.2019.108717\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eM. Dolatshahi, Farbood, Y., Sarkaki, A., Mansouri, S. M. T., \u0026amp; Khodadadi, A. (2015). Ellagic acid improves hyperalgesia and cognitive deficiency in 6-hydroxidopamine induced rat model of Parkinson\u0026rsquo;s disease. Iranian journal of basic medical sciences, 18(1), 38.\u0026rlm;\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eF. Faivre, S\u0026aacute;nchez-Catal\u0026aacute;n, M. J., Dovero, S., Bido, S., Joshi, A., Bezard, E., \u0026amp; Barrot, M. (2020). Ablation of the tail of the ventral tegmental area compensates symptoms in an experimental model of Parkinson\u0026apos;s disease. Neurobiology of Disease, 139, 104818.\u0026rlm; \u003c/span\u003ehttps://doi.org/10.1016/j.nbd.2020.104818\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eJ. Wu, Cheng, Yan, Zhang, Rong, Liu, Dong, Luo, Yu-Mei, Chen, Kun-Lun, Ren., \u0026amp; Song-Zhang. (2017). P2Y1R is involved in visceral hypersensitivity in\u003cspan dir=\"\"\u003e \u003c/span\u003erats with experimental irritable bowel syndrome. World J. Gastroenterol. 23 (34), 6339 https://doi.org/10.3748/wjg.v23.i34.6339.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eO.J.M.c.u.r.s.T.\u003c/span\u003e Dunn. (1964). Multiple Comparisons Using Rank Sums. \u003cem\u003eTechnometrics\u003c/em\u003e, \u003cem\u003e6\u003c/em\u003e(3), 241\u0026ndash;252. https://doi.org/10.1080/00401706.1964.10490181\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e Y.H. Leem, Park, J. S., Park, J. E., Kim, D. Y., \u0026amp; Kim, H. S. (2022). Neurogenic effects of rotarod walking exercise in subventricular zone, subgranular zone, and substantia nigra in MPTP-induced Parkinson\u0026rsquo;s disease mice. Scientific reports, 12(1), 10544.\u0026rlm;\u003c/span\u003e https://doi.org/10.1038/s41598-022-14823-5\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eH.M. Shan, Maurer, M. A., \u0026amp; Schwab, M. E. (2023). Four-parameter analysis in modified\u003cspan dir=\"\"\u003e \u003c/span\u003eRotarod test for detecting minor motor deficits in mice. BMC biology, 21(1), 177.\u003c/span\u003e https://doi.org/10.1186/s12915-023-01679-y\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eT. Hortob\u0026aacute;gyi, Vetrovsky, T., Uematsu, A., Sanders, L., da Silva Costa, A. A., Batistela, R. A., \u0026amp; Toll\u0026aacute;r, J. (2023). Beam walking as a new measure of dynamic balance\u003cspan dir=\"\"\u003e \u003c/span\u003eto predict falls.\u003c/span\u003e DOI: https://doi.org/10.21203/rs.3.rs-3268679/v1\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eA.D. Bj\u0026ouml;rklund, S. B. (2019). The amphetamine induced rotation test: a re-assessment of its use as a tool to monitor motor impairment and functional recovery in rodent models of Parkinson\u0026rsquo;s disease. Journal of Parkinson\u0026rsquo;s Disease, 9(1), 17-29.\u0026rlm;. https://doi.org/10.3233/JPD-181525\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eFilipiuc, (2024). JWH-182: a safe and effective synthetic c*nnabinoid for chemotherapy-induced neuropathic pain in preclinical models, Scientific reports\u003c/span\u003e . https://doi.org/10.1038/s41598-024-67154-y\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eM. Khorasani, Kiasalari, Z., Ghasemi, R., Fakour, M., Keshtkar, S., \u0026amp; Roghani, M. (2020). The effect of nobiletin on performance of rats in forced swimming and elevated plus maze tests in intranigral lipopolysaccharide rat model of Parkinson\u0026apos;s disease. Journal of Basic and Clinical Pathophysiology, 8(1), 28-34.\u0026rlm;\u003c/span\u003eDOI 10.22070/JBCP.2020.4355.1115\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eM. Ebrahimi-Ghiri, Shahini, F., \u0026amp; Zarrindast, M. R. (2021). The effect of URB597, exercise or their combination on the performance of 6-OHDA mouse model of Parkinson disease in the elevated plus maze, tail suspension test and step-down task. Metabolic Brain Disease, 36(8), 2579-2588.\u0026rlm;\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eK.R. Luciani, Frie, J. A., \u0026amp; Khokhar, J. Y. (2020). An open source automated bar test for measuring catalepsy in rats. Eneuro, 7 (3). \u003c/span\u003edoi.org/10.1523/ENEURO.0488-19.2020\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eG.C.D. Nascimento, Bariotto-Dos-Santos, K., Leite-Panissi, C. R. A., Del-Bel, E. A., \u0026amp; Bortolanza, M. (2018). Nociceptive response to L-DOPA-induced dyskinesia in hemiparkinsonian\u003cspan dir=\"\"\u003e \u003c/span\u003erats. Neurotoxicity Research, 34, 799-807.\u0026rlm; \u003c/span\u003ehttps://doi.org/10.1007/s12640-018-9896-0\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eA.B. Tryc, Goldbecker, A., Berding, G., R\u0026uuml;mke, S., Afshar, K., Shahrezaei, G. H., \u0026amp; Weissenborn, K. (2013). Cirrhosis-related Parkinsonism: prevalence, mechanisms and response to treatments. Journal of Hepatology, 58(4), 698-705.\u0026rlm; \u003c/span\u003ehttps://doi.org/10.1016/j.jhep.2012.11.043\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eJ.S. Bajaj, Gentili, A., Wade, J. B., \u0026amp; Godschalk, M. (2022). Specific challenges in geriatric cirrhosis and hepatic encephalopathy. Clinical Gastroenterology and Hepatology, 20(8), S20-S29.\u0026rlm; \u003c/span\u003ehttps://doi.org/10.1016/j.cgh.2022.04.035\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eY.S. Kim, A.S Lee, H.J. Hur, S.H. Lee, H.J.Na, \u0026amp; M.J. Sung, (2023). Renoprotective effect of Chrysanthemum coronarium L. extract on adenine-induced chronic kidney disease in mice. Pharmaceuticals, 16(7), 1048.\u003cspan dir=\"\"\u003e\u0026rlm; \u003c/span\u003ehttps://doi.org/10.3390/ph16071048\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eX. Dong-Chen, Yong, C., Yang, X., Chen-Yu, S., \u0026amp; Li-Hua, P. (2023). \u0026quot;Signaling pathways in Parkinson\u0026apos;s disease: molecular mechanisms and therapeutic interventions\u0026quot;. Signal Transduction and Targeted Therapy. 8 (1): 1\u0026ndash;18. doi:10.1038/s41392-023-01353-3. ISSN 2059-3635. PMC 9944326. PMID 36810524.\u003c/span\u003e https://doi.org/10.1038/s41392-023-01353-3\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eS. Latif, Jahangeer, M., Razia, D. M., Ashiq, M., Ghaffar, A., Akram, M., \u0026amp; Ansari, M. A. (2021). Dopamine in Parkinson\u0026apos;s disease. Clinica chimica acta, 522, 114-126. https://doi.org/10.1016/j.cca.2021.08.009\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eH. Wang, C. Zhang, M. Li, C. Liu, J. Wang, X. Ou, Y. Han, Antimicrobial peptides mediate apoptosis by changing mitochondrial membrane permeability, International Journal of Molecular Sciences, 23 (2022) 12732. https://doi.org/10.3390/ijms232112732\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eA. Rauf, H. Badoni, T. Abu-Izneid, A. Olatunde, M.M. Rahman, S. Painuli, P. Semwal, P. Wilairatana, M.S. Mubarak, Neuroinflammatory markers: key indicators in the pathology of neurodegenerative diseases, Molecules, 27 (2022) 3194. https://doi.org/10.3390/molecules27103194\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eM. Mahran, M. Elkabary, H. Saad, Potential Laxative Effects of Dried Plums (Prunes) and Red Beetroot on Loperamide-Induced Constipation in Adult Rats, Journal of Home\u003cspan dir=\"\"\u003e \u003c/span\u003eEconomics-Menofia University, 34 (2024) 175-203.DOI 10.21608/MKAS.2024.291926.1316\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eH. Doi, R. Sakakibara, M. Sato, T. Masaka, M. Kishi, A. Tateno, F. Tateno, Y. Tsuyusaki, O. Takahashi, Plasma levodopa peak delay and impaired gastric emptying in Parkinson\u0026apos;s disease, Journal of the neurological sciences, 319 (2012) 86-88. https://doi.org/10.1016/j.jns.2012.05.010\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eX.-S. Zeng, W.-S. Geng, J.-J. Jia, Neurotoxin-induced animal models of Parkinson disease: pathogenic mechanism and assessment, ASN neuro, 10 (2018) 1759091418777438.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eJ.D. Guo, X. Zhao, Y. Li, G.R. Li, X.L. Liu, Damage to dopaminergic neurons by oxidative stress in Parkinson\u0026apos;s disease, International journal of molecular medicine, 41 (2018) 1817-1825. https://doi.org/10.3892/ijmm.2018.3406\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eM. Makav, H.A. Eroğlu, Recuperative effect of estrogen on rotenone-induced experimental model of Parkinson\u0026rsquo;s disease in rats, Environmental Science and Pollution Research, 28 (2021) 21266-21275. https://doi.org/10.1007/s11356-020-11985-5\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e P. Perez-Pardo, L.M. Broersen, T. Kliest, N. Van Wijk, A. Attali, J. Garssen, A.D. Kraneveld, Additive effects of levodopa and a neurorestorative diet in a mouse model of Parkinson\u0026rsquo;s disease, Frontiers in Aging Neuroscience, 10 (2018) 237. https://doi.org/10.3389/fnagi.2018.00237\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eT. Leroy, R.J. Baggen, N. Lefeber, N. Herssens, P. Santens, M. De Letter, L. Maes, K. Bouche, A. Van Bladel, Effects of oral levodopa on balance in people with idiopathic Parkinson\u0026rsquo;s disease, Journal of Parkinson\u0026rsquo;s Disease, 13 (2023) 3-23. https://doi.org/10.3233/JPD-223536\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eN. Kwankaew, H. Okuda, A. Aye‐Mon, T. Ishikawa, K. Hori, P. Sonthi, Y. Kozakai, N. Ozaki, Antihypersensitivity effect of betanin (red beetroot extract) via modulation of microglial activation in a mouse model of neuropathic pain, European Journal of Pain, 25 (2021) 1788-1803. https://doi.org/10.1002/ejp.1790\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eZ. Zhao, J. Ning, X.-q. Bao, M. Shang, J. Ma, G. Li, D. Zhang, Fecal microbiota transplantation protects rotenone-induced Parkinson\u0026rsquo;s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis, Microbiome, 9 (2021) 226.\u003c/span\u003e https://doi.org/10.1186/s40168-021-01107-9\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eB. Avcı, C. G\u0026uuml;naydın, T. G\u0026uuml;ven\u0026ccedil;, C.K. Yavuz, N. Kuruca, S.S. Bilge, Idebenone ameliorates rotenone-induced Parkinson\u0026rsquo;s disease in rats through decreasing lipid peroxidation, Neurochemical Research, 46 (2021) 513-522.\u003c/span\u003e https://doi.org/10.1007/s11064-020-03186-w\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eS. Gellhaar, D. Marcellino, M. Abrams, D. Galter, Chronic L‐DOPA induces hyperactivity, normalization of gait and dyskinetic behavior in\u003cspan dir=\"\"\u003e \u003c/span\u003eMitoPark mice, Genes, Brain and Behavior, 14 (2015) 260-270. https://doi.org/10.1111/gbb.12210\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eM.H. ElSayed, H.M. Atif, M.A. Eladl, S.M. Elaidy, A.M. Helaly, F.A. Hisham, N.E. Farag, N.M. Osman, A.T. Ibrahiem, H.W. Khella, Betanin improves motor function and alleviates experimental\u003cspan dir=\"\"\u003e \u003c/span\u003eParkinsonism via downregulation of TLR4/MyD88/NF-\u0026kappa;B pathway: Molecular docking and biological investigations, Biomedicine \u0026amp; Pharmacotherapy, 164 (2023) 114917. https://doi.org/10.1016/j.biopha.2023.114917\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eJ. Kim, B.-E. Yoon, Y.K. Jeon, Effect of treadmill exercise and probiotic ingestion on motor coordination and brain activity in adolescent mice, in: Healthcare, MDPI, 2020, pp. 7. https://doi.org/10.3390/healthcare9010007\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eC. Pont‐Sunyer, A. Hotter, C. Gaig, K. Seppi, Y. Compta, R. Katzenschlager, N. Mas, D. Hofeneder, T. Br\u0026uuml;cke, A. Bay\u0026eacute;s, The O nset of N onmotor S ymptoms in P arkinson\u0026apos;s disease (T he ONSET PD S tudy), Movement Disorders, 30 (2015) 229-237. https://doi.org/10.1002/mds.26077\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eH. Chen, E.A. Burton, G.W. Ross, X. Huang, R. Savica, R.D. Abbott, A. Ascherio, J.N. Caviness, X. Gao, K.A. Gray, Research on the premotor symptoms of Parkinson\u0026rsquo;s disease: clinical and etiological implications, Environmental health perspectives, 121 (2013) 1245-1252. https://doi.org/10.1289/ehp.1306967\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eO.G. Ahmed, M. Mahmoud, A.A. Abdelhamid, Behavioral Evaluation of rotenone model of Parkinson\u0026rsquo;s disease in male Wistar rats, Sohag Medical Journal, 24\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003e.\u003c/span\u003e\u003cspan dir=\"\"\u003e(2020) 8-14.\u003c/span\u003e DOI: 10.21608/smj.2020.21596.1089\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eP.M. Luthra, S.K. Barodia, R. Raghubir, Antagonism of haloperidol-induced swim impairment in L-dopa and caffeine treated mice: a pre-clinical model to study Parkinson\u0026apos;s disease, Journal of neuroscience methods, 178 (2009) 284-290. https://doi.org/10.1016/j.jneumeth.2008.12.019\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eK. Sulakhiya, V.K. Patel, R. Saxena, J. Dashore, A.K. Srivastava, M. Rathore, Effect of Beta vulgaris Linn. leaves extract on anxiety-and depressive-like behavior and oxidative stress in mice after acute restraint stress, Pharmacognosy research, 8 (2016) 1. doi: 10.4103/0974-8490.171100\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eQ.F. Liu, H.-M. Kim, S. Lim, M.-J. Chung, C.-Y. Lim, B.-S. Koo, S.-S. Kang, Effect of probiotic administration on gut microbiota and depressive behaviors in mice, DARU Journal of Pharmaceutical Sciences, 28 (2020) 181-189.\u003c/span\u003e https://doi.org/10.1007/s40199-020-00329-w \u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eS. Li, Y. Zhua, X. Liu, Parkinsonism in liver diseases or dysfunction, Medicina Cl\u0026iacute;nica, 163 (2024) 461-468.\u003c/span\u003e https://doi.org/10.1016/j.medcli.2024.04.022\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eH. Wang, M. Huo, Y. Jin, Y. Wang, X. Wang, W. Yu, X. Jiang, Rotenone induces hepatotoxicity in rats by activating the mitochondrial pathway of apoptosis, Toxicology Mechanisms and Methods, 32 (2022) 510-517. https://doi.org/10.1080/15376516.2022.2049940\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eA.U. Kura, B. Saifullah, P.-S. Cheah, M.Z. Hussein, N. Azmi, S. Fakurazi, Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite, Nanoscale Research Letters, 10 (2015) 105. DOI 10.1186/s11671-015-0742-5\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eE.A. Gashash, H. Wahba, The efficiency of red grapes and beetroot juice as nutrients for improving blood glucose levels, renal function, liver enzymes, and immunity factors, \u003cspan dir=\"\"\u003eمجلة\u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003eدراسات\u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003eوبحوث\u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003eالتربية\u003c/span\u003e\u003cspan dir=\"\"\u003e \u003c/span\u003e\u003cspan dir=\"\"\u003eالنوعية\u003c/span\u003e\u003cspan dir=\"\"\u003e, 11 (2025) 138-154.\u003c/span\u003e DOI: 10.21608/JSEZU.2025.402707\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eS. Hasan, M.A.I. Amin, M. Mia, S. Khatun, Y. Arafat, M.R. Gofur, M.M. Islam, M.E. Hosen, K.S. Almaary, G. Fentahun Wondmie, Yogurt Supplementation Can Ameliorate Fatty Liver Diseases and Metabolic Syndrome in High Fat‐Induced Conditions in Mice, Food Science \u0026amp; Nutrition, 13 (2025) e4650. https://doi.org/10.1002/fsn3.4650\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eM.R. Shahein, E.S.H. Atwaa, H.A. Radwan, A.A. Elmeligy, A.A. Hafiz, A. Albrakati, E.K. Elmahallawy, Production of a yogurt drink enriched with Golden berry (Physalis pubescens L.) juice and its therapeutic effect on hepatitis in rats, Fermentation, 8 (2022) 112. https://doi.org/10.3390/fermentation8030112\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eG.O. Udeani, G.-M. Zhao, Y.G. Shin, J.W. Kosmeder Ii, C.W. Beecher, A.D. Kinghorn, R.M. Moriarty, R.C. Moon, J.M. Pezzuto, Pharmacokinetics of deguelin, a cancer chemopreventive agent in rats, Cancer chemotherapy and pharmacology, 47 (2001) 263-268.DOI 10.1007/s002800000187\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eJ. Jain, W. Hasan, P. Biswas, R.S. Yadav, D. Jat, International Journal of Human Anatomy.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eL. Cheng, P. Yao, H. Wang, Q. Yuan, X. Wang, W. Feng, F. Sun, Q. Wang, Effects of Lactobacillus plantarum HFY15 on lupus nephritis in mice by regulation of the TGF-\u0026beta;1 signaling pathway, Drug Design, Development and Therapy, (2022) 2851-2860. https://doi.org/10.2147/DDDT.S363974\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eB.L. Santos-Lobato, Towards a methodological uniformization of environmental risk studies in Parkinson\u0026rsquo;s disease, npj Parkinson\u0026apos;s Disease, 10 (2024) 86.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eO.M. Abdel-Salam, M.E.-S. El-Shamarka, N. Shaffie, Neuroprotective effect of capsaicin against rotenone-induced Parkinson\u0026rsquo;s disease in mice, International Journal of Halal Research, 6 (2024) 1-11. DOI : https://doi.org/10.18517/ijhr.6.1.1-14.2024\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eM. Ayaz, F. Anwar, U. Saleem, I. Shahzadi, B. Ahmad, A. Mir, T. Ismail, Parkinsonism attenuation by antihistamines via downregulating the oxidative stress, histamine, and inflammation, ACS omega, 7 (2022) 14772-14783.\u003c/span\u003e https://doi.org/10.1021/acsomega.2c00145 ACS \u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eA.P. Sushama, Onkar, A. A., Shripad, N. S., \u0026amp; Jyoti, P. J. (2013). Biological sources of L-DOPA: An alternative approach. *Advances in Parkinson\u0026apos;s Disease, 2*(3), 81\u0026ndash;87. https://doi.org/10.4236/apd.2013.23016\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eW. Thong-Asa, S. Jedsadavitayakol, S. Jutarattananon, Benefits of betanin in rotenone-induced Parkinson mice, Metabolic brain disease, 36 (2021) 2567-2577.https://doi.org/10.1007/s11011-021-00826-0\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eO.M. Abdel-Salam, S.M.Y. Morsy, E.R. Youness, N.N. Yassen, A.A. Sleem, The effect of low dose amphetamine in rotenone-induced toxicity in a mice model\u003cspan dir=\"\"\u003e \u003c/span\u003eof Parkinson\u0026rsquo;s disease, Iranian Journal of Basic Medical Sciences, 23 (2020) 1207. doi: 10.22038/ijbms.2020.45175.10524\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eR. Landau, R. Halperin, P. Sullivan, Z. Zibly, A. Leibowitz, D.S. Goldstein, Y. Sharabi, The rat rotenone model reproduces the abnormal pattern of central catecholamine metabolism found in Parkinson\u0026apos;s disease, Disease Models \u0026amp; Mechanisms, 15 (2022) dmm049082. https://doi.org/10.1242/dmm.049082\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eW. Hasan, R.K. Kori, J. Jain, R.S. Yadav, D. Jat, Neuroprotective effects of mitochondria‐targeted curcumin against rotenone‐induced oxidative damage in cerebellum of mice, Journal of biochemical and molecular toxicology, 34 (2020) e22416. https://doi.org/10.1002/jbt.22416\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eX. Chen, Z. Wang, W. Yang, Y. Fu, Levodopa improves behavioral deficits of mice with Parkinson\u0026apos;s disease symptoms via curbing NLRP3 inflammasome activation and enhancing tyrosine hydroxylase levels in the striatum and substantia nigra, Journal of integrative neuroscience, 23 (2024) 2. https://doi.org/10.31083/j.jin2301002\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eP. Ghanbari, S. Khajehzadeh, A. Sayyed, D. Raeisi, O. Salehi, The effect of high intensity interval training with beetroot (Beta vulgaris) juice supplementation on serotonin and dopamine receptors expression, anxiety and depression in middle-aged diabetic rats, Avicenna Journal of Phytomedicine, 12 (2022) 627. doi: 10.22038/AJP.2022.20895\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eT.A. Olasehinde, S.I. Oyeleye, C.U. Ibeji, G. Oboh, Beetroot supplemented diet exhibit anti-amnesic effect via modulation of cholinesterases, purinergic enzymes, monoamine oxidase and attenuation of redox imbalance in the brain of scopolamine treated male rats, Nutritional Neuroscience, 25 (2022) 1011-1025. https://doi.org/10.1080/1028415X.2020.1831260\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eT.-H. Hsieh, C.-W. Kuo, K.-H. Hsieh, M.-J. Shieh, C.-W. Peng, Y.-C. Chen, Y.-L. Chang, Y.-Z. Huang, C.-C. Chen, P.-K. Chang, Probiotics alleviate the progressive deterioration of motor functions in a mouse model of Parkinson\u0026rsquo;s disease, Brain sciences, 10 (2020) 206. https://doi.org/10.3390/brainsci10040206\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eR. Balakrishnan, D. Vijayraja, T. Mohankumar, D. Manimaran, P. Ganesan, D.-K. Choi, N. Elangovan, Isolongifolene mitigates rotenone-induced dopamine depletion and motor deficits through anti-oxidative and anti-apoptotic effects in a rat model of Parkinson\u0026apos;s disease, Journal of chemical neuroanatomy, 112 (2021) 101890. https://doi.org/10.1016/j.jchemneu.2020.101890 \u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eW.K. Khalil, N. Assaf, S.A. ElShebiney, N.A. Salem, Neuroprotective effects of bee venom acupuncture therapy against rotenone-induced oxidative stress and apoptosis, Neurochemistry international, 80 (2015) 79-86. https://doi.org/10.1016/j.neuint.2014.11.008\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eT.K. Motawi, N.A. Sadik, M.A. Hamed, S.A. Ali, W.K. Khalil, Y.R. Ahmed, Potential therapeutic effects of antagonizing adenosine A2A receptor, curcumin and niacin in rotenone-induced Parkinson\u0026rsquo;s disease mice model, Molecular and cellular biochemistry, 465 (2020) 89-102. Molecular and Cellular https://doi.org/10.1007/s11010-019-03670-0\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eB.C. Phukan, R. Roy, R. Paul, M.K. Mazumder, J. Nath, P. Bhattacharya, A. Borah, Traversing through the cell signaling pathways of neuroprotection by betanin: Therapeutic relevance to Alzheimer\u0026rsquo;s Disease and Parkinson\u0026rsquo;s Disease, Metabolic Brain Disease, 38 (2023) 805-817.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eL. Wang, Z. Zhao, L. Zhao, Y. Zhao, G. Yang, C. Wang, L. Gao, C. Niu, S. Li, Lactobacillus plantarum DP189 reduces \u0026alpha;-SYN aggravation in MPTP-induced Parkinson\u0026rsquo;s disease mice via regulating oxidative damage, inflammation, and gut microbiota disorder, Journal of agricultural and food chemistry, 70 (2022) 1163-1173. https://doi.org/10.1021/acs.jafc.1c07711\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e N. Zhang, D. Dou, X. Ran, T. Kang, Neuroprotective effect of arctigenin against neuroinflammation and oxidative stress induced by rotenone, Rsc Advances, 8 (2018) 2280-2292. DOI: 10.1039/C7RA10906G\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003eE. Abdel-Sattar, E.A. Mahrous, M.M. Thabet, D.M.Y. Elnaggar, A.M. Youssef, R. Elhawary, S.A. Zaitone, C. Rodr\u0026iacute;guez-P\u0026eacute;rez, A. Segura-Carretero, R.H. Mekky, Methanolic extracts of a selected Egyptian Vicia faba cultivar mitigate the oxidative/inflammatory burden and afford neuroprotection in a mouse model of Parkinson\u0026rsquo;s disease, Inflammopharmacology, 29 (2021) 221-235. nfammopharmacology (\u003c/span\u003e https://doi.org/10.1007/s10787-020-00768-6\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e S.A. Khan, M.N. Alsulami, A.A. Alsehimi, M.S. Alzahrani, D.A. Mosule, H.H. Albohiri, Beta vulgaris Betalains Mitigate Parasitemia and Brain Oxidative Stress Induced by Plasmodium berghei in Mice, Pharmaceuticals, 17 (2024) 1064. doi: 10.3390/ph17081064\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e Y. Ano, M. Ozawa, T. Kutsukake, S. Sugiyama, K. Uchida, A. Yoshida, H. Nakayama, Preventive effects of a fermented dairy product against Alzheimer\u0026rsquo;s disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity, PloS one, 10 (2015) e0118512. https://doi.org/10.1371/journal.pone.0118512\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e J. Gao, Identifying Probiotics that Modulate Mitophagy in Models of Mitochondrial Dysfunction, in, University of Toronto (Canada), 2023.\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e C. Pellegrini, L. Antonioli, R. Colucci, E. Tirotta, D. Gentile, C. Ippolito, C. Segnani, G. Levandis, S. Cerri, F. Blandini, Effects of L-DOPA/benserazide co-treatment on colonic excitatory cholinergic motility and enteric inflammation following dopaminergic nigrostriatal neurodegeneration, Neuropharmacology, 123 (2017) 22-33. https://doi.org/10.1016/j.neuropharm.2017.05.016\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e G.-P. Ko, H. Jo, J. Kim, J.S. Kim, K.-H. Boo, C.S. Kim, Enterotype-Specific Effects of Red Beetroot (Beta vulgaris L.) Powder and Betanin on Human Gut Microbiota: A Preliminary Study Based on In Vitro Fecal Fermentation Model, Life, 14 (2024) 1391. doi: 10.3390/life14111391\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e L.R. Perazza, N. Daniel, M.-J. Dubois, G. Pilon, T.V. Varin, M. Blais, J.L.M. Gonzales, M. Bouchard, C. Asselin, M. Lessard, Distinct effects of milk-derived and fermented dairy protein on gut microbiota and cardiometabolic markers in diet-induced obese mice, The Journal of Nutrition, 150 (2020) 2673-2686. https://doi.org/10.1093/jn/nxaa217\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e C. Chu, L. Yu, Y. Li, H. Guo, Q. Zhai, W. Chen, F. Tian, Lactobacillus plantarum CCFM405 against rotenone-induced Parkinson\u0026rsquo;s disease mice via regulating gut microbiota and branched-chain amino acids biosynthesis, Nutrients, 15 (2023) 1737. https://doi.org/10.3390/nu15071737\u003c/span\u003e\u003c/li\u003e\n\u003cli\u003e\u003cspan dir=\"\"\u003e N. Radisavljevic, A. Metcalfe-Roach, M. Cirstea, M.M. Tabusi, T. Bozorgmehr, H. Bar-Yoseph, B.B. Finlay, Microbiota-mediated effects of Parkinson\u0026rsquo;s disease medications on Parkinsonian non-motor symptoms in male transgenic mice, Msphere, 9 (2024) e00379-00323. \u003c/span\u003ehttps://doi.org/10.1128/msphere.00379-23\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Parkinson’s disease, Rotenone, Beetroot, Yogurt, levodopa and Behavioral tests","lastPublishedDoi":"10.21203/rs.3.rs-7602198/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7602198/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/em\u003e Parkinson’s disease (PD) is a common neurodegenerative disorder; however there is still a lacks of effective and safe treatments for it. Beetroot is a unique plant containing rich in betalains. It has shown protecting dopamine cells effects.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eAim:\u003c/strong\u003e\u003c/em\u003e To evaluate the effect of beetroot fortified yogurt on PD symptoms in mice compare to levodopa drug.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/em\u003e PD was induced in adult male Swiss albino mice by rotenone through 9 subcutaneous injections 1.5 mg/kg; 3 times / week. Locomotor activity was assessed by behavioral tests, and some biochemical analyses were conducted.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/em\u003e \u0026nbsp;Beetroot fortified yogurt improved locomotor activity and reduced PD markers such as, oxidative stress biomarkers, Neurotransmitters, Apoptotic Indices, Inflammatory Indices, liver and kidney functions and Constipation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/em\u003e Red beet fortified yogurt and inhibited the development of PD in mice better than levodopa drug, which may be partly responsible for decreased oxidative damage and enhances dopamine production in brain.\u003c/p\u003e","manuscriptTitle":"Beetroot (Beta vulgaris) - Fortified Yogurt as a Natural Source of Levodopa Enhances in Rotenone – induced Parkinson's Disease in Mice","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-24 09:10:26","doi":"10.21203/rs.3.rs-7602198/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"004d971e-01e2-433b-88e7-bcdf1d199c08","owner":[],"postedDate":"September 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-24T09:10:26+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-24 09:10:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7602198","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7602198","identity":"rs-7602198","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}