The effect of propolis and honey on oxidant and antioxidant parameters and D-glucose induced hyperglycemia, acute kidney injury and proteinuria in rats

The effect of propolis and honey on oxidant and antioxidant parameters and D-glucose induced hyperglycemia, acute kidney injury and proteinuria in rats | 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 Article The effect of propolis and honey on oxidant and antioxidant parameters and D-glucose induced hyperglycemia, acute kidney injury and proteinuria in rats Soumaya Touzani, Noori Al-Waili, Hassan Laaroussi, Abderrazak Aboulghazi, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2697406/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 Propolis and honey possess antioxidant, hypoglycemic, and antiproteinuric effects. The study aimed to explore the effect of propolis, honey, and their combination against D-glucose-induced hyperglycemia, acute kidney injury, liver injury, dyslipidemia, and changes in the oxidants and antioxidants in renal, hepatic, and pancreatic tissues. The chemical analysis and antioxidant content of propolis and honey were studied. The inhibitory effect of propolis and honey on alpha-amylase and alpha-glucosidase activity was studied. The study included five groups of rats, four groups treated with D-glucose and one group untreated. The D-glucose treated group (diabetic group) was divided into 1-4 groups. In addition to D-glucose, groups 2,3, and 4 were treated with propolis, honey, and a combination of propolis and honey respectively. Blood glucose levels, liver and renal function tests, urine protein and electrolytes, oxidant and antioxidant parameters, and histopathological changes in hepatic, renal, and pancreatic tissues were studied. Treatment with D-glucose continued for seven weeks, and with other interventions for the following 3 weeks. Propolis has a higher level of total protein and antioxidant activity than honey while honey contains higher carbohydrate levels. Honey has a higher alpha-amylase and glucosidase inhibitory activity than propolis. D-glucose caused a significant elevation of blood glucose, insulin, HOMA, blood urea, creatinine, lipid parameters, liver enzymes, and urine protein level. It significantly increases MDA and decreases antioxidant parameters in pancreatic, hepatic, and renal tissues. D-glucose caused histopathological changes in hepatic, renal, and pancreatic tissues. Propolis, honey, and their combination significantly ameliorated these changes. Propolis, honey, or their combination treated hyperglycemia, acute kidney injury, proteinuria, liver injury, and dyslipidemia, induced by D-glucose, most likely, by antioxidant activity and alpha-amylase and alpha-glucosidase inhibitory activity. Biological sciences/Biochemistry Health sciences/Medical research Honey propolis D-glucose antioxidant diabetes kidney liver pancreas Figures Figure 1 Figure 2 Figure 3 Introduction Honey and propolis are bee natural products that showed various biological and therapeutic activities in pre-clinical and clinical studies conducted in animals and humans. Honey ameliorates diabetic nephropathy caused by streptozotocin [ 1 ].]. It prevents hyperglycemia and ameliorates renal and hepatic injury in diabetic mice [ 2 ]. In addition to its hypoglycemic effect, honey prevents dyslipidemia and histopathological changes in pancreatic islets in diabetic rats [ 3 ]. It was proposed that honey content of antioxidants, zinc, copper, and selenium might play a role in honey`s hypoglycemic effect [ 4 , 5 ]. Regarding kidney function, honey protects renal and hepatic injuries and increases urine volume in lead and CCl4 intoxication [ 6 – 8 ]. Honey demonstrated diuretic, natriuretic and kaliuretic activity [ 9 ]. Induction of diabetes in rats increased oxidative stress and decreased antioxidants in the kidneys tissue which were attenuated with the use of honey [ 10 ]. A recent study showed that honey in doses of 1,2 and 3 grams /kg b.wt for 16 weeks ameliorates renal dysfunction, metabolic acidosis, and renal histological changes in high fructose diet-fed Wistar rats [ 11 ]. In a clinical study, honey has a beneficial effect on kidney function and inflammatory mediators [ 12 ]. Honey has been mentioned in the Holy books, the Talmud, both the old and new testaments of the Bible, and the Holy Quran as a healer of diseases. In the Surat Al-Nahel (The Bee) it says: And the LORD taught the bee to build its cells in mountains, on tree, and in men’s habitations, then to eat of all the fruits of the earth and find with skill the spacious paths of its LORD, there issues from within their bodies a drink of varying colors, wherein is healing for men, verily in this is a sign for those who give thought . Data showed that propolis has antioxidant and renal and hepatic protective activities [ 9 , 13 , 14 ]. In earlier observations, propolis demonstrated higher antioxidant activity than honey [ 9 ]. In diabetic rats, propolis significantly improves blood glucose levels, increases insulin sensitivity, and decreases oxidative stress in diabetic rats [ 15 – 17 ]. Propolis has an anti-advanced glycation end-products activity [ 17 , 18 ]. Interestingly, we found that propolis decreases urinary protein excretion and prevents acute kidney and liver injuries caused by ethylene glycol ingestion in rats [ 19 ]. Propolis and honey are great candidates to be used in the management of diabetes, and their combination might have a synergistic or additive effect [ 9 , 20 ]. Therefore, the present study evaluated honey and propolis's effect and their combination collected from Moroccan areas on blood glucose and insulin level, acute kidney injury (AKI), liver injury, proteinuria, and lipid parameters in D-glucose-induced diabetic rats. The investigations included studying physicochemical characteristics, antioxidant content, and antioxidant activity of propolis and honey samples. Results Table 1 showed that propolis has significantly higher total protein and antioxidant activity than honey while carbohydrate is higher in honey than in propolis (p<0.05). The honey sample contains fructose 34,22 ± 1,92 g/100g, glucose 23.34 ± 2.52 g/100 g, maltose and sucrose 2.11 ± 0.07 g/100g, and HMF 9.729.72±0.11. Furfural was not detected. Regarding phenolic compounds, table 2 demonstrated various phenolic compounds in both honey and propolis. Compared to honey, propolis has higher concentrations of vanillic acid, naringin, hesperidin, quercetin, rutin, and kaempferol, Table 3 showed that honey has higher alpha-amylase inhibitory activity than propolis and acarbose and higher alpha-glucosidase inhibitory activity than propolis (P<0.05). Effect of interventions on blood glucose, insulin, HOMA-IR, HOMA-B, and QUICKI D-glucose caused a significant elevation of blood glucose, insulin, HOMA-B, and HOMA-IR ( Table 4 ). The use of propolis, honey, and a combination of propolis and honey with D-glucose decreased these parameters toward the control levels (P<0.05). The combined use of propolis and honey with D-glucose showed a significantly stronger effect than the use of propolis with D-glucose or honey with D-glucose. Effect of interventions on liver function tests and lipid profile Table 5 showed that D-glucose increases total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein (LDL), and decreases high-density lipoprotein (HDL), these changes markedly improved with the use of propolis, honey, and their combination with D-glucose; the use of hone and propolis with D-glucose showed a stronger effect compared to propolis or honey (p<0.05). D-glucose increased liver enzymes, TB, and decreased albumin level (p<0.05). The combined use of honey, propolis, or their combination with D-glucose significantly improved these changes toward the control values. The use of both honey and propolis in rats treated with D-glucose showed a stronger effect than the effects seen with the use of propolis or honey (p<0.05). Effect of interventions on AKI induced by D-glucose and blood and urine electrolytes. D-glucose increased blood urea, serum creatinine, serum uric acid, urine protein, and urine uric acid ( Table 6 ). The use of propolis or honey in rats receiving D-glucose significantly ameliorates the effect of D-glucose on renal function tests by decreasing urine protein, blood urea, and serum creatinine. The use of a combination of propolis and honey demonstrated a stronger effect than propolis or honey individually (P<0.05). Table 7 demonstrated that D-glucose causes a significant lowering of serum sodium and potassium that was ameliorated with the use of propolis, honey, or their combination. Effects of the interventions on antioxidant parameters, protein, and MDA levels in pancreatic, liver, and kidney tissues D-glucose caused a significant decrease in glutathione (GHS), glutathione peroxidase (GPx), catalase (CAT), and protein and an increase in malondialdehyde (MDA) levels in pancreatic, liver, and kidney tissues, P<0.05 ( Tables 8-10 ). The use of propolis, honey, or their combination significantly ameliorated D-glucose effects by increasing antioxidant parameters and protein and decreasing MDA levels. Table 11 showed the quantity of oxidants and antioxidants in the kidney, liver, and pancreatic tissues. Pancreas tissue contains a higher amount of GHS than the liver and kidney and the liver tissue contains a higher amount of MDA than other tissues. Histological changes caused by the interventions. Figures 1,2 and 3 demonstrated some of the changes caused by d-glucose with and without the use of honey, propolis, or a combination of honey and propolis. It seems that honey and propolis alleviate the effects of D-glucose on the histopathological changes in the liver, kidney, and pancreatic tissues. Discussion The data showed that treatment with honey, propolis, and their combination significantly alleviated the adverse effect of D-glucose-induced hyperglycemia on blood glucose and insulin level, and acute kidney and liver injuries. Honey and propolis decreased hyperglycemia, reduced insulin blood level, ameliorated AKI, proteinuria, and the elevation of hepatic enzymes. The interventions prevented crossly histological changes in the renal, hepatic, and pancreatic tissues after the induction of hyperglycemia in rats. Interestingly, the combination of honey and propolis was more potent than the effect of honey or propolis individually. The data from the chemical analysis demonstrated the presence of phenols and flavonoids in honey and propolis samples which possess a strong antioxidant capacity. Propolis contains a high amount of protein while honey contains a high amount of carbohydrates. Honey explores a higher alpha-amylase and alpha-glucosidase inhibitory activity than propolis. IC50 in the DPPH test was higher in propolis compared to honey and total antioxidant activity was higher in propolis compared to honey, which indicated higher antioxidant capacity in propolis compared to honey. The total phenol content of 17 various Moroccan honey samples including Arbutus unedo honey ranges between 16.38 mg GAE/100g (citrus honey) to 92.37 mg GAE/100 (thyme honey) [ 20 , 21 ]. Therefore, the phenolic content in the multiflora honey sample collected from hives installed in the Sefrou region, Morocco (28.54 ± 1.04 mg GAE/g) is higher than the other Moroccan honey samples. The content of multiflora honey tested in the present study is higher than Manuka honey`s phenolic content (71 mg GAE/100g) and Iranian honey’s phenolic content (193.8 mg GAE/100g honey) [ 22 ]. The data showed that multiflora honey from Sefrou region did not contain epicatechin which is rarely found in honey samples. However, our earlier study showed that thyme vulgaris honey and Arbutus undeo honey collected from Morocco contain epicatechin [ 20 , 23 ]. The physicochemical characterization and the antioxidant content of honey samples vary, and the presented result showed that multiflora honey's analyzed parameters were following the requirements of the International Honey Commission 2009 and codex standard for honey [ 25 , 26 ]. Propolis contains different types of phenolic acids, and 14 compounds were identified using UPLC/DAD. All the compounds detected were phenolic acids and their ester derivatives. The results showed that naringin, hesperidin, rosmarinic acid, and kaempferol were the most abundant in the propolis samples test in the present study. The analysis conducted in another propolis sample from Morocco revealed that pinobanksin-3- O -acetate, pinocembrin, and caffeic acid phenylethyl ester were the most abundant phenolics [ 20 ]. The results of the DPPH test demonstrated that propolis showed a higher scavenging capacity against DPPH than honey. Administration of D- glucose caused diabetes with an elevation of blood glucose and insulin levels. It did not cause much change in pancreatic tissue such as a decrease in the islets of Langerhans. The administration of honey and propolis after induction of diabetes markedly restores hyperglycemia and hyperinsulinemia toward the normal range. D-glucose significantly increased HOMA-IR and decreased QUIKI. Therefore, D-glucose increased blood glucose level by increasing insulin resistance and decreasing insulin sensitivity. These changes were less evident with the use of honey and propolis because of decreasing insulin levels and HOMA-IR. In clinical settings, it was found that honey can reduce hyperglycemia and insulin resistance in diabetic patients [ 26 ]. The antioxidant ameliorates oxidative stress in the pancreatic tissues and stimulates insulin secretion [ 27 ]. Honey contains antioxidants and fructose which might be responsible for the hypoglycemic effect [ 28 ]. Complex carbohydrates are hydrolyzed by pancreatic alpha-amylase and alpha-glucosidase enzymes, resulting in the production of glucose which is absorbed by the intestine. In our study, honey and propolis have alpha-glucosidase and alpha-amylase inhibitory activity; honey has higher inhibitory activity than propolis. Honey and propolis contain flavonoids that have alpha-amylase and glucosidase inhibitory activity ( 29 ). Other studies confirm that honey and flavonoids possess significant alpha-amylase and alpha-glucosidase inhibitory activity [ 30 – 32 ]. These findings might help explain the beneficial effect of honey and propolis on diabetes and might help in the prevention of diabetes Mellitus. Proteinuria and kidney diseases are common complications of diabetes. Acute hyperglycemia could cause AKI and oxidative stress [ 33 ]. D-glucose administration and hyperglycemia caused AKI, proteinuria, an increase in urine uric acid, and a considerable decrease in the urinary excretion of creatinine. AKI was evident by a significant elevation of serum creatinine and blood urea. Interestingly, the use of honey or propolis significantly ameliorated AKI and proteinuria, and the combination of both showed a better effect. The data showed that honey, propolis, and their combination alleviate hyperglycemia-induced AKI. We have found that propolis prevents proteinuria, crystalluria, and AKI caused by ethylene glycol ingestion in rats [ 19 ]. Furthermore, propolis has higher antioxidant activity than honey [ 9 , 20 ]. Other studies showed phenols and flavonoids improving AKI, renal fibrosis, and inflammation [ 34 , 35 ]. Therefore, such findings might partly explore honey and propolis protective effect mechanisms of action against hyperglycemia-induced AKI and proteinuria. Hyperglycemia in rats causes liver toxicity and elevation of liver enzymes level [ 36 ]. The present result showed that hyperglycemia induced by D-glucose causes acute liver injury; there was a significant evaluation of liver enzymes and total bilirubin associated with a decrease in serum albumin level. We found similar results in streptozotocin-induced hyperglycemia [ 20 ]. Interestingly, the use of propolis and honey prevented liver injury. The protective effects might be related to high levels of antioxidants in honey and propolis. Hyperglycemia reduces the levels of antioxidants, increases levels of oxidants, and causes oxidation-mediated liver damage (37 ). Regarding lipid profile, the present data showed that D-glucose and hyperglycemia elevate cholesterol, triglyceride, lactate dehydrogenase, and decreased HDL. These changes were restored by honey, propolis, and their combination toward the control level. Honey reduces cholesterol levels because of its antioxidant content [ 38 ]. Conclusively, honey and propolis contain a high quantity of antioxidants and antioxidant activity; propolis has a higher antioxidant quantity and activity than honey. Honey and propolis have alpha-glucosidase and alpha-amylase inhibitory activity; honey showed higher inhibitory activity than propolis. This might help explain part of the mechanism of action of the hypoglycemic effect. Administration of D-glucose causes hyperglycemia and a significant elevation in serum creatinine, blood urea, liver enzymes, lipid parameters, LDH, HOMA-IR, and urine excretion of protein. Also, the administration of D-glucose causes a significant lowering in insulin level, QUIKI, HDL, and urine excretion of creatinine. It causes some pathological changes in the liver, pancreas, and kidney tissue after 10 weeks. These changes were alleviated by daily treatment with honey, propolis, or their combination that was started 7 weeks after administration of D-glucose. The mechanism of action is unknown, but it might be related to propolis and honey's antioxidant activity and their alpha-amylase and alpha-glucosidase inhibitory activity. The combination of honey and propolis might represent a natural therapeutic intervention in managing proteinuria, AKI, acute liver injury, and diabetic complications. Also, the combination can be used to decrease the incidence of diabetes. Further studies to explore the mechanism of action are fundamental and help to extract the most active ingredients. Material And Methods Propolis and honey samples and extract preparations Propolis and organic multi-floral honey samples were collected from hives installed in the Sefrou region, Morocco. The propolis sample was frozen at -20ºC and the organic honey was stored at 3 ºC throughout the experiment period. The raw propolis sample was macerated in 30 ml of ethanol (70%, v/v) under mechanical stirring for one week. The final extracts were filtered (Whatman, nº1), and the filtrate was concentrated in a rotary evaporator. Distilled water was added to prepare the chosen concentration (200 mg/kg b.wt and 100 mg/kg b.wt) [ 39 ]. Honey was dissolved in distilled water in order to prepare (1 g/kg b.wt and 2 g/kg b.wt ) for animals ‘feeding. Chemical Analysis Of Honey And Propolis Extracts Total carbohydrates Total carbohydrate content was determined using the phenol-sulfuric acid method described by Ferrira-Santos et al. [ 40 ]. Honey or propolis extract (50 µL) was mixed with 150 µL of sulfuric acid (96–98% v/v). Then, 30 µL of phenol reagent (5%) was added and the final solution was heated for 5 min at 90 ◦C. The absorbance was measured at 490 nm by microplate reader after cooling down at room temperature for 5 min. Glucose (10–600 mg/L) was used as a standard to achieve the calibration curve (R2 = 0.992). The total carbohydrate content was expressed as a milligram of glucose equivalents (GlcE) per gram of extract (mg GLcE/g). Soluble Protein Content The soluble protein content was analyzed using the Bradford assay with some modifications [ 41 ]. A sample of 20 µL of honey or propolis extract was mixed with 230 µL of Bradford dye reagent. The microplate was placed in the dark for 5 min and the absorbance was measured at a wavelength of 595 nm by a UV/V spectrophotometer (Synergy HT, BioTek Instruments, Inc., U.S.A.). Bovine albumin serum was used to perform the standard curve (33–1000 mg/L, R2 = 0.989) and the results were expressed as milligram of BSA equivalents per gram of extracts (mg BSA/g). Total Protein Content The total protein content of honey and propolis was estimated by quantification of total nitrogen after sample acid digestion using a Kjeldahl digestor (Tecator, FOSS, Denmark), applying the nitrogen conversion factor (N × 6.25) [ 41 ]. Total Phenolic Content The total phenolic content was determined by the method of Folin-Ciocalteu [ 42 ]. Briefly, 60 µL of Folin − Ciocalteu reagent and 15 µL of sodium carbonate solution (75 g/L) were added to 5 µL of honey or propolis hydro-ethanolic extract. The concentration of the produced coloration was measured at 700 nm by a UV/V spectrophotometer (Synergy HT, BioTek Instruments, Inc., U.S.A.) after incubating the mixture for 5 min at 60 ◦C. Gallic acid (0–500 mg/L) was used as a standard to achieve the calibration curve (R2 = 0.996) and the results were expressed in mg gallic acid equivalent (GAE) per gram of extracts (mg GAE/g). Total Flavonoids Content Total flavonoid content was determined [ 43 ]. One hundred microliters of honey or ethanolic extract of propolis were mixed with sodium nitrite (5%) and 150 µL of AlCl3 solution (10%). After 6 min, 200 µL of NaOH solution (1%) was added and the mixture was properly mixed and allowed to stand in the dark for 60 min. The absorbance was measured at 510 nm. Quercetin (2.6–142 mg/L) was used to perform the standard curve (R2 = 0.997) and the results were expressed in milligram of quercetin equivalent (QE) per gram of extracts (mg QE/g). Identification And Quantification Of Polyphenols Compounds By Uhplc-dad Honey and propolis samples were analyzed using a Shi-matzu Nexpera X2 UPLC chromatograph equipped with Diode Array Detector (DAD) (Shimadzu, SPD-M20A) following the method described by (Ferreira-Santos et al., 2019). Separation was performed on a reversed-phase Acquity UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 µm particle size; from Waters) and a pre-column of the same material at 40 ◦C. The flow rate was 0.4 mL/min. HPLC grade solvents water/formic acid 0.1% (A) and acetonitrile (B) were used. The elution gradient for solvent B was as follows: from 0.0 to 5.5 min eluent B at 5%, from 5.5 to 17 min linearly increasing from 5 to 60%, from 17.0 to 18.5 min a linearly increasing from 60 to 100%; the column was equilibrated at 5% from 18.5 to 30.0 min. Phenolic compounds were identified by comparing their UV spectra and retention times with that of corresponding standards. Quantification was carried out using calibration curves for each analyzed compound using concentrations between 250 and 2.5 mg/L. In all cases, the coefficient of linear correlation was R2 > 0.99. Compounds were quantified and identified at different wavelengths (209–370 nm). The values of individual phenolic compounds were expressed in milligrams per kilogram of samples (mg/Kg). All analyses were made in triplicate. Antioxidant Activity Of Honey And Propolis Extracts Total antioxidant activity The total antioxidant activity of honey or propolis samples was evaluated by the phosphomolybdenum method according to the method described by Prieto et al. [ 44 ] as follows: 1 ml of reagent solution (6 M sulfuric acid, 28 mM sodium phosphate, and 4 mM ammonium molybdate) was added to 25 µL of ethanolic extract of propolis or honey and the mixture was incubated for 90 min in a water bath at 95°C. The absorbance was read at 695 nm and ascorbic acid was used as the standard calibration (0.171 to 0.872 mg/mL, R2 = 0.999). The results were expressed in milligrams of ascorbic acid equivalent (AAE) per gram of the sample (mg AAE/g). Free radical scavenging activity (DPPH assay). Two hundred and seventy µL of 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) solution (150 µM, prepared in methanol with an absorbance of 0.700 ± 0.01 at 515 nm) was added to 30 µl of different dilutions of honey or propolis extracts [ 44 ]. Then, the mixture reactions were incubated in the dark for 1 h at room temperature. The absorbance was measured at 515 nm and the antiradical activity (% inhibition) was calculated using Eq. ( 1 ). DPPH inhibition concentration at 50% (IC 50 ) was determined using six different dilutions of each sample, considering that the percent inhibition had to be between 20% and 80%, and the results were expressed in micrograms of extracts per mL (mg/mL). $$\text{%} \text{i}\text{n}\text{h}\text{i}\text{b}\text{i}\text{t}\text{i}\text{o}\text{n}=\frac{\text{A}\text{b}\text{s} \text{c}\text{o}\text{n}\text{t}\text{r}\text{o}\text{l}-\text{A}\text{b}\text{s} \text{s}\text{a}\text{m}\text{p}\text{l}\text{e}}{\text{A}\text{b}\text{s} \text{c}\text{o}\text{n}\text{t}\text{r}\text{o}\text{l}} \times 100 \left(1\right)$$ Alpha-amylase Inhibitory Assay Five hundred µL of alpha-amylase solution (0.5 mg/mL) was incubated with 500 µL of different concentrations of honey or propolis extracts at 37 ◦C for 15 min. Afterward, 500 µL of starch solution (1%) was added and the mixture was incubated for 15 min at 37 ◦C. Immediately, 1 mL of dinitrosalicylic acid color reagent was added to the reaction and placed for 10 min in a boiling water bath. The final mixture was diluted 10 times and the absorbance of each dilution was read at 540 nm. Alpha-glucosidase Inhibitory Assay A mixture of different honey or propolis concentrations and p-nitrophenyl-R-d-glucopyranoside (pNPG, 3 mM) was added to the α-glucosidase solution (10U/mL). The mixture was incubated for 15 min at 37 ◦C, and the reaction was stopped by adding Na2CO3 solution (1 M). The intensity of p-nitrophenol coloration produced was measured at 400 nm. Alpha-amylase and alpha-glucosidase inhibition assays were determined as described previously by Laaroussi et al . [ 45 ]. Experimental Design Twenty-five male Wistar rats weighing 150.12 ± 5.1 grams, obtained from the Animal Housing Breeding Center, Department of Biology, Faculty of Sciences Dhar El Mahraz, University Sidi Mohamed Ben Abdallah, Fez, Morocco, were used for the experiments. Rats were kept in a ventilated room and lived in standard environmental conditions (22 ± 3°C, 55 ± 5% humidity, 12 h light/dark cycles). The present work was approved by IRB/ethics committee of Sidi Mohamed Ben Abdellah University, Fez ( USMBA-SNAMOPEQ 2017-03). The manipulation of animals respected the EU Directive 2010/63/EU for animal experiments to avoid and minimize animal suffering and the number of animals experimented. All methods were performed in accordance with the relevant guidelines and regulations. The study is reported in accordance with ARRIVE guidelines ( https://arriveguidelines.org ). For the first 7 weeks, groups 2, 3,4, and 5 received only D-glucose and had free access to tap water and normal rats’ chow diet. On the last day of the 7 weeks, rats in groups 3, 4, and 5 with fasting blood glucose greater than 9.4 mmol/L were treated with propolis, honey, and a mixture of honey and propolis respectively for the following 3 weeks. Rats were randomly allocated into 5 groups, 5 rats in each group. The treatments and applied procedures are as follows: Group 1 (control): received distal water (10 ml/kg b.wt) for 10 weeks. Group 2 (diabetic): received daily by gavage D-glucose (10 g/kg b.wt) for the first 7 weeks, Group 3 (diabetic + Propolis): received daily by gavage D-glucose (10 g/kg b.wt) for the first 7 weeks and treated with propolis extract (200mg/kg b.wt) for the following 3 weeks, Group 4 (diabetic + honey): received daily by gavage D-glucose (10 g/kg b.wt) for the first 7 weeks and treated with honey (2g/kg b.wt) for the following 3 weeks, Group 5 (diabetic, propolis, and honey): received daily by gavage D-glucose (10 g/kg b.wt) for the first 7 weeks and treated daily with 100mg/kg b.wt propolis extract + 1g/kg b.wt honey for the following 3 weeks. Blood samples, urine samples including 24-hour collection, and histopathological specimens were prepared at the end of 10 weeks. The treatment duration and honey and propolis extract doses were selected according to other studies [ 46 – 48 ]. Biochemical analysis Aspartate aminotransferases (AST), alanine aminotransferases (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), serum uric acid, serum creatinine, blood urea, total bilirubin, serum albumin, and serum protein were measured by enzymatic methods, using specific commercial reagent kits. All the kits were purchased from Bio-Maghreb Casablanca, Morocco. Urine and serum sodium, potassium, chloride, and phosphorus were analyzed using the ion-selective potentiometry method (Architect c8000i biochemistry analyzer), and calcium was determined based on its reaction with Arsenazo III (2,2′ -[1,8-Dihydroxy-3,6-disulphonaphthylene-2,7-bisazo]- bisbenzenear-sonic acid). The intensity of produced color was measured chromatically at 660/700 nm (Architect c8000i biochemistry analyzer). Blood glucose and plasma insulin levels were determined by the radioimmunoassay method (Rat insulin RIA kit, Millipore, St Charles, MO, USA). Model homeostasis evaluation (HOMA-IR) (Eq. ( 1 )), and homeostatic model-β (HOMA-β) were calculated following the formula described by Mattews et al . [ 49 ]. The quantitative insulin sensitivity check index (QUICKI) was determined according to Katz et al .[ 50 ]. $$HOMA-IR=\frac{Insulin \left(\frac{U}{L}\right) \times Glucose \left(\frac{mmol}{L}\right)}{22.5}$$ 1 $$\text{H}\text{O}\text{M}\text{A}-{\beta }=\frac{20 \times \text{I}\text{n}\text{s}\text{u}\text{l}\text{i}\text{n} \left(\frac{\text{U}}{\text{L}}\right)}{\text{G}\text{l}\text{u}\text{c}\text{o}\text{s}\text{e} \left(\frac{\text{m}\text{m}\text{o}\text{l}}{\text{L}}\right)}- 3.5 \left(2\right)$$ $$\text{Q}\text{U}\text{I}\text{C}\text{K}\text{I}=\frac{1}{(\text{log}\text{f}\text{a}\text{s}\text{t}\text{i}\text{n}\text{g} \text{i}\text{n}\text{s}\text{u}\text{l}\text{i}\text{n} \text{l}\text{e}\text{v}\text{e}\text{l} \left(\frac{{\mu }\text{U}}{\text{m}\text{l}}\right)+\text{log}\text{f}\text{a}\text{s}\text{t}\text{i}\text{n}\text{g} \text{b}\text{l}\text{o}\text{o}\text{d} \text{g}\text{l}\text{u}\text{c}\text{o}\text{s}\text{e} \left(\frac{\text{m}\text{g}}{\text{d}\text{l}}\right))}$$ 3 Liver, pancreas, and kidney antioxidant enzymes activities At the end of the experiment (10 weeks), the kidney, liver, and pancreas were quickly removed, placed in ice-cold saline solution and trimmed off adipose tissue then homogenized in cold phosphate-buffered saline (0.1 M; pH 7.4) and centrifuged (-4°C). The supernatant was collected and stored at -20°C for analysis of the oxidative parameters. Catalase (CAT) activity was calculated according to the method of Aebi [ 51 ]. A decrease in absorbance due to H 2 O 2 degradation was monitored spectrophotometrically at 240 nm for 1 min and the activity was expressed as µmolH 2 O 2 /min/mg protein. Glutathione peroxidase (GPx) activity was estimated according to the method of Wa [ 52 ]. The activity was expressed as moles of GSH oxidized/min/mg protein. Reduced glutathione ( GSH) levels were measured following the protocol described by Ellman [ 53 ]. Briefly, 3 mL of sulfosalicylic acid (4%) was added to 500 mL of homogenate tissues. The mixture was centrifuged at 2,500 g for 15 min and then prepared Ellman’s reagent was added to 500 mL of supernatant. The absorbance was measured at 412 nm after 10 min. Total GSH content was expressed as µg/gram of tissue. The formation of products of lipid peroxidation was quantified in liver and kidney tissues using the thiobarbituric acid-reactive substances (TBARS) method, as reported previously by Kassan et al. [ 54 ], The absorbance was measured at 532 nm. Results were expressed as malondialehyde (MDA) concentration (nmol/g tissue). Statistical analysis All data are presented as mean ± SD (standard deviation). Statistical comparisons between the groups were performed with one-way analysis of variance (ANOVA) followed by the Tukey test using GraphPad Prism® software (version 5.0; GraphPad Software, Inc., San Diego, USA). t-test was used to compare two means. Significance was accepted at p < 0.05 . Declarations Author contribution S.T., H.L., A.A., N.H., H.I., A.E., I.E., B.L. designed the experimental protocols and participated in the experimental work. S.T. wrote part of the paper. N.A. analyzed the data and results, wrote the main manuscript text, and submitted the manuscript for publication. 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Samples Carbohydrates (mg Glceq/g) Soluble Proteins (mg BSA/g) Total proteins (% ) TPC (mg GAE/g) TFC (mg QE/g) TAA (mg AAE/g) DPPH IC 50 (mg/mL) Propolis 1.57±0.02 22.18±2.11 2.32±0.02 65.22±3.73 25.98±5.81 79.12±7.04 0.34± 0.03 Honey 698.19±5.22a 3.42±0.01a 0.36±0.01a 28.54±1.04a 16.35±1.19a 68.72±6.51 1.11± 0.01a P value 0.001 0.001 0.001 0.001 0.048 0.112 0.001 a: significant compared to propolis. Table 2 . Phenolic compounds identification and quantification of propolis and honey using UPLC-DAD . Compounds (mg/kg) Propolis Honey p-value Aloine n.d 239.51± 5.1 Catechin 8.15±0.1 9.3 ± 2.0 0.376 Vanilic Acid 15.04±0.7 5.8 ± 0.2 a 0.001 o -Coumaric Acid n.d. 13.4 ± 0.7 Ferrulic Acid 56.78±0.6 17.1 ± 1.0a 0.001 Ellagic Acid 78.92±3.8 27.6 ± 0.3a 0.001 Naringin 213.76±0.5 11.8± 0.2 a 0.001 Hesperidin 121.98 ± 0.3 n.d Apigenin 50.37 ± 0.8 24.8 ± 0.2a 0.001 Cinnamic Acid 42.87±0.4 4.7 ± 0.3a 0.001 Resveratrol 81.22 ± 0.2 17.6 ± 3.7a 0.001 Rosmarinic Acid 105.09 ± 5.2 38.4± 4.1a 0.001 Rutin 60.11 ± 2.1 n.d Chlorogenic acid 11.19 ± 0.1 n.d Quercetin 22.51 ± 1.3 n.d Kaempferol 89.64 ± 1.2 14.9 ±2.8a 0.001 Gallic acid n.d. 18.8 ± 0.5 Values of phenolic compounds are expressed in concentration (mg/kg) [mean ± SD, 3 experiments] . n.d: not detected. a: significant compared to propolis. Table 3 : Alpha-amylase and alpha-glucosidase inhibitory activities of propolis and honey samples. Variables Alpha- amylase Alpha-glucosidase P value Honey 1394 ± 23.47 1083 ± 31.14a <0.001 Propolis 233 ± 8.97b 561 ± 27.13a,b <0.001 Acarbose 35.69 ± 1.29b,c 11003 ± 6.17a,b,c <0.001 P value <0.001 <0.001 a: significant compared to alpha-amylase activity. b: significant compared to honey. c: significant compared to propolis. Table 4: Effect of interventions on blood glucose, insulin, HOMA-IR, HOMA-B, and QUICKI. Parameters Interventions F/P value C D D+P D+H D+P+H Glucose (mmol/l) 5.33± 0.40 9.92 ± 0.52a 7.19 ± 0.16a,b 7.58 ± 0.28a,b 6.89 ± 0.55a,b, 82/0.001 Insulin (U/l) 11.71 ±0.60 25.22 ± 0.86a 16.19 ± 0.27a,b 21.42 ± 1.4a,b,c 14.01 ± 0.62a,b,c,d 216.6/0.001 HOMA-IR 2.78 ± 0.33 11.13 ± 0.86a 5.17 ± 0.20a,b 7.23 ± 0.75a,b,c 4.29 ± 0.36a,b,d 165/0.001 HOMA-B 40.55 ±2.31 47.41 ± 2.33a 41.51± 0.53,b 52.96 ± 2.27a,c 37.35 ± 3.86,b,d 33.1/0.001 QUICKI 0.16 ±0.001 0.15 ± 0.007a 0.15 ± 0.004a 0.15 ± 0.001a 0.15± 0.004a 6/0.002 H: Honey, P: Propolis, C: Control, D; D-glucose a: compared to C b: compared to D c: compared to D +P d: compared to D + H Table 5: Effect of interventions on liver function tests and lipid profile. Parameters Interventions F/P value C D D+P D+H D+P+H TC 46.71 ± 2.72 64.75 ± 2.30a 55.93 ± 2.33a,b 57.36 ± 3.13 54.5 ± 8.68 11/0.001 LDL 40.19 ± 3.50 48.69 ± 2.6a 44.62± 2.20 45.51 ±4.27 40.32± 4.45 5.4/0.003 HDL 19.73 ± 0.61 13.42 ±1.36a 16.3 ± 1.93 17 ± 2.19 16.68 ± 1.83 9/0.001 TG 27.68 ± 1.72 43.31 ± 2.82a 36.71 ± 3.65a 36.77 ±4.28 36.52± 3.53 13.7/0.001 ALT 68.13± 2.21 94 ±3.54a 80.2 ±2.95a,b 82.88 ± 2.58a 76.5± 2.23b 60.38/0.001 AST 144.4± 6.35 198 ±5.2a 170± 7.9b 175 ± 11.4a 160.9 ± 10.3b 28.31/0.001 ALP 52.8 ± 4.66 94.33 ± 13.3a 76.9 ± 4.47a 79.2 ± 8.33a 75.6 ±6.3a 17.85/0.001 LDH 59.9 ± 4.2 99.2 ± 10.35a 72.27 ± 8.2a,b 73 ± 4.3b 72 ± 4.9 22.18/0.001 TB 0.75 ± 0.04 1.32 ±0.07a 1.03 ± 0.04a,b 0.92 ± 0.03a,b 0.81b ±0.07 91.06/0.001 Albumin 4.39 ± 0.27 2.69 ±0.10a 3.64 ± 0.17 3.61 ± 0.27 3.76 ± 0.35 30/0.001 H: Honey, P: Propolis, C: Control, D; D-glucose a: compared to C b: compared to D c: compared to D +P d: compared to D + H Table 6 : Effect of interventions on kidney function tests. Parameters Interventions F/P value N D D+P D+H D+P+H Urea (mg/dl) 32.9 ± 4.87 74.5 ± 5.99a 52.9 ± 10.9a 52.8 ± 5.1a,b 47.4 ± 2.9b 25.3/0.001 Creatinine (mg/d) 0.64 ± 0.03 1.23 ± 0.03a 0.92 ±0.02a,b 0.97 ± 0.11a,b 0.81 ± 0.04a,b,c 74.2/0.001 Uric acid (mg/dl) 1.8 ± 0.07 2.55 ± 0.28a 2.0 ± 0.14b 2.11 ± 0.08 2.07 ± 0.06b 16.7/0.001 Urine creatinine(mg/ml) 53.4 ± 4.7 34.5 ± 4.4a 47.5 ± 4.5b 42.73 ± 8.2 47.8 ± 2.85b 8.84/0.001 Urine uric acid (mg/ml) 8.53 ± 0.34 12.34 ± 0.53a 9.83 ± 0.43b 10.23 ± 0.60 9.99 ± 0.57b 63.99/0.001 Urine protein (mg/ml) 27.3 ± 2.16 36.53± 1.9a 29.9 ±2.4b 32.27± 0.8b 30.3 ± 2.0b 15.94/0.001 H: Honey, P: Propolis, C: Control, D; D-glucose a: compared to C b: compared to D c: compared to D +P d: compared to D + H Table 7 : Effects of the interventions on blood and urine electrolytes. Electrolytes (mmol/l) Sodium Potassium Chloride Phosphorous Calcium Serum level C 145.85 ± 7.35 4.45 ± 0.05 105.00 ± 8.42 2.17 ± 0.01 2.82 ± 0.04 D 130.50 ± 5.12a 4.17 ± 0.09a 107.12 ± 5.64 2.01 ± 0.03a 2.75 ± 0.08 D+P 137.64 ± 5.23 4.48 ± 0.03b 104.50 ± 5.24 2.09 ± 0.01 2.81 ± 0.01 D+H 147.28 ± 6.38c 4.43±0.03b 113.00 ± 7.212 2.15 ± 0.05b 2.85 ± 0.01 D+P+H 141.12 ± 4.61 4.56± 0.07b,d 108.76 ± 6.34 2.13 ± 0.02b 2.82 ± 0.06 F/P value 6.99/0.001 30/0.001 1.46/0.25 25/0.001 2.81/0.052 Urinary level C 90.41 ± 4.37 60.84 ± 3.66 82.16 ± 3.85 1.28 ± 0.03 2.63 ± 0.05 D 110.58 ± 1.23a 60.91 ± 5.18 82.10± 7.25 1.26 ± 0.07 2.70 ± 0.11 D+P 88.34 ± 6.41b 60.85 ±4.54 80.14 ± 5.68 1.28 ± 0.02 2.67 ± 0.08 D+H 101.62 ± 7.73 60.82 ± 2.97 86.92± 5.11 1.27 ± 0.02 2.69 ± 0.06 D+P+H 97.13 ± 6.58 60.88 ± 3.82 83.17 ± 4.94 1.30 ± 0.05 2.61 ± 0.03 F/P value 12.1/0.001 0.06/0.992 1.122/0.374 0.60/0.664 1.47/0.248 H: Honey, P: Propolis, C: Control, D; D-glucose a: compared to C b: compared to D c: compared to D +P d: compared to D + H Table 8 : Effect of interventions on D-glucose-induced changes in antioxidant enzymes, proteins, and MDA concentrations in pancreatic tissues. Parameters/ pancreatic tissue Interventions F/P value C D D+P D+H D+P+H GSH (ug/g tissue) 33.1± 4.07 11.85 ± 0.28a 29.48 ± 6.5b 23.0 ± 6.5b 28 ± 2.94b 15.2/0.001 GPx (nmol GSH/min/mg prt) 12.66 ± 3 4.45 ± 0.35a 7.47 ± 1.17b 7.97 ± 2.1 8.37 ± 1.06b 13.76/0.001 MDA (nmol/g tissue) 28.84± 8.15 58.26 ± 8.97a 37.7 ± 4.87 31.73 ± 4.47b 33.17 ± 6.6b 12.11/0.001 CAT (µmol H2O2/min/mg prt) 20.54 ± 3 11.25 ± 1.47a 17.6 ± 1.66b 16.5 0.43b 18.49 ± 1.5b 20.6/0.001 Protein (mg/g tissue) 7 ± 0.35 5.48 ± 0.03a 5.75 ± 0.31a 5.27± 0.1a 6.5 ± 0.16 b,c,d 53.6/0.001 H: Honey, P: Propolis, C: Control, D; D-glucose a: compared to C b: compared to D c: compared to D +P d: compared to D + H Table 9 : Effect of interventions on D-glucose-induced changes in antioxidant enzymes, proteins, and MDA concentrations in liver tissues. Parameters/ liver tissue Interventions F/P value C D D+P D+H D+P+H GSH (ug/g tissue) 16.0 ±1.15 12.36± 2.98 15.2 ± 2.29 15.48 ± 1.56 15.66 ± 2.07 2.56/0.65 GPx (nmol GSH/min/mg prt) 10.38 ± 0.75 5.56 ±0.27a 8.18 ± 0.2b 9.81 ± 1.2b 11.96 ± 2.33b 7.18/0.001 MDA (nmol/g tissue) 40.58 ± 11.2 70.2 ± 12a 49.87 ± 12.6 46.87 ± 5b 47.6 ± 6.11 6.56/0.001 CAT (µmol H2O2/min/mg prt) 27.28± 5.2 14.6 ± 2.1a 20.85 ± 3.3 30.3 ± 6.32b 23.9 ± 2.22b 11.49/0.001 Protein (mg/g tissue) 6.4 ± 0.15 4.44 ± 0.21a 5.1 ± 0.17a,b 5.33± 0.17a,b 5.2± 0.5a,b 34/0.001 H: Honey, P: Propolis, C: Control, D; D-glucose a: compared to C b: compared to D c: compared to D +P d: compared to D + H Table 10 : Effect of interventions on D-glucose induced changes in antioxidant enzymes, proteins, and MDA concentrations in kidney tissues. Parameters/ Kidney tissue Interventions F/P value C D D+P D+H D+P+H GSH (ug/g tissue) 21 ± 1.55 9.6 ± 2.4a 16.6 ± 0.14a,b 16.1 ± 2.56 16.9 ± 1.42b 25.5/0.001 GPx (nmol GSH/min/mg prt) 14.4 ± 1.9 8 ± 1.4a 12.8 ± 2.22 11.12 ± 1.02 12.8 ± 1.4b 11.03/0.001 MDA (nmol/g tissue) 31.7 ± 3.7 47.3 ± 3.3a 43.3 ± 4.0a 35.3 ± 7.1 37.5 ± 4.2 9.5/0.001 CAT (µmol H2O2/min/mg prt) 19.4 ± 1.3 12.9 ± 0.78 a 16.6 ± 1.86b 15.4 ± 0.7a 16.28 ± 2.4a,b 10.6/0.001 Protein (mg/g tissue) 5.1 ±0.54 3.4 ± 0.19a 4.1± 0.7 4.56 ± 0.29b 4.33 ± 0.41 8.34/0.001 H: Honey, P: Propolis, C: Control, D; D-glucose a: compared to C b: compared to D c: compared to D +P d: compared to D + H Table 11 : level of oxidant and anti0xidants in the liver, pancreas, and kidney tissues in the control group. Parameters Organs F/P Liver Pancreas Kidney GSH (ug/g tissue) 16.86 ± 1.15 33.1 ± 4.07a 21± 1.55b 58.8/0.001 GPx (nmol GSH/min/mg prt) 10.38 ± 0.75 12.66± 3.2 14.4 ± 1.9 4.58/0.333 MDA (nmol/g tissue) 40.58 ± 11 28.84 ± 8.15 31.7 ± 4 2.45/0.127 CAT (µmol H2O2/min/mg prt) 27.28 ± 5.2 20.54 ± 3 19.4 ± 1.3a 7.5/0.007 Protein (mg/g tissue) 6.4 ±0.15 7 ± 0.35 5 ± 0.54 a,b 40/0.001 a: compared to liver. b: compared to the pancreas. 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. 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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-2697406","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":187605063,"identity":"114a3984-de7b-432b-a001-c97d37e0b81a","order_by":0,"name":"Soumaya Touzani","email":"","orcid":"","institution":"University Sidi Mohamed Ben Abdellah","correspondingAuthor":false,"prefix":"","firstName":"Soumaya","middleName":"","lastName":"Touzani","suffix":""},{"id":187605064,"identity":"9e35eabe-2461-4358-807b-7b5ab80adc72","order_by":1,"name":"Noori Al-Waili","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYLCCxH82cvwMDGwkaElgSzOWbCBJCwPb4USDA8RqMWdvPvbhAU9agvGN5GcPPlQwyPOLHcCvxbLnWPKMBAmbPLMbaeaGM84wGM6cnYBfi8GNHGOGBIO0YrMbCWbSvG1A9m2itCQcTtw8I/0bKVoOHE7cIJFDrC1njiUzJDakGUuceVMmOeOMBBF+Od58mPFnAzAq29O3SXyosJHnlyagBQEEwColiFUOAvwHSFE9CkbBKBgFIwkAABi3QmnQEeo1AAAAAElFTkSuQmCC","orcid":"","institution":"New York Medical care for Nephrology","correspondingAuthor":true,"prefix":"","firstName":"Noori","middleName":"","lastName":"Al-Waili","suffix":""},{"id":187605067,"identity":"de4dd0e3-0b0a-41e4-8906-e688d6751626","order_by":2,"name":"Hassan Laaroussi","email":"","orcid":"","institution":"University Sidi Mohamed Ben Abdellah","correspondingAuthor":false,"prefix":"","firstName":"Hassan","middleName":"","lastName":"Laaroussi","suffix":""},{"id":187605068,"identity":"b1e8f0de-86ac-4c49-b42f-4dc0277245a1","order_by":3,"name":"Abderrazak Aboulghazi","email":"","orcid":"","institution":"University Sidi Mohamed Ben Abdellah","correspondingAuthor":false,"prefix":"","firstName":"Abderrazak","middleName":"","lastName":"Aboulghazi","suffix":""},{"id":187605070,"identity":"34f9cd0e-208d-44aa-abed-08420a679f6c","order_by":4,"name":"Nawal Hamas","email":"","orcid":"","institution":"University Hospital Hassan II","correspondingAuthor":false,"prefix":"","firstName":"Nawal","middleName":"","lastName":"Hamas","suffix":""},{"id":187605071,"identity":"2c5c9a93-6e7e-4f4b-a664-88c49445c5a6","order_by":5,"name":"Hamada Imtara","email":"","orcid":"","institution":"Arab American University","correspondingAuthor":false,"prefix":"","firstName":"Hamada","middleName":"","lastName":"Imtara","suffix":""},{"id":187605073,"identity":"1022d0c0-75da-45cb-9b38-d4bf1a4a3088","order_by":6,"name":"Asmae ElGouizi","email":"","orcid":"","institution":"University Sidi Mohamed Ben Abdellah","correspondingAuthor":false,"prefix":"","firstName":"Asmae","middleName":"","lastName":"ElGouizi","suffix":""},{"id":187605074,"identity":"9f46cda0-1cdb-4016-82e0-111a985d52c4","order_by":7,"name":"Ilham ElArabi","email":"","orcid":"","institution":"University Sidi Mohamed Ben Abdellah","correspondingAuthor":false,"prefix":"","firstName":"Ilham","middleName":"","lastName":"ElArabi","suffix":""},{"id":187605075,"identity":"84055cad-3696-489d-aa39-8ae962fc912c","order_by":8,"name":"Ahmed Al-Waili","email":"","orcid":"","institution":"New York Medical care for Nephrology","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"","lastName":"Al-Waili","suffix":""},{"id":187605076,"identity":"659e7a5c-07c1-4eaa-8737-eb600b1dc93d","order_by":9,"name":"Badiaa Lyoussi","email":"","orcid":"","institution":"University Sidi Mohamed Ben Abdellah","correspondingAuthor":false,"prefix":"","firstName":"Badiaa","middleName":"","lastName":"Lyoussi","suffix":""}],"badges":[],"createdAt":"2023-03-15 16:59:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2697406/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2697406/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":35107305,"identity":"1d232b4a-e2e6-48c1-80fb-8ac7e1281fbc","added_by":"auto","created_at":"2023-03-31 14:47:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1088912,"visible":true,"origin":"","legend":"\u003cp\u003eKidney\u003c/p\u003e\n\u003cp\u003eDG: D-glucose\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eControl: \u003c/strong\u003eno\u003cstrong\u003e \u003c/strong\u003evascular\u003cstrong\u003e \u003c/strong\u003econgestion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDG+Honey:\u003c/strong\u003e mild vascular congestion\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDG+Propolis: \u003c/strong\u003emild\u003cstrong\u003e \u003c/strong\u003evascular congestion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDG+H+P:\u003c/strong\u003e mild vascular congestion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDG\u003c/strong\u003e: vascular congestion + hemorrhagic foci in the kidneys.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-2697406/v1/f1d80aac1aec5993f5e6a36d.png"},{"id":35107304,"identity":"df29bbef-b012-43b1-b19f-d5b21bee9753","added_by":"auto","created_at":"2023-03-31 14:47:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":373048,"visible":true,"origin":"","legend":"\u003cp\u003eLiver\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-2697406/v1/928cf90d513d61cae0207ab7.png"},{"id":35107306,"identity":"bedad6d0-b27b-4ef8-a234-4db4a25bb48e","added_by":"auto","created_at":"2023-03-31 14:47:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":398289,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePancreas\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-2697406/v1/49e45bc0431c2b7f03fc37f8.png"},{"id":37270182,"identity":"45e04c9e-ea11-4c25-b3ce-39f9bdc743ae","added_by":"auto","created_at":"2023-05-20 08:44:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3004812,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2697406/v1/19ccb659-e6c4-430e-ba31-b0494fbfb29b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The effect of propolis and honey on oxidant and antioxidant parameters and D-glucose induced hyperglycemia, acute kidney injury and proteinuria in rats","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHoney and propolis are bee natural products that showed various biological and therapeutic activities in pre-clinical and clinical studies conducted in animals and humans. Honey ameliorates diabetic nephropathy caused by streptozotocin [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].]. It prevents hyperglycemia and ameliorates renal and hepatic injury in diabetic mice [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In addition to its hypoglycemic effect, honey prevents dyslipidemia and histopathological changes in pancreatic islets in diabetic rats [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. It was proposed that honey content of antioxidants, zinc, copper, and selenium might play a role in honey`s hypoglycemic effect [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRegarding kidney function, honey protects renal and hepatic injuries and increases urine volume in lead and CCl4 intoxication [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Honey demonstrated diuretic, natriuretic and kaliuretic activity [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Induction of diabetes in rats increased oxidative stress and decreased antioxidants in the kidneys tissue which were attenuated with the use of honey [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. A recent study showed that honey in doses of 1,2 and 3 grams /kg b.wt for 16 weeks ameliorates renal dysfunction, metabolic acidosis, and renal histological changes in high fructose diet-fed Wistar rats \u003cb\u003e[ 11\u003c/b\u003e]. In a clinical study, honey has a beneficial effect on kidney function and inflammatory mediators [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHoney has been mentioned in the Holy books, the Talmud, both the old and new testaments of the Bible, and the Holy Quran as a healer of diseases. In the Surat Al-Nahel (The Bee) it says: \u003cem\u003eAnd the LORD taught the bee to build its cells in mountains, on tree, and in men\u0026rsquo;s habitations, then to eat of all the fruits of the earth and find with skill the spacious paths of its LORD, there issues from within their bodies a drink of varying colors, wherein is healing for men, verily in this is a sign for those who give thought\u003c/em\u003e.\u003c/p\u003e \u003cp\u003eData showed that propolis has antioxidant and renal and hepatic protective activities [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In earlier observations, propolis demonstrated higher antioxidant activity than honey [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In diabetic rats, propolis significantly improves blood glucose levels, increases insulin sensitivity, and decreases oxidative stress in diabetic rats [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Propolis has an anti-advanced glycation end-products activity [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Interestingly, we found that propolis decreases urinary protein excretion and prevents acute kidney and liver injuries caused by ethylene glycol ingestion in rats [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePropolis and honey are great candidates to be used in the management of diabetes, and their combination might have a synergistic or additive effect [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Therefore, the present study evaluated honey and propolis's effect and their combination collected from Moroccan areas on blood glucose and insulin level, acute kidney injury (AKI), liver injury, proteinuria, and lipid parameters in D-glucose-induced diabetic rats. The investigations included studying physicochemical characteristics, antioxidant content, and antioxidant activity of propolis and honey samples.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e showed that propolis has significantly higher total protein and antioxidant activity than honey while carbohydrate is higher in honey than in propolis (p\u0026lt;0.05). The honey sample contains fructose\u0026nbsp;34,22 \u0026plusmn; 1,92 g/100g, glucose 23.34 \u0026plusmn; 2.52 g/100 g, maltose and sucrose 2.11 \u0026plusmn; 0.07 g/100g, and HMF 9.729.72\u0026plusmn;0.11. Furfural was not detected.\u003c/p\u003e\n\u003cp\u003eRegarding phenolic compounds, \u003cstrong\u003etable 2\u003c/strong\u003e demonstrated various phenolic compounds in both honey and propolis. Compared to honey, propolis has higher concentrations of vanillic acid, naringin, hesperidin, quercetin, rutin, and kaempferol,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e showed that honey has higher alpha-amylase inhibitory activity than propolis and acarbose and higher alpha-glucosidase inhibitory activity than propolis (P\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEffect of interventions on blood glucose, insulin, HOMA-IR, HOMA-B, and QUICKI\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eD-glucose caused a significant elevation of blood glucose, insulin, HOMA-B, and HOMA-IR (\u003cstrong\u003eTable 4\u003c/strong\u003e). The use of propolis, honey, and a combination of propolis and honey with D-glucose decreased these parameters toward the control levels (P\u0026lt;0.05). The combined use of propolis and honey with D-glucose showed a significantly stronger effect than the use of propolis with D-glucose or honey with D-glucose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEffect of interventions on liver function tests and lipid profile\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5\u003c/strong\u003e showed that D-glucose increases total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein (LDL), and decreases high-density lipoprotein (HDL), these changes markedly improved with the use of propolis, honey, and their combination with D-glucose; the use of hone and propolis with D-glucose showed a stronger effect compared to propolis or honey (p\u0026lt;0.05). D-glucose increased liver enzymes, TB, and decreased albumin level (p\u0026lt;0.05). The combined use of honey, propolis, or their combination with D-glucose significantly improved these changes toward the control values. The use of both honey and propolis in rats treated with D-glucose showed a stronger effect than the effects seen with the use of propolis or honey (p\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEffect of interventions on AKI induced by D-glucose and blood and urine electrolytes.\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eD-glucose increased blood urea, serum creatinine, serum uric acid, urine protein, and urine uric acid (\u003cstrong\u003eTable 6\u003c/strong\u003e). The use of propolis or honey in rats receiving D-glucose significantly ameliorates the effect of D-glucose on renal function tests by decreasing urine protein, blood urea, and serum creatinine. The use of a combination of propolis and honey demonstrated a stronger effect than propolis or honey individually (P\u0026lt;0.05). \u0026nbsp;\u003cstrong\u003eTable 7\u003c/strong\u003e demonstrated that D-glucose causes a significant lowering of serum sodium and potassium that was ameliorated with the use of propolis, honey, or their combination.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEffects of the interventions on antioxidant parameters, protein, and MDA levels in pancreatic, liver, and kidney tissues\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eD-glucose caused a significant decrease in glutathione (GHS), glutathione peroxidase (GPx), catalase (CAT), and protein and an increase in malondialdehyde (MDA) levels in pancreatic, liver, and kidney tissues,\u0026nbsp;\u003cem\u003eP\u0026lt;0.05\u003c/em\u003e (\u003cstrong\u003eTables 8-10\u003c/strong\u003e). The use of propolis, honey, or their combination significantly ameliorated D-glucose effects by increasing antioxidant parameters and protein and decreasing MDA levels. Table 11 showed the quantity of oxidants and antioxidants in the kidney, liver, and pancreatic tissues. \u0026nbsp; Pancreas tissue contains a higher amount of GHS than the liver and kidney and the liver tissue contains a higher amount of MDA than other tissues.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eHistological changes caused by the interventions.\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFigures 1,2 and 3 demonstrated some of the changes caused by d-glucose with and without the use of honey, propolis, or a combination of honey and propolis. It seems that honey and propolis alleviate the effects of D-glucose on the histopathological changes in the liver, kidney, and pancreatic tissues.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe data showed that treatment with honey, propolis, and their combination significantly alleviated the adverse effect of D-glucose-induced hyperglycemia on blood glucose and insulin level, and acute kidney and liver injuries. Honey and propolis decreased hyperglycemia, reduced insulin blood level, ameliorated AKI, proteinuria, and the elevation of hepatic enzymes. The interventions prevented crossly histological changes in the renal, hepatic, and pancreatic tissues after the induction of hyperglycemia in rats. Interestingly, the combination of honey and propolis was more potent than the effect of honey or propolis individually.\u003c/p\u003e \u003cp\u003eThe data from the chemical analysis demonstrated the presence of phenols and flavonoids in honey and propolis samples which possess a strong antioxidant capacity. Propolis contains a high amount of protein while honey contains a high amount of carbohydrates. Honey explores a higher alpha-amylase and alpha-glucosidase inhibitory activity than propolis. IC50 in the DPPH test was higher in propolis compared to honey and total antioxidant activity was higher in propolis compared to honey, which indicated higher antioxidant capacity in propolis compared to honey.\u003c/p\u003e \u003cp\u003eThe total phenol content of 17 various Moroccan honey samples including \u003cem\u003eArbutus unedo\u003c/em\u003e honey ranges between 16.38 mg GAE/100g (citrus honey) to 92.37 mg GAE/100 (thyme honey) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Therefore, the phenolic content in the multiflora honey sample collected from hives installed in the Sefrou region, Morocco (28.54\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04 mg GAE/g) is higher than the other Moroccan honey samples. The content of multiflora honey tested in the present study is higher than Manuka honey`s phenolic content (71 mg GAE/100g) and Iranian honey\u0026rsquo;s phenolic content (193.8 mg GAE/100g honey) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The data showed that multiflora honey from Sefrou region did not contain epicatechin which is rarely found in honey samples. However, our earlier study showed that \u003cem\u003ethyme vulgaris\u003c/em\u003e honey and \u003cem\u003eArbutus undeo\u003c/em\u003e honey collected from Morocco contain epicatechin [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The physicochemical characterization and the antioxidant content of honey samples vary, and the presented result showed that \u003cem\u003emultiflora\u003c/em\u003e honey's analyzed parameters were following the requirements of the International Honey Commission 2009 and codex standard for honey [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePropolis contains different types of phenolic acids, and 14 compounds were identified using UPLC/DAD. All the compounds detected were phenolic acids and their ester derivatives. The results showed that naringin, hesperidin, rosmarinic acid, and kaempferol were the most abundant in the propolis samples test in the present study. The analysis conducted in another propolis sample from Morocco revealed that pinobanksin-3-\u003cem\u003eO\u003c/em\u003e-acetate, pinocembrin, and caffeic acid phenylethyl ester were the most abundant phenolics [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The results of the DPPH test demonstrated that propolis showed a higher scavenging capacity against DPPH than honey.\u003c/p\u003e \u003cp\u003eAdministration of D- glucose caused diabetes with an elevation of blood glucose and insulin levels. It did not cause much change in pancreatic tissue such as a decrease in the islets of Langerhans. The administration of honey and propolis after induction of diabetes markedly restores hyperglycemia and hyperinsulinemia toward the normal range. D-glucose significantly increased HOMA-IR and decreased QUIKI. Therefore, D-glucose increased blood glucose level by increasing insulin resistance and decreasing insulin sensitivity. These changes were less evident with the use of honey and propolis because of decreasing insulin levels and HOMA-IR.\u003c/p\u003e \u003cp\u003eIn clinical settings, it was found that honey can reduce hyperglycemia and insulin resistance in diabetic patients [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The antioxidant ameliorates oxidative stress in the pancreatic tissues and stimulates insulin secretion [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Honey contains antioxidants and fructose which might be responsible for the hypoglycemic effect [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eComplex carbohydrates are hydrolyzed by pancreatic alpha-amylase and alpha-glucosidase enzymes, resulting in the production of glucose which is absorbed by the intestine. In our study, honey and propolis have alpha-glucosidase and alpha-amylase inhibitory activity; honey has higher inhibitory activity than propolis. Honey and propolis contain flavonoids that have alpha-amylase and glucosidase inhibitory activity (\u003cb\u003e29\u003c/b\u003e). Other studies confirm that honey and flavonoids possess significant alpha-amylase and alpha-glucosidase inhibitory activity [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. These findings might help explain the beneficial effect of honey and propolis on diabetes and might help in the prevention of diabetes Mellitus.\u003c/p\u003e \u003cp\u003eProteinuria and kidney diseases are common complications of diabetes. Acute hyperglycemia could cause AKI and oxidative stress [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. D-glucose administration and hyperglycemia caused AKI, proteinuria, an increase in urine uric acid, and a considerable decrease in the urinary excretion of creatinine. AKI was evident by a significant elevation of serum creatinine and blood urea. Interestingly, the use of honey or propolis significantly ameliorated AKI and proteinuria, and the combination of both showed a better effect.\u003c/p\u003e \u003cp\u003eThe data showed that honey, propolis, and their combination alleviate hyperglycemia-induced AKI. We have found that propolis prevents proteinuria, crystalluria, and AKI caused by ethylene glycol ingestion in rats [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Furthermore, propolis has higher antioxidant activity than honey [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Other studies showed phenols and flavonoids improving AKI, renal fibrosis, and inflammation [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Therefore, such findings might partly explore honey and propolis protective effect mechanisms of action against hyperglycemia-induced AKI and proteinuria.\u003c/p\u003e \u003cp\u003eHyperglycemia in rats causes liver toxicity and elevation of liver enzymes level [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The present result showed that hyperglycemia induced by D-glucose causes acute liver injury; there was a significant evaluation of liver enzymes and total bilirubin associated with a decrease in serum albumin level. We found similar results in streptozotocin-induced hyperglycemia [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Interestingly, the use of propolis and honey prevented liver injury. The protective effects might be related to high levels of antioxidants in honey and propolis. Hyperglycemia reduces the levels of antioxidants, increases levels of oxidants, and causes oxidation-mediated liver damage \u003cb\u003e(37\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eRegarding lipid profile, the present data showed that D-glucose and hyperglycemia elevate cholesterol, triglyceride, lactate dehydrogenase, and decreased HDL. These changes were restored by honey, propolis, and their combination toward the control level. Honey reduces cholesterol levels because of its antioxidant content [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConclusively, honey and propolis contain a high quantity of antioxidants and antioxidant activity; propolis has a higher antioxidant quantity and activity than honey. Honey and propolis have alpha-glucosidase and alpha-amylase inhibitory activity; honey showed higher inhibitory activity than propolis. This might help explain part of the mechanism of action of the hypoglycemic effect. Administration of D-glucose causes hyperglycemia and a significant elevation in serum creatinine, blood urea, liver enzymes, lipid parameters, LDH, HOMA-IR, and urine excretion of protein. Also, the administration of D-glucose causes a significant lowering in insulin level, QUIKI, HDL, and urine excretion of creatinine. It causes some pathological changes in the liver, pancreas, and kidney tissue after 10 weeks. These changes were alleviated by daily treatment with honey, propolis, or their combination that was started 7 weeks after administration of D-glucose. The mechanism of action is unknown, but it might be related to propolis and honey's antioxidant activity and their alpha-amylase and alpha-glucosidase inhibitory activity. The combination of honey and propolis might represent a natural therapeutic intervention in managing proteinuria, AKI, acute liver injury, and diabetic complications. Also, the combination can be used to decrease the incidence of diabetes. Further studies to explore the mechanism of action are fundamental and help to extract the most active ingredients.\u003c/p\u003e"},{"header":"Material And Methods","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePropolis and honey samples and extract preparations\u003c/h2\u003e \u003cp\u003ePropolis and organic multi-floral honey samples were collected from hives installed in the Sefrou region, Morocco. The propolis sample was frozen at -20\u0026ordm;C and the organic honey was stored at 3 \u0026ordm;C throughout the experiment period. The raw propolis sample was macerated in 30 ml of ethanol (70%, v/v) under mechanical stirring for one week. The final extracts were filtered (Whatman, n\u0026ordm;1), and the filtrate was concentrated in a rotary evaporator. Distilled water was added to prepare the chosen concentration (200 mg/kg b.wt and 100 mg/kg b.wt) [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Honey was dissolved in distilled water in order to prepare (1 g/kg b.wt and 2 g/kg b.wt ) for animals \u0026lsquo;feeding.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eChemical Analysis Of Honey And Propolis Extracts\u003c/h3\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eTotal carbohydrates\u003c/h2\u003e \u003cp\u003eTotal carbohydrate content was determined using the phenol-sulfuric acid method described by Ferrira-Santos et al. [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Honey or propolis extract (50 \u0026micro;L) was mixed with 150 \u0026micro;L of sulfuric acid (96\u0026ndash;98% v/v). Then, 30 \u0026micro;L of phenol reagent (5%) was added and the final solution was heated for 5 min at 90 ◦C. The absorbance was measured at 490 nm by microplate reader after cooling down at room temperature for 5 min. Glucose (10\u0026ndash;600 mg/L) was used as a standard to achieve the calibration curve (R2\u0026thinsp;=\u0026thinsp;0.992). The total carbohydrate content was expressed as a milligram of glucose equivalents (GlcE) per gram of extract (mg GLcE/g).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSoluble Protein Content\u003c/h3\u003e\n\u003cp\u003eThe soluble protein content was analyzed using the Bradford assay with some modifications [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. A sample of 20 \u0026micro;L of honey or propolis extract was mixed with 230 \u0026micro;L of Bradford dye reagent. The microplate was placed in the dark for 5 min and the absorbance was measured at a wavelength of 595 nm by a UV/V spectrophotometer (Synergy HT, BioTek Instruments, Inc., U.S.A.). Bovine albumin serum was used to perform the standard curve (33\u0026ndash;1000 mg/L, R2\u0026thinsp;=\u0026thinsp;0.989) and the results were expressed as milligram of BSA equivalents per gram of extracts (mg BSA/g).\u003c/p\u003e\n\u003ch3\u003eTotal Protein Content\u003c/h3\u003e\n\u003cp\u003eThe total protein content of honey and propolis was estimated by quantification of total nitrogen after sample acid digestion using a Kjeldahl digestor (Tecator, FOSS, Denmark), applying the nitrogen conversion factor (N \u0026times; 6.25) [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eTotal Phenolic Content\u003c/h3\u003e\n\u003cp\u003eThe total phenolic content was determined by the method of Folin-Ciocalteu [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Briefly, 60 \u0026micro;L of Folin\u0026thinsp;\u0026minus;\u0026thinsp;Ciocalteu reagent and 15 \u0026micro;L of sodium carbonate solution (75 g/L) were added to 5 \u0026micro;L of honey or propolis hydro-ethanolic extract. The concentration of the produced coloration was measured at 700 nm by a UV/V spectrophotometer (Synergy HT, BioTek Instruments, Inc., U.S.A.) after incubating the mixture for 5 min at 60 ◦C. Gallic acid (0\u0026ndash;500 mg/L) was used as a standard to achieve the calibration curve (R2\u0026thinsp;=\u0026thinsp;0.996) and the results were expressed in mg gallic acid equivalent (GAE) per gram of extracts (mg GAE/g).\u003c/p\u003e\n\u003ch3\u003eTotal Flavonoids Content\u003c/h3\u003e\n\u003cp\u003eTotal flavonoid content was determined [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. One hundred microliters of honey or ethanolic extract of propolis were mixed with sodium nitrite (5%) and 150 \u0026micro;L of AlCl3 solution (10%). After 6 min, 200 \u0026micro;L of NaOH solution (1%) was added and the mixture was properly mixed and allowed to stand in the dark for 60 min. The absorbance was measured at 510 nm. Quercetin (2.6\u0026ndash;142 mg/L) was used to perform the standard curve (R2\u0026thinsp;=\u0026thinsp;0.997) and the results were expressed in milligram of quercetin equivalent (QE) per gram of extracts (mg QE/g).\u003c/p\u003e\n\u003ch3\u003eIdentification And Quantification Of Polyphenols Compounds By Uhplc-dad\u003c/h3\u003e\n\u003cp\u003eHoney and propolis samples were analyzed using a Shi-matzu Nexpera X2 UPLC chromatograph equipped with Diode Array Detector (DAD) (Shimadzu, SPD-M20A) following the method described by (Ferreira-Santos et al., 2019). Separation was performed on a reversed-phase Acquity UPLC BEH C18 column (2.1 mm \u0026times; 100 mm, 1.7 \u0026micro;m particle size; from Waters) and a pre-column of the same material at 40 ◦C. The flow rate was 0.4 mL/min. HPLC grade solvents water/formic acid 0.1% (A) and acetonitrile (B) were used. The elution gradient for solvent B was as follows: from 0.0 to 5.5 min eluent B at 5%, from 5.5 to 17 min linearly increasing from 5 to 60%, from 17.0 to 18.5 min a linearly increasing from 60 to 100%; the column was equilibrated at 5% from 18.5 to 30.0 min. Phenolic compounds were identified by comparing their UV spectra and retention times with that of corresponding standards. Quantification was carried out using calibration curves for each analyzed compound using concentrations between 250 and 2.5 mg/L. In all cases, the coefficient of linear correlation was R2\u0026thinsp;\u0026gt;\u0026thinsp;0.99. Compounds were quantified and identified at different wavelengths (209\u0026ndash;370 nm). The values of individual phenolic compounds were expressed in milligrams per kilogram of samples (mg/Kg). All analyses were made in triplicate.\u003c/p\u003e\n\u003ch3\u003eAntioxidant Activity Of Honey And Propolis Extracts\u003c/h3\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eTotal antioxidant activity\u003c/h2\u003e \u003cp\u003eThe total antioxidant activity of honey or propolis samples was evaluated by the phosphomolybdenum method according to the method described by Prieto \u003cem\u003eet al.\u003c/em\u003e [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e] as follows: 1 ml of reagent solution (6 M sulfuric acid, 28 mM sodium phosphate, and 4 mM ammonium molybdate) was added to 25 \u0026micro;L of ethanolic extract of propolis or honey and the mixture was incubated for 90 min in a water bath at 95\u0026deg;C. The absorbance was read at 695 nm and ascorbic acid was used as the standard calibration (0.171 to 0.872 mg/mL, R2\u0026thinsp;=\u0026thinsp;0.999). The results were expressed in milligrams of ascorbic acid equivalent (AAE) per gram of the sample (mg AAE/g).\u003c/p\u003e \u003cp\u003e \u003cb\u003eFree radical scavenging activity (DPPH assay).\u003c/b\u003e \u003c/p\u003e \u003cp\u003eTwo hundred and seventy \u0026micro;L of 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) solution (150 \u0026micro;M, prepared in methanol with an absorbance of 0.700\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 at 515 nm) was added to 30 \u0026micro;l of different dilutions of honey or propolis extracts [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Then, the mixture reactions were incubated in the dark for 1 h at room temperature. The absorbance was measured at 515 nm and the antiradical activity (% inhibition) was calculated using Eq.\u0026nbsp;(\u003cspan refid=\"Equ1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). DPPH inhibition concentration at 50% (IC\u003csub\u003e50\u003c/sub\u003e) was determined using six different dilutions of each sample, considering that the percent inhibition had to be between 20% and 80%, and the results were expressed in micrograms of extracts per mL (mg/mL).\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\text{%} \\text{i}\\text{n}\\text{h}\\text{i}\\text{b}\\text{i}\\text{t}\\text{i}\\text{o}\\text{n}=\\frac{\\text{A}\\text{b}\\text{s} \\text{c}\\text{o}\\text{n}\\text{t}\\text{r}\\text{o}\\text{l}-\\text{A}\\text{b}\\text{s} \\text{s}\\text{a}\\text{m}\\text{p}\\text{l}\\text{e}}{\\text{A}\\text{b}\\text{s} \\text{c}\\text{o}\\text{n}\\text{t}\\text{r}\\text{o}\\text{l}} \\times 100 \\left(1\\right)$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAlpha-amylase Inhibitory Assay\u003c/h3\u003e\n\u003cp\u003eFive hundred \u0026micro;L of alpha-amylase solution (0.5 mg/mL) was incubated with 500 \u0026micro;L of different concentrations of honey or propolis extracts at 37 ◦C for 15 min. Afterward, 500 \u0026micro;L of starch solution (1%) was added and the mixture was incubated for 15 min at 37 ◦C. Immediately, 1 mL of dinitrosalicylic acid color reagent was added to the reaction and placed for 10 min in a boiling water bath. The final mixture was diluted 10 times and the absorbance of each dilution was read at 540 nm.\u003c/p\u003e\n\u003ch3\u003eAlpha-glucosidase Inhibitory Assay\u003c/h3\u003e\n\u003cp\u003eA mixture of different honey or propolis concentrations and p-nitrophenyl-R-d-glucopyranoside (pNPG, 3 mM) was added to the α-glucosidase solution (10U/mL). The mixture was incubated for 15 min at 37 ◦C, and the reaction was stopped by adding Na2CO3 solution (1 M). The intensity of p-nitrophenol coloration produced was measured at 400 nm. Alpha-amylase and alpha-glucosidase inhibition assays were determined as described previously by Laaroussi \u003cem\u003eet al\u003c/em\u003e. [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eExperimental Design\u003c/h3\u003e\n\u003cp\u003eTwenty-five male Wistar rats weighing 150.12\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1 grams, obtained from the Animal Housing Breeding Center, Department of Biology, Faculty of Sciences Dhar El Mahraz, University Sidi Mohamed Ben Abdallah, Fez, Morocco, were used for the experiments. Rats were kept in a ventilated room and lived in standard environmental conditions (22\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u0026deg;C, 55\u0026thinsp;\u0026plusmn;\u0026thinsp;5% humidity, 12 h light/dark cycles). The present work was approved by IRB/ethics committee of Sidi Mohamed Ben Abdellah University, Fez ( USMBA-SNAMOPEQ 2017-03). The manipulation of animals respected the EU Directive 2010/63/EU for animal experiments to avoid and minimize animal suffering and the number of animals experimented. All methods were performed in accordance with the relevant guidelines and regulations. The study is reported in accordance with ARRIVE guidelines (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://arriveguidelines.org\u003c/span\u003e\u003cspan address=\"https://arriveguidelines.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e).\u003c/span\u003e\u003c/p\u003e \u003cp\u003eFor the first 7 weeks, groups 2, 3,4, and 5 received only D-glucose and had free access to tap water and normal rats\u0026rsquo; chow diet. On the last day of the 7 weeks, rats in groups 3, 4, and 5 with fasting blood glucose greater than 9.4 mmol/L were treated with propolis, honey, and a mixture of honey and propolis respectively for the following 3 weeks.\u003c/p\u003e \u003cp\u003eRats were randomly allocated into 5 groups, 5 rats in each group. The treatments and applied procedures are as follows:\u003c/p\u003e \u003cp\u003eGroup 1 (control): received distal water (10 ml/kg b.wt) for 10 weeks.\u003c/p\u003e \u003cp\u003eGroup 2 (diabetic): received daily by gavage D-glucose (10 g/kg b.wt) for the first 7 weeks,\u003c/p\u003e \u003cp\u003eGroup 3 (diabetic\u0026thinsp;+\u0026thinsp;Propolis): received daily by gavage D-glucose (10 g/kg b.wt) for the first 7 weeks and treated with propolis extract (200mg/kg b.wt) for the following 3 weeks,\u003c/p\u003e \u003cp\u003eGroup 4 (diabetic\u0026thinsp;+\u0026thinsp;honey): received daily by gavage D-glucose (10 g/kg b.wt) for the first 7 weeks and treated with honey (2g/kg b.wt) for the following 3 weeks,\u003c/p\u003e \u003cp\u003eGroup 5 (diabetic, propolis, and honey): received daily by gavage D-glucose (10 g/kg b.wt) for the first 7 weeks and treated daily with 100mg/kg b.wt propolis extract\u0026thinsp;+\u0026thinsp;1g/kg b.wt honey for the following 3 weeks.\u003c/p\u003e \u003cp\u003eBlood samples, urine samples including 24-hour collection, and histopathological specimens were prepared at the end of 10 weeks.\u003c/p\u003e \u003cp\u003eThe treatment duration and honey and propolis extract doses were selected according to other studies [\u003cspan additionalcitationids=\"CR47\" citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eBiochemical analysis\u003c/h2\u003e \u003cp\u003eAspartate aminotransferases (AST), alanine aminotransferases (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), serum uric acid, serum creatinine, blood urea, total bilirubin, serum albumin, and serum protein were measured by enzymatic methods, using specific commercial reagent kits. All the kits were purchased from Bio-Maghreb Casablanca, Morocco.\u003c/p\u003e \u003cp\u003eUrine and serum sodium, potassium, chloride, and phosphorus were analyzed using the ion-selective potentiometry method (Architect c8000i biochemistry analyzer), and calcium was determined based on its reaction with Arsenazo III (2,2\u0026prime; -[1,8-Dihydroxy-3,6-disulphonaphthylene-2,7-bisazo]- bisbenzenear-sonic acid). The intensity of produced color was measured chromatically at 660/700 nm (Architect c8000i biochemistry analyzer).\u003c/p\u003e \u003cp\u003eBlood glucose and plasma insulin levels were determined by the radioimmunoassay method (Rat insulin RIA kit, Millipore, St Charles, MO, USA). Model homeostasis evaluation (HOMA-IR) (Eq.\u0026nbsp;(\u003cspan refid=\"Equ1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)), and homeostatic model-β (HOMA-β) were calculated following the formula described by Mattews \u003cem\u003eet al\u003c/em\u003e. [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. The quantitative insulin sensitivity check index (QUICKI) was determined according to Katz \u003cem\u003eet al\u003c/em\u003e.[\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e].\u003cdiv id=\"Equ1\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equ1\" name=\"EquationSource\"\u003e\n$$HOMA-IR=\\frac{Insulin \\left(\\frac{U}{L}\\right) \\times Glucose \\left(\\frac{mmol}{L}\\right)}{22.5}$$\u003c/div\u003e\u003cdiv class=\"EquationNumber\"\u003e1\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Equb\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equb\" name=\"EquationSource\"\u003e\n$$\\text{H}\\text{O}\\text{M}\\text{A}-{\\beta }=\\frac{20 \\times \\text{I}\\text{n}\\text{s}\\text{u}\\text{l}\\text{i}\\text{n} \\left(\\frac{\\text{U}}{\\text{L}}\\right)}{\\text{G}\\text{l}\\text{u}\\text{c}\\text{o}\\text{s}\\text{e} \\left(\\frac{\\text{m}\\text{m}\\text{o}\\text{l}}{\\text{L}}\\right)}- 3.5 \\left(2\\right)$$\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Equ2\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equ2\" name=\"EquationSource\"\u003e\n$$\\text{Q}\\text{U}\\text{I}\\text{C}\\text{K}\\text{I}=\\frac{1}{(\\text{log}\\text{f}\\text{a}\\text{s}\\text{t}\\text{i}\\text{n}\\text{g} \\text{i}\\text{n}\\text{s}\\text{u}\\text{l}\\text{i}\\text{n} \\text{l}\\text{e}\\text{v}\\text{e}\\text{l} \\left(\\frac{{\\mu }\\text{U}}{\\text{m}\\text{l}}\\right)+\\text{log}\\text{f}\\text{a}\\text{s}\\text{t}\\text{i}\\text{n}\\text{g} \\text{b}\\text{l}\\text{o}\\text{o}\\text{d} \\text{g}\\text{l}\\text{u}\\text{c}\\text{o}\\text{s}\\text{e} \\left(\\frac{\\text{m}\\text{g}}{\\text{d}\\text{l}}\\right))}$$\u003c/div\u003e\u003cdiv class=\"EquationNumber\"\u003e3\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eLiver, pancreas, and kidney antioxidant enzymes activities\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eAt the end of the experiment (10 weeks), the kidney, liver, and pancreas were quickly removed, placed in ice-cold saline solution and trimmed off adipose tissue then homogenized in cold phosphate-buffered saline (0.1 M; pH 7.4) and centrifuged (-4\u0026deg;C). The supernatant was collected and stored at -20\u0026deg;C for analysis of the oxidative parameters.\u003c/p\u003e \u003cp\u003eCatalase (CAT) activity was calculated according to the method of Aebi [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. A decrease in absorbance due to H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e degradation was monitored spectrophotometrically at 240 nm for 1 min and the activity was expressed as \u0026micro;molH\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e/min/mg protein. Glutathione peroxidase (GPx) activity was estimated according to the method of Wa [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. The activity was expressed as moles of GSH oxidized/min/mg protein.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003eReduced glutathione \u003cb\u003e(\u003c/b\u003eGSH) levels were measured following the protocol described by Ellman [\u003cb\u003e53\u003c/b\u003e]. Briefly, 3 mL of sulfosalicylic acid (4%) was added to 500 mL of homogenate tissues. The mixture was centrifuged at 2,500 g for 15 min and then prepared Ellman\u0026rsquo;s reagent was added to 500 mL of supernatant. The absorbance was measured at 412 nm after 10 min. Total GSH content was expressed as \u0026micro;g/gram of tissue.\u003c/p\u003e \u003cp\u003eThe formation of products of lipid peroxidation was quantified in liver and kidney tissues using the thiobarbituric acid-reactive substances (TBARS) method, as reported previously by Kassan \u003cem\u003eet al.\u003c/em\u003e [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e54\u003c/span\u003e], The absorbance was measured at 532 nm. Results were expressed as malondialehyde (MDA) concentration (nmol/g tissue).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (standard deviation). Statistical comparisons between the groups were performed with one-way analysis of variance (ANOVA) followed by the Tukey test using GraphPad Prism\u0026reg; software (version 5.0; GraphPad Software, Inc., San Diego, USA). \u003cem\u003et-test\u003c/em\u003e was used to compare two means. Significance was accepted at \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.T., H.L., A.A., N.H., H.I., A.E., I.E., B.L. designed the experimental protocols and participated in the experimental work. S.T. wrote part of the paper. N.A. analyzed the data and results, wrote the main manuscript text, and submitted the manuscript for publication. A.Al. did the statistical analysis and collected data. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no conflict of interest to be declared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eErejuwa O, Sulaiman A, Wahab S, Sirajudeen N, Salleh S, Gurtu S. Differential responses to blood pressure and oxidative stress in streptozotocin-induced diabetic Wistar-Kyoto rats and spontaneously hypertensive rats: effects of antioxidant (honey) treatment. Int J Mol Sci. 2011;12(3):1888-\u003cspan dir=\"RTL\"\u003e1\u003c/span\u003e907.\u003c/li\u003e\n\u003cli\u003eDing Y, Xu M, Lu Q, Wei P, Tan J, Liu R. \u003csup\u003e \u003c/sup\u003eCombination of honey with metformin enhances glucose metabolism and ameliorates hepatic and nephritic dysfunction in STZ-induced diabetic mice. Food Funt. 2019;10(11):7576-7587\u003c/li\u003e\n\u003cli\u003eAbdul Aziz M, Giribabu N, Rao P, Salleh N. Pancreatoprotective effects of Geniotrigona thoracica stingless bee honey in streptozotocin-nicotinamide-induced male diabetic rats. Biomed Pharmacother. 2017 ;89 (2):135-145\u003c/li\u003e\n\u003cli\u003eErejuwa O, Sulaiman A, Wahab S, Sirajudeem S, Salleh S, Gurtu S. Antioxidant protective effect of glibenclamide and metformin in combination with honey in pancreas of streptozotocin induced diabetic rats. Inter J Mol Sci. 2010;11(5):2056\u0026ndash;2066.\u003c/li\u003e\n\u003cli\u003eBahrami M, Ataie-Jafari A, Hosseini S, Foruzanfar H, Rahmani M, Pajouhi M. Effects of natural honey consumption in diabetic patients: an 8-week randomized clinical trial. Intern J Food Sci Nutr. 2009;60(7):618\u0026ndash;626.\u003c/li\u003e\n\u003cli\u003eAl-Waili NS: Intravenous and intrapulmonary administration of honey solution to healthy sheep: effects on blood sugar, renal and liver function tests, bone marrow function, lipid profile, and carbon tetrachloride-induced liver injury. J Med Food. 2003; 6:231-247.\u003c/li\u003e\n\u003cli\u003eAl-Waili NS, Salom KY, Akmal M, Al-Waili F, Al-Waili TN, Al-Waili AN, Ali A: Honey ameliorates influence of hemorrhage and food restriction on renal and hepatic functions, and hematological and biochemical variables. Int J Food Sci Nutr. 2006;57 (3):353-362.\u003c/li\u003e\n\u003cli\u003eAl-Waili NS, Salom KY, Al-Waili TN, Al-Waili AN, Akmal M, Al-Waili FS, Al-Waili HN: Influence of various diet regimens on deterioration of hepatic function and hematological parameters following carbon tetrachloride: a potential protective role of natural honey. Nat Prod Res. 2006;20 (10):1258-1264\u003c/li\u003e\n\u003cli\u003eEl-Guendouz S, Al-Waili N, Aazza S, Elamine Y, Zizi S, Al-Waili T. Antioxidant and diuretic activity of co-administration of Capparis spinosa honey and propolis in comparison to furosemide. Asian Pac J Trop Med. 2017 Oct;10(10):974-980.\u003c/li\u003e\n\u003cli\u003eErejuwa\u003csup\u003e \u003c/sup\u003e O, Gurtu S, Sulaiman S, Wahab M, Sirajudeen K, Salleh M. Hypoglycemic and antioxidant effects of honey supplementation in streptozotocin-induced diabetic rats. Int J Vitam Nutr Res. 2010 Jan;80(1):74-82\u003c/li\u003e\n\u003cli\u003eErejuwa O, Aja D\u003csup\u003e \u003c/sup\u003e, Uwaezuoke N, Nwadike K\u003csup\u003e \u003c/sup\u003e, Ezeokpo B\u003csup\u003e \u003c/sup\u003e, Akpan J, Nwobodo N\u003csup\u003e \u003c/sup\u003e, Araromi E\u003csup\u003e \u003c/sup\u003e, Asika E\u003csup\u003e. \u003c/sup\u003eEffects of honey supplementation on renal dysfunction and metabolic acidosis in rats with high-fat diet-induced chronic kidney disease. J Basic Clin Physiol Pharmacol. 2020 May 12;/j/jbcpp.ahead-of-print/jbcpp-2019-0151/jbcpp-2019-0151.xml\u003c/li\u003e\n\u003cli\u003eAl-Waili NS: Effects of honey on the urinary total nitrite and prostaglandins concentration. Int Urol Nephrol. 2005; 37:107-111.\u003c/li\u003e\n\u003cli\u003eAl-Ghamdi A, Badr G, Hozzein W, Allam A, Al-Waili N, Al-Wadaan M. Oral supplementation of diabetic mice with propolis restores the proliferation capacity and chemotaxis of B and T lymphocytes towards CCL21 and CXCL12 by modulating the lipid profile, the pro-inflammatory cytokine levels and oxidative stress. BMC Immunol. 2015;16:54. doi: 10.1186/s12865-015-0117-9.\u003c/li\u003e\n\u003cli\u003eAl-Waili N, Al-Ghamdi A, Ansari MJ. Synergistic effects of honey and propolis toward drug multi-resistant Staphylococcus aureus, Escherichia coli and Candida albicans isolates in single and polymicrobial cultures. Int J Med Sci. 2012;9 (8):793-800.\u003c/li\u003e\n\u003cli\u003eAl-Hariri M, Eldin T, Abu-Hozaifa B, Elnour A. Glycemic control and anti-osteopathic effect of propolis in diabetic rats. Diabetes Metab Syndr Obes. 2011;4 (5):377\u0026ndash;384.\u003c/li\u003e\n\u003cli\u003eLi Y, Chen M, Xuan H, Hu F. Effects of encapsulated propolis on blood glycemic control, lipid metabolism, and insulin resistance in type 2 diabetes mellitus rats. 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Appl Sci. 2019; 9: 4066. doi: 10.3390/app9194066\u003c/li\u003e\n\u003cli\u003eHern\u0026aacute;ndez-Fuentes A, Ch\u0026aacute;vez-Borges D, Cenobio-Galindo A, Zepeda-Vel\u0026aacute;zquez A, Figueira A., Jim\u0026eacute;nez-Alvarado R, Campos-Montiel R Characterization of total phenol and flavonoid contents, color, functional properties from honey samples with different floral origins. Int J Food Stud. 2021; 10:346\u0026ndash;358\u003c/li\u003e\n\u003cli\u003eAli M. Anti-diabetic potential of phenolic compounds: A review. Int J Food Prop. 2013;16:91\u0026ndash;103. doi: 10.1080/10942912.2011.595864.\u003c/li\u003e\n\u003cli\u003eZhang L, Li J, Hogan S, Chung H, Welbaum G, Zhou K. Inhibitory effect of raspberries on starch digestive enzyme and their antioxidant properties and phenolic composition. Food Chem. 2010;119:592\u0026ndash;599.\u003c/li\u003e\n\u003cli\u003eWang J\u003csup\u003e \u003c/sup\u003e, Yue X\u003csup\u003e \u003c/sup\u003e, Meng C\u003csup\u003e \u003c/sup\u003e, Wang Z\u003csup\u003e \u003c/sup\u003e, Jin X\u003csup\u003e \u003c/sup\u003e. Acute hyperglycemia may induce renal tubular injury through mitophagy inhibition. Front Endocrinol (Lausanne). 2020 16; 11:536213. doi: 10.3389/fendo.2020.536213. eCollection 2020. \u003csup\u003e \u003c/sup\u003e\u003c/li\u003e\n\u003cli\u003eMeng M, Li D, WF W. Wogonin protects against cisplatin-induced acute kidney injury by targeting RIPK1-mediated necroptosis. Lab Invest. 2018;98 (9):79\u0026ndash;94.\u003c/li\u003e\n\u003cli\u003eWu Y, Quan Q, Cao Q, Lin Y, Yue C, Bi R, Cui X. Quercetin alleviates acute kidney injury by inhibiting ferroptosis. J Adv Res. 2020: 22;28 94):231-243\u003c/li\u003e\n\u003cli\u003eJain K. Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells. J Biol Chemist. 1989;264(35):21340\u0026ndash;21345\u003c/li\u003e\n\u003cli\u003eBehrouj H, Ziamajidi N, Abbasalipourkabir R, Goodarzi MT, Saidijam M. Hypoglycemic and antioxidant effects of oral administration of garlic extract in the livers of type 1 diabetic rats. J Basic Clin Physiol Pharmacol. 2018: 24;30(2):245-250.\u003c/li\u003e\n\u003cli\u003eRamli NZ, Chin KY, Zarkasi KA, Ahmad F. A Review on the protective effects of honey against metabolic syndrome. Nutrients. 2018 Aug 2;10(8). pii: E1009. doi: 10.3390/nu10081009\u003c/li\u003e\n\u003cli\u003eEl Rabey H, Al-Seeni M, Bakhashwain S. The antidiabetic activity of Nigella sativa and propolis on streptozotocin-induced diabetes and diabetic nephropathy in male rats. Evidence-based Complement Alternat Med. 2017; 2017:5439645. doi: 10.1155/2017/5439645\u003c/li\u003e\n\u003cli\u003eFerreira-Santos P, Nunes R, De Biasio F, Spigno G, Gorgoglione D, Teixeira J. 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Quantitative insulin sensitivity check index: A simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000: 85(7); 2402\u0026ndash;2410. https://doi.org/10.1210/ jcem.85.7.6661.\u003c/li\u003e\n\u003cli\u003eAebi H. Catalase in vitro. Method Enzymol 1984: 105; 121\u0026ndash;126.\u003c/li\u003e\n\u003cli\u003eWa F. Assays of glutathione peroxidase. Methods Enzym. 1984: 105;114121.\u003c/li\u003e\n\u003cli\u003eEllman G. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959: 82;70\u0026ndash;77.\u003c/li\u003e\n\u003cli\u003eKassan M, Montero M,Sevilla M. Chronic treatment with pravastatin prevents early cardiovascular changes in spontaneously hypertensive rats. Br J Pharmacol. 2009: 158; 541\u0026ndash;547\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Nutritional parameters and antioxidant activity of propolis and honey.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"726\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"10.89655172413793%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSamples\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.068965517241379%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCarbohydrates (mg Glceq/g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.275862068965518%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSoluble Proteins (mg BSA/g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.275862068965518%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal proteins\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(%\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.10344827586207%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTPC\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(mg GAE/g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.10344827586207%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTFC\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(mg QE/g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.137931034482758%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTAA\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(mg AAE/g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.137931034482758%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDPPH\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eIC\u003csub\u003e50\u003c/sub\u003e(mg/mL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.89655172413793%\"\u003e\n \u003cp\u003ePropolis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.068965517241379%\"\u003e\n \u003cp\u003e1.57\u0026plusmn;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.275862068965518%\"\u003e\n \u003cp\u003e22.18\u0026plusmn;2.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.275862068965518%\"\u003e\n \u003cp\u003e2.32\u0026plusmn;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.10344827586207%\"\u003e\n \u003cp\u003e65.22\u0026plusmn;3.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.10344827586207%\"\u003e\n \u003cp\u003e25.98\u0026plusmn;5.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.137931034482758%\"\u003e\n \u003cp\u003e79.12\u0026plusmn;7.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.137931034482758%\"\u003e\n \u003cp\u003e0.34\u0026plusmn; 0.03\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.89655172413793%\"\u003e\n \u003cp\u003eHoney\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.068965517241379%\"\u003e\n \u003cp\u003e698.19\u0026plusmn;5.22a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.275862068965518%\"\u003e\n \u003cp\u003e3.42\u0026plusmn;0.01a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.275862068965518%\"\u003e\n \u003cp\u003e0.36\u0026plusmn;0.01a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.10344827586207%\"\u003e\n \u003cp\u003e28.54\u0026plusmn;1.04a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.10344827586207%\"\u003e\n \u003cp\u003e16.35\u0026plusmn;1.19a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.137931034482758%\"\u003e\n \u003cp\u003e68.72\u0026plusmn;6.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.137931034482758%\"\u003e\n \u003cp\u003e1.11\u0026plusmn; 0.01a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.89655172413793%\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.068965517241379%\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.275862068965518%\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.275862068965518%\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.10344827586207%\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.10344827586207%\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.137931034482758%\"\u003e\n \u003cp\u003e0.112\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.137931034482758%\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ea: significant compared to propolis.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e.\u0026nbsp;Phenolic compounds identification and quantification of propolis and honey\u0026nbsp;using\u0026nbsp;UPLC-DAD\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"510\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCompounds\u003c/strong\u003e\u003cstrong\u003e(mg/kg)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePropolis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHoney \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;p-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAloine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003en.d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e239.51\u0026plusmn; 5.1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Catechin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e8.15\u0026plusmn;0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e9.3 \u0026plusmn; \u0026nbsp;2.0 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 0.376\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVanilic Acid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e15.04\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e5.8 \u0026plusmn; 0.2 a \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 0.001 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eo\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-Coumaric Acid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003en.d.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e13.4 \u0026plusmn; 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFerrulic Acid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e56.78\u0026plusmn;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e17.1 \u0026plusmn; 1.0a \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eEllagic Acid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e78.92\u0026plusmn;3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e27.6 \u0026plusmn; 0.3a \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNaringin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e213.76\u0026plusmn;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e11.8\u0026plusmn; 0.2 a \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHesperidin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e121.98 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003en.d\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eApigenin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e50.37 \u0026plusmn; 0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e24.8 \u0026plusmn; 0.2a \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCinnamic Acid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e42.87\u0026plusmn;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e4.7 \u0026plusmn; 0.3a \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eResveratrol\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e81.22 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e17.6 \u0026plusmn; 3.7a \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eRosmarinic Acid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e105.09 \u0026plusmn; 5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e38.4\u0026plusmn; 4.1a \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eRutin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e60.11 \u0026plusmn; 2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003en.d\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eChlorogenic acid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e11.19 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003en.d\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eQuercetin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e22.51 \u0026plusmn; 1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003en.d\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eKaempferol\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003e89.64 \u0026plusmn; 1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e14.9 \u0026plusmn;2.8a \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.27450980392157%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGallic acid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.294117647058822%\"\u003e\n \u003cp\u003en.d.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.431372549019606%\"\u003e\n \u003cp\u003e18.8 \u0026plusmn; 0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eValues of phenolic compounds are expressed in concentration (mg/kg) [mean \u0026plusmn; SD, 3 experiments]\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;n.d: not detected.\u003cem\u003e\u0026nbsp;\u003c/em\u003ea: significant compared to propolis.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e: Alpha-amylase and alpha-glucosidase inhibitory activities of propolis and honey samples. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlpha- amylase\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Alpha-glucosidase\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;P value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHoney\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e1394 \u0026plusmn; \u0026nbsp;23.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e1083 \u0026plusmn; \u0026nbsp; 31.14a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePropolis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e233 \u0026nbsp;\u0026plusmn; \u0026nbsp;8.97b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e561 \u0026nbsp;\u0026plusmn; \u0026nbsp; \u0026nbsp;27.13a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAcarbose\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e35.69 \u0026nbsp; \u0026plusmn; \u0026nbsp; 1.29b,c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e11003 \u0026nbsp; \u0026nbsp;\u0026plusmn; 6.17a,b,c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ea: significant compared to alpha-amylase activity.\u003c/p\u003e\n\u003cp\u003eb: significant compared to honey.\u003c/p\u003e\n\u003cp\u003ec: significant compared to propolis.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4:\u003c/strong\u003e Effect of interventions on blood glucose, insulin, HOMA-IR, HOMA-B, and QUICKI.\u003c/p\u003e\n\u003ctable align=\"left\" border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" width=\"71.42857142857143%\"\u003e\n \u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eF/P value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+P\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+H\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+P+H\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGlucose (mmol/l)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e5.33\u0026plusmn; 0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e9.92 \u0026nbsp;\u0026plusmn; 0.52a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e7.19 \u0026nbsp;\u0026plusmn; \u0026nbsp;0.16a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u0026nbsp;7.58 \u0026plusmn; \u0026nbsp;0.28a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e6.89 \u0026plusmn; \u0026nbsp; 0.55a,b,\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e82/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eInsulin (U/l)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e11.71 \u0026nbsp; \u0026plusmn;0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e25.22 \u0026plusmn; \u0026nbsp;0.86a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e16.19 \u0026plusmn; \u0026nbsp;0.27a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e21.42 \u0026nbsp;\u0026plusmn; 1.4a,b,c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e14.01 \u0026plusmn; \u0026nbsp; 0.62a,b,c,d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e216.6/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHOMA-IR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e2.78 \u0026nbsp;\u0026plusmn; \u0026nbsp;0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e11.13 \u0026plusmn; \u0026nbsp;0.86a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e5.17 \u0026nbsp;\u0026plusmn; 0.20a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e7.23 \u0026nbsp;\u0026plusmn; 0.75a,b,c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e4.29 \u0026plusmn; \u0026nbsp;0.36a,b,d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e165/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHOMA-B\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e40.55\u0026nbsp;\u0026plusmn;2.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e47.41 \u0026nbsp;\u0026plusmn; 2.33a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e41.51\u0026plusmn; \u0026nbsp; 0.53,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e52.96 \u0026plusmn; \u0026nbsp;2.27a,c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e37.35 \u0026plusmn; \u0026nbsp;3.86,b,d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e33.1/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eQUICKI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.16\u0026nbsp;\u0026plusmn;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.15 \u0026nbsp;\u0026plusmn; 0.007a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.15 \u0026nbsp;\u0026plusmn; 0.004a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.15 \u0026plusmn; \u0026nbsp; 0.001a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.15\u0026plusmn;\u0026nbsp;0.004a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e6/0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;H: Honey, P: Propolis, C: Control, D; D-glucose \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ea: compared to C\u003c/p\u003e\n\u003cp\u003eb: compared to D\u003c/p\u003e\n\u003cp\u003ec: compared to D +P\u003c/p\u003e\n\u003cp\u003ed: compared to D + H\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5:\u003c/strong\u003e Effect of interventions on liver function tests and lipid profile.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" width=\"71.42857142857143%\"\u003e\n \u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eF/P value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+P\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+H\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+P+H\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e46.71 \u0026nbsp;\u0026plusmn; 2.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e64.75\u0026nbsp;\u0026plusmn;\u0026nbsp;2.30a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e55.93\u0026nbsp;\u0026plusmn;\u0026nbsp;2.33a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u0026nbsp;57.36 \u0026plusmn; 3.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e54.5\u0026nbsp;\u0026plusmn;\u0026nbsp;8.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e11/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e40.19\u0026nbsp;\u0026plusmn;\u0026nbsp;3.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e48.69\u0026nbsp;\u0026plusmn;\u0026nbsp;2.6a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e44.62\u0026plusmn; \u0026nbsp;2.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e45.51 \u0026nbsp;\u0026plusmn;4.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e40.32\u0026plusmn; \u0026nbsp;4.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e5.4/0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHDL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e19.73\u0026nbsp;\u0026plusmn;\u0026nbsp;0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e13.42 \u0026nbsp;\u0026plusmn;1.36a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e16.3\u0026nbsp;\u0026plusmn;\u0026nbsp;1.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e17 \u0026plusmn; \u0026nbsp;2.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e16.68\u0026nbsp;\u0026plusmn;\u0026nbsp;1.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e9/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTG\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e27.68\u0026nbsp;\u0026plusmn;\u0026nbsp;1.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e43.31\u0026nbsp;\u0026plusmn;\u0026nbsp;2.82a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e36.71\u0026nbsp;\u0026plusmn;\u0026nbsp;3.65a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e36.77 \u0026nbsp;\u0026plusmn;4.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e36.52\u0026plusmn; \u0026nbsp;3.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e13.7/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eALT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e68.13\u0026plusmn; \u0026nbsp;2.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e94 \u0026nbsp;\u0026plusmn;3.54a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e80.2 \u0026nbsp;\u0026plusmn;2.95a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e82.88\u0026nbsp;\u0026plusmn;\u0026nbsp;2.58a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e76.5\u0026plusmn; \u0026nbsp;2.23b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e60.38/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAST\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e144.4\u0026plusmn; \u0026nbsp;6.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e198 \u0026nbsp;\u0026plusmn;5.2a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e170\u0026plusmn;\u0026nbsp;7.9b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e175 \u0026nbsp;\u0026plusmn; 11.4a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u0026nbsp;160.9 \u0026plusmn; 10.3b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e28.31/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eALP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e52.8\u0026nbsp;\u0026plusmn;\u0026nbsp;4.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e94.33\u0026nbsp;\u0026plusmn;\u0026nbsp;13.3a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e76.9\u0026nbsp;\u0026plusmn;\u0026nbsp;4.47a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e79.2 \u0026nbsp;\u0026plusmn; 8.33a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e75.6 \u0026nbsp;\u0026plusmn;6.3a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e17.85/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e59.9\u0026nbsp;\u0026plusmn;\u0026nbsp;4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e99.2 \u0026nbsp;\u0026plusmn; 10.35a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e72.27 \u0026plusmn; \u0026nbsp;8.2a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e73\u0026nbsp;\u0026plusmn;\u0026nbsp;4.3b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e72 \u0026nbsp;\u0026plusmn; 4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e22.18/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.75\u0026nbsp;\u0026plusmn;\u0026nbsp;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e1.32 \u0026nbsp;\u0026plusmn;0.07a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e1.03\u0026nbsp;\u0026plusmn;\u0026nbsp;0.04a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.92\u0026nbsp;\u0026plusmn;\u0026nbsp;0.03a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.81b\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e91.06/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlbumin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e4.39\u0026nbsp;\u0026plusmn;\u0026nbsp;0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e2.69 \u0026nbsp;\u0026plusmn;0.10a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e3.64\u0026nbsp;\u0026plusmn;\u0026nbsp;0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e3.61\u0026nbsp;\u0026plusmn;\u0026nbsp;0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e3.76\u0026nbsp;\u0026plusmn;\u0026nbsp;0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e30/0.001\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eH: Honey, P: Propolis, C: Control, D; D-glucose \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ea: compared to C\u003c/p\u003e\n\u003cp\u003eb: compared to D\u003c/p\u003e\n\u003cp\u003ec: compared to D +P\u003c/p\u003e\n\u003cp\u003ed: compared to D + H\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6\u003c/strong\u003e: Effect of interventions on kidney function tests.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" width=\"71.42857142857143%\"\u003e\n \u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eF/P value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+P\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+H\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+P+H\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eUrea (mg/dl)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e32.9 \u0026nbsp;\u0026plusmn; \u0026nbsp;4.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e74.5 \u0026nbsp;\u0026plusmn; \u0026nbsp;5.99a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e52.9 \u0026nbsp;\u0026plusmn; 10.9a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u0026nbsp; 52.8 \u0026plusmn; \u0026nbsp; 5.1a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e47.4 \u0026nbsp;\u0026plusmn; \u0026nbsp;2.9b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e25.3/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCreatinine (mg/d)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.64 \u0026plusmn; \u0026nbsp; 0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e1.23 \u0026plusmn; \u0026nbsp;0.03a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u0026nbsp;0.92 \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026plusmn;0.02a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.97 \u0026nbsp;\u0026plusmn; 0.11a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e0.81 \u0026nbsp;\u0026plusmn; 0.04a,b,c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e74.2/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eUric acid (mg/dl)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e1.8 \u0026nbsp;\u0026plusmn; \u0026nbsp;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e2.55 \u0026nbsp;\u0026plusmn; 0.28a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e2.0 \u0026nbsp; \u0026plusmn; 0.14b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e2.11 \u0026nbsp;\u0026plusmn; 0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e2.07 \u0026nbsp;\u0026plusmn; \u0026nbsp;0.06b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e16.7/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eUrine creatinine(mg/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e53.4 \u0026nbsp; \u0026plusmn; 4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e34.5 \u0026nbsp;\u0026plusmn; 4.4a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e47.5 \u0026plusmn; \u0026nbsp; \u0026nbsp;4.5b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e42.73 \u0026plusmn; \u0026nbsp;8.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e47.8 \u0026nbsp; \u0026plusmn; 2.85b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e8.84/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eUrine uric acid (mg/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e8.53 \u0026nbsp;\u0026plusmn; 0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e12.34 \u0026plusmn; \u0026nbsp;0.53a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e9.83 \u0026nbsp;\u0026plusmn; \u0026nbsp;0.43b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e10.23 \u0026nbsp;\u0026plusmn; 0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e9.99 \u0026plusmn; \u0026nbsp;0.57b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e63.99/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u003cstrong\u003eUrine protein (mg/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e27.3 \u0026nbsp;\u0026plusmn; 2.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e36.53\u0026plusmn; \u0026nbsp; 1.9a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e29.9 \u0026nbsp; \u0026plusmn;2.4b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e32.27\u0026plusmn; \u0026nbsp; 0.8b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e\u0026nbsp;30.3 \u0026plusmn; \u0026nbsp;2.0b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.285714285714286%\"\u003e\n \u003cp\u003e15.94/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eH: Honey, P: Propolis, C: Control, D; D-glucose \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ea: compared to C\u003c/p\u003e\n\u003cp\u003eb: compared to D\u003c/p\u003e\n\u003cp\u003ec: compared to D +P\u003c/p\u003e\n\u003cp\u003ed: compared to D + H\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 7\u003c/strong\u003e: Effects of the interventions on blood and urine electrolytes.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"662\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003e\u003cstrong\u003eElectrolytes (mmol/l)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.293051359516616%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSodium\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePotassium\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.45015105740181%\"\u003e\n \u003cp\u003e\u003cstrong\u003eChloride\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePhosphorous\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCalcium\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum level\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.293051359516616%\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026nbsp;145.85 \u0026plusmn; 7.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e4.45 \u0026plusmn; 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.45015105740181%\"\u003e\n \u003cp\u003e105.00 \u0026plusmn; 8.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e\u0026nbsp;2.17 \u0026plusmn; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e2.82 \u0026plusmn; 0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.293051359516616%\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e130.50 \u0026plusmn; 5.12a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e4.17 \u0026plusmn; 0.09a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.45015105740181%\"\u003e\n \u003cp\u003e107.12 \u0026plusmn; 5.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e\u0026nbsp;2.01 \u0026plusmn; 0.03a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e2.75 \u0026plusmn; 0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.293051359516616%\"\u003e\n \u003cp\u003eD+P\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026nbsp;137.64 \u0026plusmn; 5.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e4.48 \u0026plusmn; 0.03b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.45015105740181%\"\u003e\n \u003cp\u003e104.50 \u0026plusmn; 5.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e\u0026nbsp;2.09 \u0026plusmn; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e2.81 \u0026plusmn; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.293051359516616%\"\u003e\n \u003cp\u003eD+H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026nbsp;147.28 \u0026plusmn; 6.38c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e4.43\u0026plusmn;0.03b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.45015105740181%\"\u003e\n \u003cp\u003e\u0026nbsp; 113.00 \u0026plusmn; 7.212\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e2.15 \u0026plusmn; 0.05b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e2.85 \u0026plusmn; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.293051359516616%\"\u003e\n \u003cp\u003eD+P+H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026nbsp;141.12 \u0026plusmn; 4.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e4.56\u0026plusmn; 0.07b,d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.45015105740181%\"\u003e\n \u003cp\u003e108.76 \u0026plusmn; 6.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e2.13 \u0026plusmn; 0.02b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e2.82 \u0026plusmn; 0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.293051359516616%\"\u003e\n \u003cp\u003eF/P value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e6.99/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e30/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.45015105740181%\"\u003e\n \u003cp\u003e1.46/0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e25/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e2.81/0.052\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003e\u003cstrong\u003eUrinary level\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.293051359516616%\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026nbsp;90.41 \u0026plusmn; 4.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e60.84 \u0026plusmn; 3.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.45015105740181%\"\u003e\n \u003cp\u003e82.16 \u0026plusmn; 3.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e1.28 \u0026plusmn; 0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e2.63 \u0026plusmn; 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.293051359516616%\"\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e110.58 \u0026plusmn; 1.23a\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e60.91 \u0026plusmn; 5.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.45015105740181%\"\u003e\n \u003cp\u003e82.10\u0026plusmn; 7.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e1.26 \u0026plusmn; 0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e2.70 \u0026plusmn; 0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.293051359516616%\"\u003e\n \u003cp\u003eD+P\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026nbsp;88.34 \u0026plusmn; 6.41b\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e\u0026nbsp;60.85 \u0026plusmn;4.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.45015105740181%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 80.14 \u0026plusmn; 5.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e1.28 \u0026plusmn; 0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e2.67 \u0026plusmn; 0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.293051359516616%\"\u003e\n \u003cp\u003eD+H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026nbsp;101.62 \u0026plusmn; 7.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e60.82 \u0026plusmn; 2.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.45015105740181%\"\u003e\n \u003cp\u003e86.92\u0026plusmn; 5.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e1.27 \u0026plusmn; 0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e2.69 \u0026plusmn; 0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.293051359516616%\"\u003e\n \u003cp\u003eD+P+H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026nbsp;97.13 \u0026plusmn; 6.58\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e60.88 \u0026plusmn; 3.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.45015105740181%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;83.17 \u0026plusmn; 4.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e1.30 \u0026plusmn; 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e2.61 \u0026plusmn; 0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.293051359516616%\"\u003e\n \u003cp\u003eF/P value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e12.1/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e0.06/0.992\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.45015105740181%\"\u003e\n \u003cp\u003e1.122/0.374\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e0.60/0.664\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.709969788519638%\"\u003e\n \u003cp\u003e1.47/0.248\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eH: Honey, P: Propolis, C: Control, D; D-glucose \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ea: compared to C\u003c/p\u003e\n\u003cp\u003eb: compared to D\u003c/p\u003e\n\u003cp\u003ec: compared to D +P\u003c/p\u003e\n\u003cp\u003ed: compared to D + H\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 8\u003c/strong\u003e: Effect of interventions on D-glucose-induced changes in antioxidant enzymes, proteins, and MDA concentrations in pancreatic tissues.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"16.185897435897434%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters/ pancreatic tissue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" width=\"69.87179487179488%\"\u003e\n \u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e\u003cstrong\u003eF/P value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.954128440366972%\"\u003e\n \u003cp\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.954128440366972%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.954128440366972%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+P\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.954128440366972%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+H\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.18348623853211%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+P+H\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.185897435897434%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGSH (ug/g tissue)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e33.1\u0026plusmn; \u0026nbsp;4.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e11.85 \u0026nbsp;\u0026plusmn; 0.28a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e29.48 \u0026nbsp;\u0026plusmn; 6.5b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e\u0026nbsp;23.0 \u0026plusmn; \u0026nbsp;6.5b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.102564102564102%\"\u003e\n \u003cp\u003e\u0026nbsp;28 \u0026plusmn; \u0026nbsp; 2.94b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e15.2/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.185897435897434%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGPx (nmol GSH/min/mg prt)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e12.66\u0026nbsp;\u0026plusmn;\u0026nbsp;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e4.45 \u0026plusmn; \u0026nbsp;0.35a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e7.47 \u0026plusmn; \u0026nbsp;1.17b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e7.97 \u0026plusmn; \u0026nbsp;2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.102564102564102%\"\u003e\n \u003cp\u003e8.37 \u0026nbsp;\u0026plusmn; 1.06b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e13.76/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.185897435897434%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMDA (nmol/g tissue)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e28.84\u0026plusmn; \u0026nbsp; 8.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e58.26\u0026nbsp;\u0026plusmn;\u0026nbsp;8.97a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e37.7 \u0026plusmn; \u0026nbsp;4.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e31.73 \u0026plusmn; \u0026nbsp;4.47b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.102564102564102%\"\u003e\n \u003cp\u003e33.17 \u0026plusmn; \u0026nbsp;6.6b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e12.11/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.185897435897434%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCAT (\u0026micro;mol H2O2/min/mg prt)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e20.54 \u0026nbsp; \u0026plusmn; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e11.25 \u0026nbsp;\u0026plusmn; 1.47a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e17.6 \u0026nbsp;\u0026plusmn; 1.66b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e16.5 \u0026nbsp; 0.43b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.102564102564102%\"\u003e\n \u003cp\u003e18.49 \u0026plusmn; \u0026nbsp; 1.5b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e20.6/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.185897435897434%\"\u003e\n \u003cp\u003e\u003cstrong\u003eProtein (mg/g tissue)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e7 \u0026nbsp;\u0026plusmn; \u0026nbsp;0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e5.48 \u0026nbsp;\u0026plusmn; 0.03a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e5.75 \u0026plusmn; \u0026nbsp;0.31a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e5.27\u0026plusmn; \u0026nbsp; 0.1a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.102564102564102%\"\u003e\n \u003cp\u003e6.5 \u0026plusmn; \u0026nbsp;0.16 b,c,d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.942307692307692%\"\u003e\n \u003cp\u003e53.6/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eH: Honey, P: Propolis, C: Control, D; D-glucose \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ea: compared to C\u003c/p\u003e\n\u003cp\u003eb: compared to D\u003c/p\u003e\n\u003cp\u003ec: compared to D +P\u003c/p\u003e\n\u003cp\u003ed: compared to D + H\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 9\u003c/strong\u003e: Effect of interventions on\u0026nbsp;D-glucose-induced changes in antioxidant enzymes, proteins, and MDA concentrations in liver tissues.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"16.21187800963082%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters/ liver tissue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" width=\"69.82343499197432%\"\u003e\n \u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"13.964686998394864%\"\u003e\n \u003cp\u003e\u003cstrong\u003eF/P value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.81566820276498%\"\u003e\n \u003cp\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.81566820276498%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.046082949308754%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+P\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.046082949308754%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+H\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.276497695852534%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+P+H\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.237942122186496%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGSH (ug/g tissue)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e16.0 \u0026nbsp; \u0026plusmn;1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e12.36\u0026plusmn; \u0026nbsp; 2.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e15.2 \u0026nbsp; \u0026plusmn; 2.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e15.48 \u0026nbsp;\u0026plusmn; \u0026nbsp;1.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.14790996784566%\"\u003e\n \u003cp\u003e15.66 \u0026nbsp;\u0026plusmn; \u0026nbsp;2.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e2.56/0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.237942122186496%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGPx (nmol GSH/min/mg prt)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e10.38 \u0026nbsp;\u0026plusmn; 0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e5.56 \u0026nbsp; \u0026plusmn;0.27a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e8.18 \u0026plusmn; \u0026nbsp;0.2b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e9.81 \u0026nbsp;\u0026plusmn; 1.2b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.14790996784566%\"\u003e\n \u003cp\u003e11.96 \u0026plusmn; \u0026nbsp; 2.33b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e7.18/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.237942122186496%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMDA (nmol/g tissue)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e40.58 \u0026plusmn; \u0026nbsp;11.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e70.2 \u0026nbsp;\u0026plusmn; \u0026nbsp;12a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e49.87 \u0026plusmn; \u0026nbsp;12.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e46.87 \u0026nbsp;\u0026plusmn; 5b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.14790996784566%\"\u003e\n \u003cp\u003e47.6 \u0026nbsp;\u0026plusmn; \u0026nbsp;6.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e6.56/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.237942122186496%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCAT (\u0026micro;mol H2O2/min/mg prt)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e27.28\u0026plusmn; \u0026nbsp; \u0026nbsp;5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e14.6 \u0026nbsp;\u0026plusmn; 2.1a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e20.85 \u0026nbsp;\u0026plusmn; \u0026nbsp;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e30.3 \u0026nbsp;\u0026plusmn; \u0026nbsp;6.32b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.14790996784566%\"\u003e\n \u003cp\u003e23.9 \u0026plusmn; \u0026nbsp;2.22b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e11.49/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.237942122186496%\"\u003e\n \u003cp\u003e\u003cstrong\u003eProtein (mg/g tissue)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e6.4 \u0026plusmn; \u0026nbsp; 0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e4.44 \u0026nbsp;\u0026plusmn; 0.21a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e5.1 \u0026nbsp; \u0026plusmn; 0.17a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e5.33\u0026plusmn; \u0026nbsp; 0.17a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.14790996784566%\"\u003e\n \u003cp\u003e5.2\u0026plusmn; \u0026nbsp; 0.5a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e34/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eH: Honey, P: Propolis, C: Control, D; D-glucose \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ea: compared to C\u003c/p\u003e\n\u003cp\u003eb: compared to D\u003c/p\u003e\n\u003cp\u003ec: compared to D +P\u003c/p\u003e\n\u003cp\u003ed: compared to D + H\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 10\u003c/strong\u003e: Effect of interventions on\u0026nbsp;D-glucose induced changes in antioxidant enzymes, proteins, and MDA concentrations in kidney tissues.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"16.21187800963082%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters/ Kidney tissue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" width=\"69.82343499197432%\"\u003e\n \u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"13.964686998394864%\"\u003e\n \u003cp\u003e\u003cstrong\u003eF/P value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"19.81566820276498%\"\u003e\n \u003cp\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.81566820276498%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.046082949308754%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+P\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.046082949308754%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+H\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.276497695852534%\"\u003e\n \u003cp\u003e\u003cstrong\u003eD+P+H\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.237942122186496%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGSH (ug/g tissue)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e21 \u0026nbsp;\u0026plusmn; 1.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e9.6 \u0026plusmn; \u0026nbsp; 2.4a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e16.6 \u0026nbsp; \u0026plusmn; 0.14a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e16.1 \u0026plusmn; \u0026nbsp; \u0026nbsp;2.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.14790996784566%\"\u003e\n \u003cp\u003e16.9 \u0026nbsp;\u0026plusmn; \u0026nbsp;1.42b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e25.5/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.237942122186496%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGPx (nmol GSH/min/mg prt)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e14.4 \u0026plusmn; \u0026nbsp; 1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e8 \u0026nbsp; \u0026plusmn; \u0026nbsp;1.4a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e12.8 \u0026plusmn; \u0026nbsp;2.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e11.12 \u0026nbsp;\u0026plusmn; 1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.14790996784566%\"\u003e\n \u003cp\u003e12.8 \u0026nbsp;\u0026plusmn; 1.4b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e11.03/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.237942122186496%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMDA (nmol/g tissue)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e31.7 \u0026plusmn; \u0026nbsp;3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e47.3 \u0026nbsp; \u0026plusmn; \u0026nbsp;3.3a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e43.3 \u0026plusmn; \u0026nbsp;4.0a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e35.3 \u0026nbsp; \u0026plusmn; 7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.14790996784566%\"\u003e\n \u003cp\u003e37.5 \u0026plusmn; \u0026nbsp;4.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e9.5/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.237942122186496%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCAT (\u0026micro;mol H2O2/min/mg prt)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e19.4 \u0026plusmn; \u0026nbsp; 1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e12.9 \u0026nbsp;\u0026plusmn; \u0026nbsp;0.78 a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e16.6 \u0026plusmn; \u0026nbsp; 1.86b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e15.4 \u0026nbsp;\u0026plusmn; \u0026nbsp;0.7a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.14790996784566%\"\u003e\n \u003cp\u003e16.28 \u0026plusmn; \u0026nbsp;2.4a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e10.6/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"16.237942122186496%\"\u003e\n \u003cp\u003e\u003cstrong\u003eProtein (mg/g tissue)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e5.1 \u0026nbsp; \u0026nbsp;\u0026plusmn;0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.82636655948553%\"\u003e\n \u003cp\u003e3.4 \u0026nbsp; \u0026plusmn; 0.19a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e4.1\u0026plusmn; \u0026nbsp; 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e4.56 \u0026nbsp; \u0026plusmn; 0.29b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.14790996784566%\"\u003e\n \u003cp\u003e4.33 \u0026plusmn; \u0026nbsp; 0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.987138263665594%\"\u003e\n \u003cp\u003e8.34/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eH: Honey, P: Propolis, C: Control, D; D-glucose \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ea: compared to C\u003c/p\u003e\n\u003cp\u003eb: compared to D\u003c/p\u003e\n\u003cp\u003ec: compared to D +P\u003c/p\u003e\n\u003cp\u003ed: compared to D + H\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 11\u003c/strong\u003e: level of oxidant and anti0xidants in the liver, pancreas, and kidney tissues in the control group.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"23.059866962305986%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"57.649667405764966%\"\u003e\n \u003cp\u003e\u003cstrong\u003eOrgans\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"19.290465631929045%\"\u003e\n \u003cp\u003e\u003cstrong\u003eF/P\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.204633204633204%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiver\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"33.204633204633204%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePancreas\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"33.59073359073359%\"\u003e\n \u003cp\u003e\u003cstrong\u003eKidney\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"23.11111111111111%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGSH (ug/g tissue)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.11111111111111%\"\u003e\n \u003cp\u003e16.86 \u0026plusmn; \u0026nbsp;1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.11111111111111%\"\u003e\n \u003cp\u003e33.1 \u0026plusmn; \u0026nbsp;4.07a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.333333333333332%\"\u003e\n \u003cp\u003e21\u0026plusmn; \u0026nbsp; 1.55b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.333333333333332%\"\u003e\n \u003cp\u003e58.8/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"23.11111111111111%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGPx (nmol GSH/min/mg prt)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.11111111111111%\"\u003e\n \u003cp\u003e10.38 \u0026nbsp;\u0026plusmn; 0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.11111111111111%\"\u003e\n \u003cp\u003e12.66\u0026plusmn; \u0026nbsp; \u0026nbsp;3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.333333333333332%\"\u003e\n \u003cp\u003e14.4 \u0026nbsp;\u0026plusmn; \u0026nbsp;1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.333333333333332%\"\u003e\n \u003cp\u003e4.58/0.333\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"23.11111111111111%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMDA (nmol/g tissue)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.11111111111111%\"\u003e\n \u003cp\u003e40.58 \u0026nbsp;\u0026plusmn; 11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.11111111111111%\"\u003e\n \u003cp\u003e28.84 \u0026plusmn; \u0026nbsp;8.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.333333333333332%\"\u003e\n \u003cp\u003e31.7 \u0026plusmn; \u0026nbsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.333333333333332%\"\u003e\n \u003cp\u003e2.45/0.127\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"23.11111111111111%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCAT (\u0026micro;mol H2O2/min/mg prt)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.11111111111111%\"\u003e\n \u003cp\u003e27.28 \u0026nbsp;\u0026plusmn; \u0026nbsp;5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.11111111111111%\"\u003e\n \u003cp\u003e20.54 \u0026nbsp;\u0026plusmn; \u0026nbsp;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.333333333333332%\"\u003e\n \u003cp\u003e19.4 \u0026nbsp;\u0026plusmn; \u0026nbsp;1.3a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.333333333333332%\"\u003e\n \u003cp\u003e7.5/0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"23.11111111111111%\"\u003e\n \u003cp\u003e\u003cstrong\u003eProtein (mg/g tissue)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.11111111111111%\"\u003e\n \u003cp\u003e6.4 \u0026nbsp; \u0026nbsp;\u0026plusmn;0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.11111111111111%\"\u003e\n \u003cp\u003e7 \u0026nbsp;\u0026plusmn; \u0026nbsp;0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.333333333333332%\"\u003e\n \u003cp\u003e5 \u0026nbsp; \u0026plusmn; 0.54 a,b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.333333333333332%\"\u003e\n \u003cp\u003e40/0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ea: compared to liver.\u003c/p\u003e\n\u003cp\u003eb: compared to the pancreas.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"Honey, propolis, D-glucose, antioxidant, diabetes, kidney, liver, pancreas","lastPublishedDoi":"10.21203/rs.3.rs-2697406/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2697406/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePropolis and honey possess antioxidant, hypoglycemic, and antiproteinuric effects. The study aimed to explore the effect of propolis, honey, and their combination against D-glucose-induced hyperglycemia, acute kidney injury, liver injury, dyslipidemia, and changes in the oxidants and antioxidants in renal, hepatic, and pancreatic tissues. The chemical analysis and antioxidant content of propolis and honey were studied. The inhibitory effect of propolis and honey on alpha-amylase and alpha-glucosidase activity was studied. The study included five groups of rats, four groups treated with D-glucose and one group untreated. The D-glucose treated group (diabetic group) was divided into 1-4 groups. In addition to D-glucose, groups 2,3, and 4 were treated with propolis, honey, and a combination of propolis and honey respectively. Blood glucose levels, liver and renal function tests, urine protein and electrolytes, oxidant and antioxidant parameters, and histopathological changes in hepatic, renal, and pancreatic tissues were studied. Treatment with D-glucose continued for seven weeks, and with other interventions for the following 3 weeks. Propolis has a higher level of total protein and antioxidant activity than honey while honey contains higher carbohydrate levels. Honey has a higher alpha-amylase and glucosidase inhibitory activity than propolis. D-glucose caused a significant elevation of blood glucose, insulin, HOMA, blood urea, creatinine, lipid parameters, liver enzymes, and urine protein level. It significantly increases MDA and decreases antioxidant parameters in pancreatic, hepatic, and renal tissues. D-glucose caused histopathological changes in hepatic, renal, and pancreatic tissues. Propolis, honey, and their combination significantly ameliorated these changes. Propolis, honey, or their combination treated hyperglycemia, acute kidney injury, proteinuria, liver injury, and dyslipidemia, induced by D-glucose, most likely, by antioxidant activity and alpha-amylase and alpha-glucosidase inhibitory activity.\u003c/p\u003e","manuscriptTitle":"The effect of propolis and honey on oxidant and antioxidant parameters and D-glucose induced hyperglycemia, acute kidney injury and proteinuria in rats","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-03-31 14:47:08","doi":"10.21203/rs.3.rs-2697406/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":"764803ad-db6e-4fa5-8e32-2a34beab30fc","owner":[],"postedDate":"March 31st, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":20311141,"name":"Biological sciences/Biochemistry"},{"id":20311142,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2023-05-20T08:44:17+00:00","versionOfRecord":[],"versionCreatedAt":"2023-03-31 14:47:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2697406","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2697406","identity":"rs-2697406","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}