Phytochemical Analysis, Antioxidant, Anticholinergic, Antidiabetic, and Antiglaucoma Potentials of Sage (Salvia adiyamanensis)

Phytochemical Analysis, Antioxidant, Anticholinergic, Antidiabetic, and Antiglaucoma Potentials of Sage (Salvia adiyamanensis) | 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 Phytochemical Analysis, Antioxidant, Anticholinergic, Antidiabetic, and Antiglaucoma Potentials of Sage (Salvia adiyamanensis) Ahmet Zafer TEL, Kubra ASLAN, Ilhami GULCIN This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6213034/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 In this study, the antioxidant effect of ethanolic extracts were prepared from the aerial part of Salvia adiyamanensis was investigated through five methods, including DPPH⋅, ABTS, and Fe 3+ , Cu 2+ , Fe 3+ -TPTZ reducing assays. The IC50 values of extract was determined as 35.40 ± 8.35 and 29.50 ± 5.12 µg/mL for DPPH and ABTS radicals scavenging assays. The enzyme inhibition property of the extract was investigated against α-glycosidase, acetylcholinesterase, butyrylcholinesterase, human carbonic anhydrase I, and human carbonic anhydrase II, as a result, IC 50 values were determined as 30.78, 191.3, 8.02, 32.68 and 54.82 µg/mL, respectively. LC-MS/MS revealed that S. adiyamanensis compromised the characteristic phenolics including rosmarinic acid, chlorogenic acid, luteolin, quercetin, apigenin, and caffeic acid of the Salvia genus. These findings strongly suggest that S. adiyamanensis has the potential to be a natural medicine for the treatment of metabolic diseases such as diabetes, Alzheimer’s disease, or glaucoma. Biological sciences/Biochemistry Biological sciences/Biological techniques Physical sciences/Chemistry S. adiyamenensis phytochemical profiling antioxidant capacity enzyme inhibition metabolic disease Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Salvia , also known as sage, species are a subgroup of the Lamiaceae family that grows in temperate and warmer regions including the Mediterranean, Central Asia, the Pacific Islands, tropical Africa, and America 1 . According to the Plant of World Online database, 1024 species are accepted worldwide. Common or medicinal sage ( S. officinalis ), steppe sage ( S. stepposa) , clary or musk sage ( S. sclarea) , desert sage ( S. deserta ), woodland sage, blue sage or wild sage ( S. nemorosa) , lilac sage ( S. verticillata) , Mediterranean sage or African sage S. aethiopis , Spanish sage ( S. lavandulaefolia) , Lebanese sage (S. libanotica) and Chinese sage (S. miltiorrhiza) are among the salvia types that are distinguished with their valuable benefits to the human as a flavoring agent in food, cosmetic and traditional medicine 2 . S. officinalis , S. lavandulaefolia , and S. miltiorrhiza have been used for centuries as restoratives for lost or declining mental functions such as in Alzheimer’s disease (AD) 3 . S. libanotica has been used for many years to cure diseases such as abdominal pains, headaches, indigestion, and heart disorders 3 . S. officinalis has been traditionally used to treat menopausal syndromes, for that matter, once-daily application of the fresh sage extract evaluated as clinically valuable in terms of safety, efficacy, and tolerability in the treatment of menopausal symptoms 3 , 4 . Danshen is an S. miltiorrhiza- originated medicinal herb that possesses broad cardiovascular and cerebrovascular protective actions and has been used in Asian countries for many centuries 5 . In addition to these, a wide range of antimicrobial, antioxidant activity, anti-inflammatory, antinociceptive, antimutagenic, anticancer, anti-diarrheal, cholesterol-lowering, and anti-diabetic activities of different sage have been reported so far 4 – 15 . The importance of sage is not limited to its medicinal use but also its use in food and cosmetics. Due to the rich antioxidant and antimicrobial metabolite content, much research has focused on the integration of Salvia into food preservation including processed meat and milk from peroxidation and microbial growth 4 , 16 . Besides, antimicrobial activity is one of the most cited bioactivities of Salvia essential oils (EOs), including against bacteria and fungi; e.g., S. amplexicaulis, S. officinalis , therefore, application of salvia EOs and extracts to cosmetic formulation is highly demanded 16 . Current studies have been focusing on enzyme inhibitory properties against the enzymes including collagenase and elastase with remarkable effects for derma cosmetic applications, besides, some acne and wound healing activities in both in vivo and in vitro studies have been reported 17 – 19 . Different formulations for targeted delivery, and more eligible physicochemical properties including solubility, swelling, and surface/volume ratios have been developed by researchers to increase the effective usage of these versatile plant extracts 18 , 20 . The published literature reports that lipophilic constituents as well as hydrophilic constituents contribute to the biological actions of salvia 3 , 5 , 21 . Phytochemical analyses made today revealed that the main constituents of salvia species are diterpenes being the largest group and the others being less abundant are the monoterpenes, sesquiterpenes, sesterterpenes, triterpenes, steroids, and phenols. Among diterpenes, abietane diterpenes are the largest group of known Salvia diterpenes. In recent years, much effort has been invested to identify water-soluble Salvia constituents, such as phenolic acids and flavonoids 8 , 11 , 22 . The main phenolic of Salvia is caffeic acid which plays a central role in synthesizing the simple monomers into oligomers, followed by caffeic acid and 3-(3,4-dihydroxyphenyl) lactic acid, ferulic acid, isoferulic acid, chlorogenic acid. The majority of antioxidant activity and therapeutic activity of salvia species originates from rosmarinic acid, dimer, and salvianolic acid B, a tetramer of caffeic acid 2 , 21 . The most representative flavonoids are flavones of apigenin and luteolin and their corresponding 6-hydroxylated derivatives, flavonols, and their glycosides. The flavonoids luteolin, quercetin, salvigenin identified in several Salvia species 21 . The diverse array of bioactive compounds present in plants has long attracted the attention of the scientific community due to their potential beneficial effects on human health. Among these compounds, antioxidants-a group of molecules capable of inhibiting or delaying oxidative processes-have emerged as key players in the prevention and management of various chronic diseases 23 .Research over the past several decades has increasingly focused on plant-derived antioxidants, as numerous studies have demonstrated their ability to neutralize free radicals and reduce oxidative stress, which is implicated in the pathogenesis of conditions such as cardiovascular disease, cancer, and neurodegenerative disorders 24 . Plants synthesize an impressive range of antioxidant compounds as part of their secondary metabolism. These compounds include polyphenols, flavonoids, carotenoids, vitamins, and other phytochemicals that not only contribute to the plant’s own defense mechanisms against environmental stressors but also confer significant health benefits when consumed 25 , 26 . Polyphenols, for example, are well recognized for their potent free radical and reactive oxygen species (ROS) scavenging abilities and are abundant in fruits, vegetables, teas, and wines. Flavonoids, a major subclass of polyphenols, have been extensively studied for their anti-inflammatory, anti-carcinogenic, and cardioprotective properties 27 . Advancements in analytical techniques have significantly enhanced our ability to assess the antioxidant capacity of plant extracts and isolated compounds. Standard assays such as the ferric reducing ability, and radical scavenging assay provide quantitative measures of antioxidant potential 28 . These methods have been pivotal in establishing a link between in vitro antioxidant activities and the potential in vivo effects of plant-based compounds. However, a major challenge remains in correlating these assay results with the complex biological processes in humans. Factors such as bioavailability, metabolism, and the synergistic interactions among multiple antioxidants in the diet complicate the translation of laboratory findings to real-world health outcomes 29 , 30 . Epidemiological studies consistently underscore the health benefits of diets rich in plant-based foods. Populations that consume a high intake of fruits, vegetables, nuts, and whole grains typically exhibit lower incidences of chronic diseases, a phenomenon partly attributed to the high levels of naturally occurring antioxidants 31 . Numerous clinical and experimental investigations have revealed that these bioactive compounds not only mitigate oxidative damage but also modulate key cellular signaling pathways, influence gene expression, and even induce apoptosis in malignant cells. Such findings suggest that the protective effects of plant antioxidants extend beyond mere free radical scavenging, offering a multifaceted approach to disease prevention and health promotion 31 , 32 . Moreover, the application of plant-derived antioxidants is not limited solely to health and nutrition. In the food industry, these natural compounds are increasingly employed as alternatives to synthetic preservatives, thereby enhancing the shelf life and safety of various products without the adverse effects sometimes associated with chemical additives 33 . In summary, the exploration of plant content and its antioxidant properties represents a vibrant and essential field of research. The growing body of literature highlights the significant role that plant antioxidants play in neutralizing free radicals and mitigating oxidative stress, ultimately contributing to the prevention of a wide range of chronic diseases 34 , 35 .While in vitro studies and epidemiological data provide strong evidence for these benefits, future research must aim to elucidate the precise mechanisms by which these compounds exert their effects in vivo. A deeper understanding of these processes will not only validate the health claims associated with antioxidant-rich diets but also pave the way for the development of novel therapeutic strategies derived from nature’s own pharmacopeia. This comprehensive view reinforces the importance of dietary diversity and underscores the potential of plant-based interventions in promoting overall health and longevity 36 . Acetylcholinesterase (AChE) is a crucial enzyme responsible for terminating synaptic transmission by catalyzing the rapid hydrolysis of the neurotransmitter acetylcholine (ACh) 37 . Inhibition of AChE results in elevated levels of acetylcholine at synapses, thereby enhancing cholinergic neurotransmission. This pharmacological strategy is particularly significant in the treatment of neurodegenerative disorders such as Alzheimer’s disease (AD), where drugs like donepezil, rivastigmine, and galantamine serve as reversible AChE inhibitors to improve cognitive function and memory 38 , 39 . Additionally, AChE inhibitors are employed in the management of conditions like myasthenia gravis and as antidotes against organophosphate poisoning. The development and optimization of these inhibitors have been driven by detailed studies of the enzyme’s structure, kinetics, and role in neural function 40 , 41 . Ongoing investigations continue to refine these agents, aiming to maximize clinical benefits while minimizing adverse effects 42 . α-Glycosidase is an enzyme that plays a critical role in carbohydrate digestion by hydrolyzing complex carbohydrates and disaccharides into simple sugars in the gastrointestinal tract 43 , 44 . The regulation of α-glycosidase activity is particularly important in diabetes management, as excessive carbohydrate digestion leads to rapid glucose absorption, resulting in postprandial hyperglycemia. Inhibiting α-glycosidase with drugs such as acarbose and miglitol has become an effective therapeutic strategy for controlling blood sugar levels in individuals with type-2 diabetes (T2DM) 45 , 46 . These inhibitors slow the breakdown of carbohydrates, thereby reducing the post-meal rise in blood glucose. Several studies have highlighted the beneficial effects of α-glycosidase inhibitors in improving glycemic control, decreasing insulin resistance, and even possibly delaying the progression of diabetes complications 44 . Carbonic anhydrases (CAs) are metalloenzymes that catalyze the reversible conversion of carbon dioxide and water to bicarbonate (HCO 3 − ) and a proton 47 , 48 . In the context of glaucoma, the most relevant form is carbonic anhydrase II (CA II), which plays a critical role in the regulation of aqueous humor production in the eye 31 , 49 . Inhibition of CA reduces the production of HCO 3 − ions, leading to a decrease in aqueous humor secretion and consequently lowering intraocular pressure (IOP). This reduction in IOP helps manage glaucoma, particularly primary open-angle glaucoma, by preventing optic nerve damage caused by elevated pressure 50 , 51 . Two commonly used CA inhibitors (CAIs), acetazolamide and dorzolamide, have been shown to effectively reduce IOP and are commonly employed in both oral and topical forms as adjunctive therapies 52 , 53 . However, long-term use of CAIs may be associated with side effects such as metabolic acidosis and kidney stones. Ongoing research continues to focus on improving the efficacy and minimizing the adverse effects of CA inhibitors in the treatment of glaucoma 42 . In the present study, it was aimed to explore the phytochemistry and biological activity of a novel species of Salvia ( Salvia adiyamanensis İlçim & Tel sp. nova ) collected from the Adiyaman province in Southeastern Anatolia, Turkey, which is considered to be the center of Salvia diversity 54 . This new species is related to S. cassia which is restricted to Amanos mountains, particularly south and south-east of Turkey 54 .By analyzing the chemical composition through chromatographic and spectroscopic methods and examining the biological properties of ethanolic extracts from this plant, we sought to uncover its potential industrial applications and reveal the relativeness to the other members of the Salvia genus. Our research focused on several key biological activities, including antioxidant, anti-cholinergic, antidiabetic, and antiglaucoma effects. Through these investigations, we aimed to shed light on the plant’s phytochemical profile and assess its viability as a source of natural bioactive compounds with promising health benefits. MATERIAL AND METHODS 2.1. Plant Material&Chemicals Salvia adiyamanensis İlçim & Tel collection coordinates are 37˚ 53’ 27 N- 38˚ 17’ 46 E. Adıyaman to Malatya road 17.km, between Rezip-Semikhan villages. Habitat was defined as Rocky steppe with 1070 m altitude. The plant was classified as a local endemic and the International Union for Conservation of Nature category was determined as Critically endangered 54 . The species was registered to the Adıyaman University Herbarium with fixture number 1395 by Plant Taxonomist Prof. Dr. Ahmet Zafer TEL. Standard phenolics used in LC/MS-MS calibration and validation were purchased from Sigma Aldrich GmbH (Steinheim, Germany). Acetylcholinesterase (AChE) from Electrophorus electricus (electric eel) Type VI-S lyophilized powder 200–1000 U/mg protein, Butyrylcholinesterase (BChE) from equine serum lyophilized powder ≥ 900 units/mg protein, Alpha-Glucosidase Type I From Bakers Yeast 100 UN were purchased Sigma Aldrich GmbH. Human carbonic anhydrase I and II isoenzymes (hCAI ve hCA II) were isolated from human erythrocytes through hemolysis, purified by affinity column chromatography, and characterized by SDS-PAGE as previously applied 55 , 56 . Acetylthiocholine iodide 99.0% (AT), Butyrylthiocholine iodide (BT) ≥ 98%, 5,5'-Dithiobis (2-Nitrobenzoic Acid), 4-Nitrophenyl β-D-glucopyranoside (p-NPG) ≥ 98% (TLC), 4-Nitrophenyl acetate (p-NFA) ≥ 99.0% (GC) were purchased from Sigma Aldrich. Other used but not mentioned chemicals are of analytical grade. 2.2. Preparation of S. adiyamanensis ethanol extracts Ethanol extracts of S. adiyamanensis were prepared by weighing 25 g of dried aerial parts of the plant. Then, 100 mL of ethanol was added to the milled plant material in a beaker and the sample was mixed for 5 hours for the preparation of ethanol extracts. Ethanol was removed from the extracts by rotary evaporator. The overall extraction yields were calculated by dividing the remaining extracts by the quantity of the starting dried plant. 100 mg of dry extracts were separated for LC-MS/MS analysis, and an ethanol and DMSO solution of extracts concentrated between 15–45 µg/mL was prepared for further antioxidant capacity, and enzyme inhibition tests. 2.3. Phytochemical Analysis of The Extracts 2.3.1. Total flavonoid and total phenol content of S. adiyamanensis extracts The samples' total flavone and flavonol contents were determined by analyzing through the Al(NO 3 ) 3 colorimetric method 57 . 1 mg of extracts in 0.5 mL ethanol was mixed with 1.5 mL of 95% methanol. Then, 0.5 mL of 1.0 M potassium acetate, 2.3 ml of distilled water, and 1.5 mL of 10% Al (NO 3 ) 3 were added to the reaction mixture, and the samples were incubated at 25 o C for 40 min after vigorously shaking. Nitrates in the method serve as nitrating agents for romatic vicinal diols to produce a flavonoid-nitroxyl derivative that can be measured spectrophotometrically 46,58,59 . Absorbances of each reaction at 415 nm were recorded, and the results were expressed as µg quercetin equivalents (QE)/mg of S. adiyamanensis extract. A standard curve of quercetin was obtained within a concentration range of 1-500 µg/mL. The total phenolic content of 1 mg plant extract was determined by the Folin-Ciocalteu (FC) method applied by Karagecili et al. (2023a) splitting the volumes of each component by half 57,59 . the FC assay is based on the reduction of a yellow phosphotungstate–phosphomolybdate complex by antioxidants (reductants) to a blue chromogen that can be measured spectrophotometrically at 760 nm 59,60 . 2.3.2. Screening of Polyphenolics of S. adiyamanensis Extracts by LC-MS/MS Thirty-five phenolic compounds were quantified in total by liquid chromatography (Agilent Technologies 1290 Infinity UHPLC chromatography, Palo Alto, USA) followed by electrospray ionization (ESI) MS-MS (Agilent 6460 mass spectrometer, Palo Alto, USA). UHPLC-ESI-MS/MS data were acquired and processed by MassHunter Qualitative Analysis B07 and MassHunter Quantitative Analysis B07 software (Agilent, USA). The LC-MS/MS method was applied as previously reported and adopted for dried samples of ethanolic S. adiyamanensis 61,62 . 2.4. Determination of Antioxidant Properties of S. adiyamanensis 2.4.1. DPPH and ABTS Radical Scavenging Activity DPPH Radical scavenging activity determination assay was performed as previously applied 57,63 . An ethanol solution of 0.5 mM DPPH was prepared and incubated in the dark by mixing overnight for pre-radicalization. Then, 0.5 mL of DPPH and 0.5 mL of the S. adiyamanensis samples in ethanol (15-45 µg/mL) were mixed and incubated at 30 o C for 30 minutes. The sample contains DPPH and ethanol used as a control reaction. The absorbances of each sample were recorded at 517 nm and a decrease in absorbance of the control reaction was accepted as a radical scavenging property 59,63,64 . ABTS radical scavenging was performed based on the bleaching ability of different concentrations of the extracts 57,65 . Pre-radicalize ABTS radicals were obtained by mixing an equal volume of 2.45 mM potassium-thiosulphate and 2 mM ABTS for 6 hours in the dark. Then, the absorbance of ABTS radical solution at 734 nm was maintained at about 1.0 by diluting the ABTS reagent with 0.1 M, pH 7.4 phosphate buffer solution (PBS). The assay was performed by incubating 1.0 mL of ABTS solution and 3.0 mL of the samples (15-45 µg/mL) in 0.1 M PBS, pH 7.4 for 30 minutes. The bleaching ability of the samples was measured by the decrease in absorbance at 734 nm. The sample contains ABTS and PBS used as a control reaction. A decrease in absorbance of the control reaction is accepted as a radical scavenging property. DPPH and ABTS assays were also performed for reference antioxidants, including ascorbic acid, BHA, BHT, α-tocopherol, and trolox. Each test was performed in triplicate. Percentages of the inhibition were calculated by using the formula; % DPPH/ABTS Scavenging = 100-(Sample’ absorbances/Control’ absorbance) x100 2.4.2. Reducing Antioxidant Capacity Test The ability of S. adiyamanensis extracts to reduce metal complexes was investigated with three different methods which are performed in triplicate for each sample and compared with the positive controls, BHA, BHT, alpha-tocopherol, and trolox. Fe +3 -Reducing assay : 0.75 mL of three different concentrations (15-45 µg/mL) of of S. adiyamanensis samples in distilled water were mixed with 1.25 mL of 0.20 M, PBS pH 6.6 and 1 % (w/w) potassium ferrocyanide. Then, the samples were protonated by 1. 25 mL of 10 % trichloroacetic acid (w/w) and were incubated at 50 o C for 30 min. Formed Perl’s Prussian blue complex, which gives absorption maxima at 700 nm, was measured after the addition of 0.25 mL of 0.1 % FeCl 3 65 . Spectral color changes of yellow solution into green or blue color, depending upon reducing the capacity of the samples, were observed, and reaction mixtures were analyzed against blank sample that contained distilled water instead of extract solution via Shimadzu UV-1800 UV Spectrophotometer 59 . CUPRAC assay: 0.5 mL of 10 mM of CuCl 2 , 0.5 mL of 7.5 mM neocuproine, and 0.5 mL of 1.0 M and pH 6.5 NH 4 CH 3 CO 2 buffer were mixed with the plant sample concentration between 15-45 µg/mL in ethanol. the total reaction volume was adjusted to 2 mL with distilled water. Yielded Cu 2+ from Cu + -neocuproine complex by electron donor after 30 min incubation a 25 o C was measured spectrophotometrically using the blue-colored final reaction mixture at 450 nm 57,59 . The blank sample was prepared same solution except ethanol instead of extract solution. Fe 3+ - TPTZ Reducing Assay : In acidic environments, Fe 3+ -(TPTZ) 2 complexes take one electron from a reducing agent, an antioxidant, and transform into Fe 2+ -(TPTZ) 2 complex, thereby, intensive blue color forms in the reaction mixture 65 . FRAP reagent was prepared by mixing 10 mM TPTZ (in 0.4 mM HCl): 20 mM FeCl 3 : 0.3 M pH 3.6 sodium acetate buffer in a ratio 1:1:10. Reaction components were 0.5 mL of the ethanolic samples (15-45 µg/mL in acetate buffer), 2.25 mL of 20 mM FeCl 3 and 2.25 mL FRAP reagent, resulting in a 5 mL final reaction volume 57,59,65 . The blank sample was prepared with an acetate buffer without the samples. Each reaction's absorbance was measured at 593 nm at the end of 30 min incubation at 37 o C. 2.5. Enzyme Inhibition Profiles of Ethanolic S. adiyamanensis Extracts Each inhibition study started with lower concentrations of the extract samples and subsequently increased until more of the enzyme activity was inhibited by the sample addition. The samples' IC 50 values (the concentration of compound where percent inhibition is equal to 50) were calculated using the GraphPad Prism 8.4.0 non-linear regression-[inhibitor]-normalized response (y values 100 down to 0) model. 2.5.1. Determination of α-Glycosidase Inhibition (AGI) The inhibition effect of the plant extracts over α-glycosidase was investigated by simply incorporating certain concentrations of extracts into the enzyme activity assay. α-Glycosidase enzyme activity assay principle relies on the enzymatic conversion substrate 4-nitrophenyl-α-D-glucopyranoside to α-D-glucopyranoside and p-nitrophenol, resulting yellow-colored product is measured spectrophotometrically at 405 nm 66,67 . The assay reaction consisted of 50 μL of 5 mM p-NPG, 100 μL of 0.1 M of pH 6.9 PBS, and 10 μL of enzyme solution 39,68 . Acarbose was used as a positive control for AGI. 2.5.2. Determination of AChE and BChE Inhibition Ethanolic S. adiyamanensis solutions at varying concentrations for complete inhibition were added to the reaction mixture containing 50 μL of 10 mM DTNB, 50 μL of 10 mM substrate, and 10 μL of enzyme solution in 1 mL of the reaction solution 57 . The substrate was AT for AChE and BT for BChE. Right after enzyme addition, the absorbance at 412 nm was measured for five minutes at minute intervals 57,69–71 . Control reactions and blank reactions were set up without inhibitors and enzymes, respectively. Positive control for AChE and BChE inhibition test was donepezil. 2.5.3. Determination of hCA I and II Inhibition The resulting compound after the esterase activity of the carbonic anhydrase (CA) enzyme, a yellow-colored aromatic p-nitrophenolate, gives absorption maxima at 348 nm 59,72–74 . Various concentrations of the samples in 400 μL of 0.05 M pH=7.4 Tris-SO 4 , 360 μL of 0.07 mM of p-NFA (in 1:25 acetone: water), and 10 µL of the enzyme were mixed and as soon as the addition of the enzyme, the absorbance was monitored by measuring minute intervals for three minutes at 348 nm. Control reactions and blank reactions were set up without inhibitors and enzymes, respectively. These steps were repeated until more than half of enzyme activity was inhibited. The positive control for hCA I and hCA II inhibitors was acetazolamide. 2.6. Statistical Analysis Each experiment is repeated three times. The results are given as mean ± SD. In the two-way ANOVA; the mean values of each data set were compared within columns and significant differences were considered to have a value of p <0.05. All data were processed and graphs were created using GraphPad Prism 8.4.0 RESULTS & DISCUSSION The antioxidant capacity of the S. adiyamanensis extracts was investigated through five different colorimetric methods, that rely on two different principles. The first mechanism was the bleaching ability of free radicals, which was determined through DPPH and ABTS radical scavenging assays. According to the DPPH radical scavenging assay result, ethanolic S. adiyamanensis extract was inhibited the 68 ± 0.03 of % total DPPH radical when 45 µg/mL of the sample applied and the IC 50 value of the extract was calculated as 29.50 ± 5.12, while this value was 21.52 ± 8.22 for ascorbic acid, 30.65 ± 4.89 for BHA, 26.99 ± 4.18 for BHT, and 43.26 ± 2.26 for trolox (Fig. 1 A). P value was determined as < 0.05, concluding that no significant difference between the samples was determined. As it can be concluded from these values, S. adiyamanensis extracts have remarkably slightly lower but notable DPPH radical scavenging capacity. Similarly, the ABTS radical scavenging assay yielded 74.92 ± 2.37% of scavenging of total ABTS radical by 45 µg/mL of the S. adiyamanensis extracts. IC 50 value was calculated as 35.40 ± 8.35, while this value was 10.44 ± 5.44 for ascorbic acid, 12.78 ± 5.43 for BHA, 17.81 ± 5.43 for BHT, and 8.59 ± 1.25 for trolox (Fig. 1 B) (p < 0.05). As it can be concluded from these values, S. adiyamanensis extracts have remarkable ABTS radical scavenging properties as both natural and synthetic antioxidants. Results obtained from ABTS were relatively lower, this could be the consequence of the capacity of the methods. Hence, the ABTS method can measure both hydrophilic and lipophilic compounds 46 . Among the Salvia species; DPPH radical scavenging IC 50 values were calculated as 9.21 ± 0.01 for methanolic extracts of S. eriophora , 38.55 ± 0.03 for root, and 93.42 ± 0.05 of leaves for the methanolic extract of S. hispanica , 86.63 ± 0.010 for ethanolic extract of S. macrochlamys , 7.05 µg/mL for methanolic S. pilifera , and 50.22 ± 1.03% of DPPH inhibition was obtained when 50 µg/mL of an ethanolic sample of S. cassia was tested 8 , 48 , 75 – 77 . Also, a study conducted by Nasirkandi et al. (2023) revealed that the IC 50 value for DPPH radical scavenging was calculated as 58.05 ± 3.31 for S. verticillata , 56.30 ± 3.31 for S. officinalis , 56.85 ± 3.91 for S. multicaulis, 58.78 ± 2.69 for S. macrochlamys , 54.62 ± 3.46 for S. candidissima , and 58.86 ± 3.91 for S. nemorosa 78 . Similarly, the ABTS radical scavenging IC 50 values were calculated as 6.03 ± 0.008 for S. eriophora , 37.15 ± 0.03 for root, and 79.58 ± 0.04 for leaves of S. hispanica , 15.75 ± 0.01 for ethanolic extract of S. macrochlamys , and 3.52 for methanolic S. pilifera 8 , 48 , 75 , 77 . These results were evaluated as S. adiyamanensis has characteristic radical scavenging properties of the genus Salvia, in terms of DPPH and ABTS, as being closer to S. eriophora and S. hispanica and ranking in higher levels of the radical scavenging list. The metal-reducing capacity of the extract was determined through three methods including CUPRAC, FRAP, and Fe 3+ -reducing assays. Both in CUPRAC and Fe 3+ -reducing assay, S. adiyamanensis yielded greater reducing capacity than synthetic Trolox. The capacity order in the assay in descending order in CUPRAC was BHA > S. Adiyamanensis > BHT > Trolox and in Fe 3+ -reducing assay BHA > BHT > S. Adiyamanensis > Trolox as being almost parallel to each other (Figs. 2 A and 2 C). On the other hand, the order in FRAP in descending order was BHT > Trolox > BHA > S. adiyamanensis (Fig. 2 B). This difference in the FRAP assay was concluded as the consequence of some drawbacks of the FRAP method, in which the assay cannot measure the antioxidant capacity of certain antioxidants accurately, which can react with ferrous ion (Fe 2+) and SH group-containing antioxidants. Besides, some polyphenols react more slowly and require longer reaction times for detection 46 . Detailed results of the antioxidant capacity test can be found in Table 1 . Higher values in Fe 3+ -metal-based methods than in Cu 2+ metal-based methods were evaluated as the result of the CUPRAC reagent being selective because it has a lower redox potential than those of Folin or ferric ion-based oxidative reagents 46 . The optimum pH for the CUPRAC assay is 7.0 close to physiological pH, simulating antioxidant action under real conditions. This method is capable of measuring both hydrophilic and lipophilic antioxidants 46 . Among the Salvia species, in CUPRAC method is almost applied the same as in this study, reducing capacity in absorbance unit was determined as 1.606 ± 0.006 for 50 µg/mL methanolic extracts of S. eriophora , 1.056 ± 0.019 for root, and 0.79 ± 0.008 of leaves for the methanolic extract of 60 µg/mL S. hispanica, 0.84 ± 0.02 for 30 µg/mL ethanolic extract of S. macrochlamys , and 1.211 ± 0.013 for 30 µg/mL methanolic S. pilifera in previous studies 8 , 48 , 75 , 77 . In FRAP, 1.944 ± 0.005 for 50 µg/mL methanolic extracts of S. eriophora , 0.847 ± 0.003 for root, and 0.587 ± 0.008 for leaves of 60 µg/mL methanolic extract of S. hispanica , 0.62 ± 0.01 for 30 µg/mL ethanolic extract of S. macrochlamys and 1.722 ± 0.008 for 30 µg/mL methanolic S. pilifera in previous studies 8 , 48 , 75 , 77 . In the Fe 3+ -reducing assay, 1.662 ± 0.002 for 50 µg/mL methanolic extracts of S. eriophora , 0.490 ± 0.003 for root, and 0.253 ± 0.004 for leaves of 60 µg/mL methanolic extract of S. hispanica , 0.88 ± 0.02 01 for 30 µg/mL ethanolic extract of S. macrochlamys and 1.762 ± 0.008 008 for 30 µg/mL methanolic S. pilifera in previous studies 8 , 48 , 75 , 77 . These results were evaluated as S. adiyamanensis has characteristic metal-reducing properties of the genus Salvia, in terms of DPPH and ABTS, as being closer to S. eriophora and S. hispanica 8 , 48 , 75 , 77 . Besides, antioxidant capacity relatedness with S. pilifera was also noticed 77 . Table 1 Antioxidant results of 45ug/mL of the ethanolic S. adiyamanensis extracts Antioxidants ABTS ·+ scavenging DPPH∙ scavenging FRAP CUPRAC Fe 3+ -reducing (IC 50) r 2 (IC 50) r 2 λ ( 593nm) r 2 λ ( 450 nm) r 2 λ ( 700 nm) r 2 Ascorbic acid 21.52 ± 8.22 0.9387 10.44 ± 5.54 0.9756 - - - - - - BHA 30.65 ± 4.89 0.9742 12.78 ± 5.43 0.9744 2.33 ± 0.01 0.9986 1.41 ± 0.07 0.9948 1.75 ± 0.04 0.9983 BHT 26.99 ± 4.18 0.9809 17.81 ± 5.43 0.9689 2.87 ± 0.06 0.9938 0.86 ± 0.02 0.9989 1.50 ± 0.08 0.9972 Trolox 43.26 ± 2.26 0.9888 8.59 ± 1.25 0.9338 2.48 ± 0.12 0.9558 0.64 ± 0.01 0.9988 0.84 ± 0.01 0.9990 S. adiyamanensis 29.50 ± 5.12 0.9714 35.40 ± 8.35 0.9005 0.75 ± 0.03 0.9844 1.27 ± 0.08 0.9916 0.87 ± 0.02 0.9921 4.2 Estimation of Enzyme Inhibition Property of Ethanolic S. adiyamanensis extract The enzyme inhibition profile of S. adiyamanensis extracts was investigated against therapeutic targets of metabolic diseases in mild to moderate stages. These enzymes were AChE, BChE, α-glycosidase, hCA I, and hCA II. Certain concentrations of the extracts were added in concentration concentration-dependent manner, IC 50 values were calculated after more than half of enzyme activity was inhibited, and the results were compared with the standard drugs that were commercially available and used in the treatment of the diseases. The data obtained from previous studies describing the role of AChE and BChE explains that the decrease in the activity of these enzymes in the central nervous system increases the concentration of acetylcholine (ACh). This improves cognitive functions and delays neurodegenerative lesions including amyloid-β (Aβ) plaques in Alzheimer's disease (AD) 79,80 . Due to unfavorable pharmacokinetic parameters of registered compounds up to now, researchers worldwide search for new AChE and BChE inhibitors for mild to moderate treatment. New compounds might be found in plants containing the following groups of compounds: alkaloids (indoles, steroids, and piperidines), phenylpropanoids (furanocoumarins, xanthones, and flavonoids), and terpenoids (diterpenes) have been reported so far with their effectiveness on the activity of AChE 81–86 . According to the result obtained from this study, S. adiyamanensis ethanolic extract inhibited the activity of AChE and BChE with 191.3 µg/mL and 8.02 µg/mL IC 50 values. While these values were 12.22 µg/mL and 8.82 µg/mL for donepezil. According to the studies reported IC 50 values for AChE and BChE were calculated as 9.91 ± 0.058 µg/mL and 5.17 ± 0.043 µg/mL for S. eriophora , 19.1 µg/mL and 13.1 µg/mL for S. hispanica , 1.622 µg/mL (AChE) for S. macrochlamys , 94.93 µg/mL and 69.05 µg/mL for S. pilifera , respectively and no cholinergic activity was determined by S. cassia 8,48,75–77 . IC 50 value difference was interpreted as activity measurement method variability as well as the solvent of extraction and species. Together with this, it can be concluded that S. adiyamanensis extracts had remarkable cholinergic activity when the results were compared with both the standard drug donepezil and previous findings reported in research with other Salvia species. Table 2 Enzyme inhibition results of S. adiyamanensis ethanolic extracts Samples AG AChE BChE hCA I hCA II IC 50 r 2 IC 50 r 2 IC 50 r 2 IC 50 r 2 IC 50 r 2 S. adiyamanensis 30.78 0.9112 191.3 0.9732 8.02 0.9963 32.68 0.9819 54.82 0.9519 Standards* 25.43 0.9656 12.22 0.9996 8.82 0.9836 55.10 0.9963 49.80 0.9957 *Standards in the table refer to acarbose for AG, donepezil for AChE and BChE, and Acetazolamide for hCA I and hCA II. α-Glycosidase is a crucial enzyme that catalyzes polysaccharides into monosaccharides in carbohydrate digestion 87 . Therefore, AGIs can decrease the D-glucose transition from intestine by the delay of complex carbohydrate breakdown, resulting in lower postprandial plasma glucose levels and control of postprandial plasma hyperglycemia. Many attempts have been made in recent years to uncover efficient AGIs from natural sources to build a physiologic functional diet or lead compound for diabetes treatment due to rich constituents including flavonoids, terpenoids, phenolics and derivatives, and tannins being biologically active 39,42,57,67,83,88–91 . Here, ethanolic S. adiyamanensis extract was subjected to α-glycosidase inhibition analysis and according to the results, the extract inhibited the α-glycosidase activity with a 30.78 µg/mL IC 50 value. In contrast, this value was 25.43 µg/mL for the standard diabetes drug, acarbose. According to the previous studies, α-glycosidase was inhibited with IC 50 values 5.54 ± 0.050 µg/mL S. eriophora , 0.530 µg/mL for S. macrochlamys , and 23.28 µg/mL for S. pilifera 48,75,77 . Shojaeifard et. al (2023), have been tested fifty different types of Salvia species against α-glycosidase enzymes, and they concluded that S. multicaulis, S. santolinifolia, S. dracocephaloides , and S. eremophila were stronger inhibitors than acarbose with IC 50 values in the range of 26.23–92.35 µg/mL 87 . Based on these findings, S. adiyamenensis was concluded as S. adiyamanensis has powerful potential to be a natural α-glycosidase inhibitor. According to the study conducted in 2025, S. aucheri, S. candidissima, S. divaricata, S. virgata, S. multicaulis, S. palestine, S. trichoclada, and S. cerino-pruinosa have been tested against various metabolic enzymes including α-glycosidase and they have determined that alcoholic extracts of all species have been yielded remarkable AG inhibition property which can be accepted as better than that acarbose 92 . CAs have a regulatory role in many physiological processes such as gluconeogenesis, ureagenesis, fluid secretion, acid/base balance, gastric acid production, and transport of CO 2 from tissues to the lungs (in the form of bicarbonate) through the blood 70,73,93 . The critical importance of CAs in the regulation of these processes, they play a major role in the pathophysiology of various diseases like hemolytic anemia, glaucoma, renal tubular acidosis, osteoporosis, neuropathic pain, colorectal cancer, etc. As a result, carbonic anhydrase inhibitors (CAIs) find therapeutic applications for the treatment of various clinical disorders 39,55,72–74,82,83,85,94 . There sixteen isoforms of CAs have been identified and each of them has a different role in the treatment of various diseases 39,55,73 . For instance, while CA I and CA II are linked to hemolytic anemia, CA II is also associated with glaucoma, epilepsy, edema, and altitude sickness 94–96 . A wide range of diseases from cancer to diabetes, have been linked to different CA isoforms 94 . Therefore, it is important to identify and determine novel CAIs. Here, ethanolic S. adiyamanensis extracts were tested against hCA I and hCA II enzymes to evaluate its potential as a novel CAI. According to the results, S. adiyamanensis extract inhibited the activity of hCA I and hCA II enzymes with 32.68 µg/mL and 54.82 µg/mL IC 50 values, while these values were 55.10 µg/mL and 49.80 µg/mL for standard drug, acetazolamide. Based on the literature findings, hCA I and hCA II enzymes were inhibited with 39.2 µg/mL and 38.5 µg/mL IC 50 values by S. hispanica , 3097.0 ± 300.6 µg/mL for S. miltiorrhiza 97 . Results from S. hispanica hCA inhibition test results from the literature were quite similar to those obtained in this study 8 . Details of enzyme inhibition study can be found in Table 2. 4.3. Phytochemical Analysis of Ethanolic S. adiyamanensis Extract Phytochemical analysis of the ethanolic S. adiyamanensis extract was performed through spectrophotometric TFC/TPC and chromatographic LC-MS/MS methods. The TPC of the extract was 543 mg GAE /g of extract and the TFC of the extract was 122.17 ± 0.12 mg QE/g of the extract have been determined. In addition, the extraction yield was calculated as 28% with methanol extraction. The TPC and the TFC values were calculated as 36.35 mg GAE per gram extract and 68.70 QE/g extracts for S. pilifera , 39.87 ± 1.12 QE/g extracts, and 27.95 ± 0.36 QE/g extracts for S. cassia , 150.1 ± 1.1 mg GAE/g and 38.9 ± 3.1 mg QE/g for S. macrochlamys , 62.35 ± 0.09 mg GAE/g and 46.93 ± 0.05 mg QE/g for S. hispanica , 102.00 mg GAE/g and 22.44 ± 0.49 mg QE/g for S. aucheri, 66.51 ± 1.69 mg GAE/g and 23.23 ± 0.37 mg QE/g S. candidissima , 54.83 ± 1.29 mg GAE/g and 35.97 ± 0.39 mg QE/g for S. divaricate, 96.93 ± 3.06 mg GAE/g and 25.72 ± 0.07 mg QE/g for S. virgata , 92.16 ± 4.19 mg GAE/g and 34.89 ± 0.28 mg QE/g S. multicaulis , 50.13 ± 0.57 GAE/g and 37.00 ± 0.08 mg QE/g for S. palestina , 105.13 ± 12.10 mg GAE/g and 32.24 ± 0.51 mg QE/g for S. trichoclada , 124.15 ± 0.17 GAE/g and 35.93 ± 0.57 mg QE/g for S. cerinopruinosa , respectively 8,92 . These results concluded that Salvia phenolic and flavonoid content signs were detected in the novel Turkish Sage content. Tablo 3. Quantitative LC-MS/MS Results of ethanolic S. adiyamanensis extract: LOD; Limit of Detection Compound Acquisition Time Response Concentration (ng/mL) 1 Quinic Acid 2.359 959 335.7590 2 Fumaric Acid 4.015 23 <LOD 3 Gallic Acid 5.606 11 <LOD 4 Pyrogallol 6.696 2 <LOD 5 Cyanidin-3-o-glucoside 10.597 11 26.0745 6 Chlorogenic Acid 10.599 89534 3366.8520 7 Keracyanin Chloride 10.654 10 8.6532 8 Peonidin-3-o-glucoside 10.959 4 <LOD 9 Catechin 10.978 16 <LOD 10 4-OH-Benzoic Acid 11.102 6265 345.2810 11 Caffeic Acid 11.375 64687 1087.8426 12 Epicatechin 11.413 8 <LOD 13 Epigallocatechin Gallate 11.510 8 <LOD 14 Vanillic Acid 11.579 20 <LOD 15 Vitexin 11.598 4049 5.4587 16 Naringin 11.871 793 40.6222 17 Syringic Acid 11.895 16 <LOD 18 Hesperidin 11.929 3004 238.0012 19 Ellagic Acid 11.992 71 <LOD 20 p-Coumaric Acid 12.246 3910 40,1215 21 Taxifolin 12.267 4328 <LOD 22 Sinapic Acid 12.388 5 <LOD 23 Rosmarinic Acid 12.468 1226526 301734.0851 24 Ferulic Acid 12.548 40 <LOD 25 Vanillin 12.623 0 <LOD 26 Myricetin 12.889 14 <LOD 27 Resveratrol 13.185 0 <LOD 28 Luteolin 13.327 295703 2465.8651 29 Quercetin 13.427 72880 1703.5567 30 Apigenin 13.879 126078 1412.7408 31 Naringenin 13.907 6929 80.4182 32 Isorhamnetin 14.194 17057 19.0130 33 Galangin 15.183 75 <LOD 34 Curcumin 15.454 23 <LOD 35 Chrysin 15.489 25 <LOD LC-MS/MS analysis for ethanolic extract of S. adiyamanensis was performed against a total of thirty-five compounds including organic acid, phenolics, and flavonoids 62 . According to the results, sixteen different compounds were identified and six of them were determined in ppm level including in descending order as rosmarinic acid, chlorogenic acid, luteolin, quercetin, apigenin, and caffeic acid. Relatively lower amounts of other phenolics and organic acids such as quinic acid, cyanidin-3-o-glucoside, keracyanin chloride, 4-OH-benzoic acid, vitexin, naringin, hesperidin, p-coumaric acid, naringenin, and isorhamnetin. Although the taxifolin response has been determined, the metabolite could not be determined due to its amount being under the limit of detection. The chromatogram and the quantitative results of LC-MS/MS analysis can be found in Fig. 3. and Table 3, respectively. In a study conducted to analyze phenolics in eight different types of Salvia species against quite a wide range of standard phenolics; Malic acid, isocitric acid, citric acid rosmarinic acid, Danshensu, caffeic acid, sagerinic acid isomer, oxo-dihydroxy‐octadecenoic acid, and trihydroxy‐octadecenoic acid were detected in all Salvia species including S. aucheri, S. candidissima, S. divaricate, S. virgata, S. multicaulis, S. palestina, S. trichoclada and S. cerinopruinosa 26 . Fumaric acid, quercetagetin-3,6-dimethyl ether, and salvigenin have been majorly detected in S. pilifera methanolic extract; rosmarinic acid, syringic acid, luteolin, apigenin, nepedin, hispidulin, penduletin, acacetin, and hederagenin in ethanolic S. macrochlamys extract; salvigenin and fumaric acid in methanoli c S. eriophora; rosmarinic acid, quinic acid, and caffeic acid in S. hispanica extracts; luteolin and rutin in S. fruticosa , rosmarinic acid in S. officinalis 8,14,48,75,77,98 . Quercetin is a well-known flavonoid with a wide range of biological activity, however, in recent years, its effects on the digestion of lipids and carbohydrates have been extremely popular to be a potential natural candidate as an antidiabetic agent 99–101 . As previously reported, the antioxidant capacity of the Salvia extracts is mostly related to its rosmarinic acid content, an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid, and is a natural polyphenol carboxylic acid, an ester of caffeic and 3,4-dihydroxyphenyllactic acids, a good potential source of antioxidants for food protection and pharmaceutical applications 67 . In a study investigating, the effect of rosmarinic acid against CA IX and XII isoenzymes, AChE, BChE, lactoperoxidase (LPO), and glutathione S-transferase (GST) were evaluated and it has been reported that rosmarinic acid showed low micromolar inhibition against both CA isoenzymes (CA IX and XII) and LPO, nanomolar inhibition against GST and picomolar inhibition against ACE and BChE. The results showed that rosmarinic acid moderately inhibited both CA isoenzymes, but effectively inhibited GST, ACE, and BChE 102 . The second abundant metabolite was chlorogenic acid, which is a member of the chlorogenic acid family (CGA) abundant in dietary phenolic acid compounds in plants, conjugating the hydroxy group of quinic acid and the carboxyl group of caffeic acid as the parent structure. The CGA family has shown multiple protective effects on mitigating many chronic inflammatory and age-related disorders through exerting the central actions of anti-inflammation, antioxidation, and metabolic homeostasis modulation 103,104 . In a study that was conducted to investigate enzyme inhibition properties of chlorogenic acid, IC 50 values over α-amylase and α-glucosidase were determined as 9.10 µg/mL and 9.24 µg/mL as being remarkably significant 105 . CONCLUSION The ethanolic extract of S. adiyamanensis exhibited significant antioxidant and enzyme inhibitory properties, positioning it as a promising natural source for therapeutic applications. The extract demonstrated strong DPPH and ABTS radical scavenging capacities, comparable to well-known commercial natural and synthetic antioxidants such as ascorbic acid, BHA, BHT, and Trolox. Additionally, its metal-reducing capacity was notably high, surpassing Trolox in certain assays like CUPRAC and Fe 3+ -reducing assays, further reinforcing its potential as an effective antioxidant. The enzyme inhibition profile also highlighted the medicinal value of S. adiyamanensis , with remarkably high inhibitory effects against key therapeutic targets related to metabolic diseases. Specifically, the extract showed potent inhibition of AChE and BChE, suggesting its potential in managing neurodegenerative conditions like Alzheimer’s disease. Furthermore, its α-glucosidase inhibition activity supports its application in managing diabetes, as it demonstrates comparable efficacy to acarbose. The extract’s inhibition of hCA I and hCA II enzymes further indicates its relevance in treating conditions like glaucoma and hemolytic anemia 55 , 72 , 73 , 96 , 106 . Phytochemical analysis revealed a rich presence of bioactive compounds, particularly phenolic acids, and flavonoids, including rosmarinic acid, chlorogenic acid, luteolin, quercetin, and caffeic acid, which are likely responsible for the observed biological activities 67 , 99 – 104 , 107 – 110 . These findings align S. adiyamanensis with other Salvia species known for their antioxidant and medicinal properties 1 , 2 , 5 , 6 , 8 , 11 – 18 , 21 , 26 , 76 , 111 – 114 . Overall, Salvia a diyamanensis shows substantial potential for further development into a functional natural product for the prevention and management of various diseases, particularly neurodegenerative disorders, diabetes, and conditions involving carbonic anhydrase enzymes. Its diverse pharmacological activities and its phytochemical richness warrant additional research to fully explore its therapeutic potential. While the Salvia genus is known for its medicinal and therapeutic properties, some species within this genus have been reported to exhibit varying degrees of toxicity, particularly when consumed in large quantities or improperly prepared 115 , 116 . Certain Salvia species, such as S. divinorum , contain psychoactive compounds like salvinorin A, which can induce intense hallucinogenic effects and may pose risks to mental health and well-being when used recreationally 117 . Other species, depending on their chemical composition, may contain compounds that could be toxic to specific organs or systems if ingested inappropriately 115 , 116 . However, many Salvia species, have not shown significant toxicity in the doses typically used for medicinal purposes, with studies indicating a relatively safe profile when consumed in moderate amounts or when used topically 11 , 16 , 19 , 21 , 111 . Despite this, further research into the toxicity and safety of various Salvia species is necessary to better understand their potential risks and to ensure their safe and effective use in traditional and modern therapeutic applications. Declarations Data availability The authors declare that the data supporting the findings of this study are available within the paper. Acknowledgments Ilhami Gulcin is a member Turkish Academy of Sciences (TÜBA). He would liken to extend his sincere appreciation to the TÜBA for their financial support. Author contributions A.Z.T. carried out the experiment, methodology, and investigation. K.A. carried out the experiment, methodology, and investigation. İ.G. designed the study, analyzed data, supervised the experiment and prepared the manuscript. All the authors gave their consent for the publication. Competing interests Te author declares no competing interests. References Wu, Y. B. et al. 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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-6213034","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":438844413,"identity":"3d61bd55-cb6d-4a76-bd64-ccaa00069423","order_by":0,"name":"Ahmet Zafer TEL","email":"","orcid":"","institution":"Atatürk University","correspondingAuthor":false,"prefix":"","firstName":"Ahmet","middleName":"Zafer","lastName":"TEL","suffix":""},{"id":438844414,"identity":"9b416751-5ebe-4b23-a035-f707a5751555","order_by":1,"name":"Kubra ASLAN","email":"","orcid":"","institution":"Atatürk University","correspondingAuthor":false,"prefix":"","firstName":"Kubra","middleName":"","lastName":"ASLAN","suffix":""},{"id":438844417,"identity":"6d995872-0d79-457c-97cb-74b410ad87f8","order_by":2,"name":"Ilhami GULCIN","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIiWNgGAWjYBACNgYGxgMMBgxyEK4BEB8grIUBpMUYzIJqYWwgZBPI2MQGNgQXvxY+/jUGB34U3Envn9/8TLqggEGO70YC++MKfA6TeGNwsMfgWe6MY2xm0jOALpS8kcDYeAavljMGhxkMDuc2HGMwk+YxYEjcANKCz2UwLenyx9i/gbTUE9bC3wPWkmBwjAdsS4IBYVvYCoB+OWy48VhOsTWPgYThzDMPG2fi0yLff3jjgx9/DsvLHT6+8TbPHxt5vuPJBz7i08IgkYDKBWJCMcl/AL/8KBgFo2AUjAIGACpnTcp8llgSAAAAAElFTkSuQmCC","orcid":"","institution":"Atatürk University","correspondingAuthor":true,"prefix":"","firstName":"Ilhami","middleName":"","lastName":"GULCIN","suffix":""}],"badges":[],"createdAt":"2025-03-12 14:38:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6213034/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6213034/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":80336178,"identity":"0bc7b736-da9b-455d-8933-14ee3bc5bed9","added_by":"auto","created_at":"2025-04-10 16:26:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":130833,"visible":true,"origin":"","legend":"\u003cp\u003eRadical Scavenging Property of Turkish Sage a) DPPH Radical Scavenging results b) ABTS Radical Scavenging Results\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6213034/v1/a73dae7f6256122328cf7e7c.png"},{"id":80336181,"identity":"0443a201-1871-4f62-8831-ca26f42c6598","added_by":"auto","created_at":"2025-04-10 16:26:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":226856,"visible":true,"origin":"","legend":"\u003cp\u003eMetal Reducing Capacity Test Results of Turkish Sage A) FRAP Results, B) Fe\u003csup\u003e3+\u003c/sup\u003e-reducing Results, C) CUPRAC Results\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6213034/v1/7a0ac41fd8d1876d84e27c0a.png"},{"id":80336191,"identity":"9231201a-6d63-4467-b633-f74495ffbbd4","added_by":"auto","created_at":"2025-04-10 16:26:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":232382,"visible":true,"origin":"","legend":"\u003cp\u003eLC-MS/MS chromatogram of the ethanolic S. adiyamanensis extract (Inset; Expanded multiple reaction monitoring chromatograms) Numbers of chromatograms and peaks in red and yellow labels refer to Table 3)\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6213034/v1/87c43bc6df1eb4d25207d398.png"},{"id":82515842,"identity":"1f15885f-38e9-4eb0-a2f5-975d49870e7b","added_by":"auto","created_at":"2025-05-12 11:39:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2212088,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6213034/v1/89087a83-c1fe-4e48-876e-e98032cc0ee0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Phytochemical Analysis, Antioxidant, Anticholinergic, Antidiabetic, and Antiglaucoma Potentials of Sage (Salvia adiyamanensis)","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003e\u003cem\u003eSalvia\u003c/em\u003e, also known as sage, species are a subgroup of the Lamiaceae family that grows in temperate and warmer regions including the Mediterranean, Central Asia, the Pacific Islands, tropical Africa, and America \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. According to the Plant of World Online database, 1024 species are accepted worldwide. Common or medicinal sage (\u003cem\u003eS. officinalis\u003c/em\u003e), steppe sage (\u003cem\u003eS. stepposa)\u003c/em\u003e, clary or musk sage (\u003cem\u003eS. sclarea)\u003c/em\u003e, desert sage (\u003cem\u003eS. deserta\u003c/em\u003e), woodland sage, blue sage or wild sage (\u003cem\u003eS. nemorosa)\u003c/em\u003e, lilac sage (\u003cem\u003eS. verticillata)\u003c/em\u003e, Mediterranean sage or African sage \u003cem\u003eS. aethiopis\u003c/em\u003e, Spanish sage (\u003cem\u003eS. lavandulaefolia)\u003c/em\u003e, Lebanese sage \u003cem\u003e(S. libanotica)\u003c/em\u003e and Chinese sage \u003cem\u003e(S. miltiorrhiza)\u003c/em\u003e are among the \u003cem\u003esalvia\u003c/em\u003e types that are distinguished with their valuable benefits to the human as a flavoring agent in food, cosmetic and traditional medicine \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. \u003cem\u003eS. officinalis\u003c/em\u003e, \u003cem\u003eS. lavandulaefolia\u003c/em\u003e, and \u003cem\u003eS. miltiorrhiza\u003c/em\u003e have been used for centuries as restoratives for lost or declining mental functions such as in Alzheimer\u0026rsquo;s disease (AD)\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. \u003cem\u003eS. libanotica\u003c/em\u003e has been used for many years to cure diseases such as abdominal pains, headaches, indigestion, and heart disorders \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. \u003cem\u003eS. officinalis\u003c/em\u003e has been traditionally used to treat menopausal syndromes, for that matter, once-daily application of the fresh sage extract evaluated as clinically valuable in terms of safety, efficacy, and tolerability in the treatment of menopausal symptoms\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Danshen is an \u003cem\u003eS. miltiorrhiza-\u003c/em\u003eoriginated medicinal herb that possesses broad cardiovascular and cerebrovascular protective actions and has been used in Asian countries for many centuries\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. In addition to these, a wide range of antimicrobial, antioxidant activity, anti-inflammatory, antinociceptive, antimutagenic, anticancer, anti-diarrheal, cholesterol-lowering, and anti-diabetic activities of different sage have been reported so far\u003csup\u003e\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe importance of sage is not limited to its medicinal use but also its use in food and cosmetics. Due to the rich antioxidant and antimicrobial metabolite content, much research has focused on the integration of \u003cem\u003eSalvia\u003c/em\u003e into food preservation including processed meat and milk from peroxidation and microbial growth\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Besides, antimicrobial activity is one of the most cited bioactivities of \u003cem\u003eSalvia\u003c/em\u003e essential oils (EOs), including against bacteria and fungi; e.g., \u003cem\u003eS. amplexicaulis, S. officinalis\u003c/em\u003e, therefore, application of \u003cem\u003esalvia\u003c/em\u003e EOs and extracts to cosmetic formulation is highly demanded\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Current studies have been focusing on enzyme inhibitory properties against the enzymes including collagenase and elastase with remarkable effects for derma cosmetic applications, besides, some acne and wound healing activities in both \u003cem\u003ein vivo\u003c/em\u003e and \u003cem\u003ein vitro\u003c/em\u003e studies have been reported\u003csup\u003e\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Different formulations for targeted delivery, and more eligible physicochemical properties including solubility, swelling, and surface/volume ratios have been developed by researchers to increase the effective usage of these versatile plant extracts\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe published literature reports that lipophilic constituents as well as hydrophilic constituents contribute to the biological actions of \u003cem\u003esalvia\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Phytochemical analyses made today revealed that the main constituents of \u003cem\u003esalvia\u003c/em\u003e species are diterpenes being the largest group and the others being less abundant are the monoterpenes, sesquiterpenes, sesterterpenes, triterpenes, steroids, and phenols. Among diterpenes, abietane diterpenes are the largest group of known \u003cem\u003eSalvia\u003c/em\u003e diterpenes. In recent years, much effort has been invested to identify water-soluble \u003cem\u003eSalvia\u003c/em\u003e constituents, such as phenolic acids and flavonoids\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. The main phenolic of \u003cem\u003eSalvia\u003c/em\u003e is caffeic acid which plays a central role in synthesizing the simple monomers into oligomers, followed by caffeic acid and 3-(3,4-dihydroxyphenyl) lactic acid, ferulic acid, isoferulic acid, chlorogenic acid. The majority of antioxidant activity and therapeutic activity of \u003cem\u003esalvia\u003c/em\u003e species originates from rosmarinic acid, dimer, and salvianolic acid B, a tetramer of caffeic acid\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. The most representative flavonoids are flavones of apigenin and luteolin and their corresponding 6-hydroxylated derivatives, flavonols, and their glycosides. The flavonoids luteolin, quercetin, salvigenin identified in several \u003cem\u003eSalvia\u003c/em\u003e species\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe diverse array of bioactive compounds present in plants has long attracted the attention of the scientific community due to their potential beneficial effects on human health. Among these compounds, antioxidants-a group of molecules capable of inhibiting or delaying oxidative processes-have emerged as key players in the prevention and management of various chronic diseases\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e .Research over the past several decades has increasingly focused on plant-derived antioxidants, as numerous studies have demonstrated their ability to neutralize free radicals and reduce oxidative stress, which is implicated in the pathogenesis of conditions such as cardiovascular disease, cancer, and neurodegenerative disorders\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePlants synthesize an impressive range of antioxidant compounds as part of their secondary metabolism. These compounds include polyphenols, flavonoids, carotenoids, vitamins, and other phytochemicals that not only contribute to the plant\u0026rsquo;s own defense mechanisms against environmental stressors but also confer significant health benefits when consumed\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Polyphenols, for example, are well recognized for their potent free radical and reactive oxygen species (ROS) scavenging abilities and are abundant in fruits, vegetables, teas, and wines. Flavonoids, a major subclass of polyphenols, have been extensively studied for their anti-inflammatory, anti-carcinogenic, and cardioprotective properties\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e .\u003c/p\u003e \u003cp\u003eAdvancements in analytical techniques have significantly enhanced our ability to assess the antioxidant capacity of plant extracts and isolated compounds. Standard assays such as the ferric reducing ability, and radical scavenging assay provide quantitative measures of antioxidant potential\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. These methods have been pivotal in establishing a link between in vitro antioxidant activities and the potential in vivo effects of plant-based compounds. However, a major challenge remains in correlating these assay results with the complex biological processes in humans. Factors such as bioavailability, metabolism, and the synergistic interactions among multiple antioxidants in the diet complicate the translation of laboratory findings to real-world health outcomes\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eEpidemiological studies consistently underscore the health benefits of diets rich in plant-based foods. Populations that consume a high intake of fruits, vegetables, nuts, and whole grains typically exhibit lower incidences of chronic diseases, a phenomenon partly attributed to the high levels of naturally occurring antioxidants\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Numerous clinical and experimental investigations have revealed that these bioactive compounds not only mitigate oxidative damage but also modulate key cellular signaling pathways, influence gene expression, and even induce apoptosis in malignant cells. Such findings suggest that the protective effects of plant antioxidants extend beyond mere free radical scavenging, offering a multifaceted approach to disease prevention and health promotion\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. Moreover, the application of plant-derived antioxidants is not limited solely to health and nutrition. In the food industry, these natural compounds are increasingly employed as alternatives to synthetic preservatives, thereby enhancing the shelf life and safety of various products without the adverse effects sometimes associated with chemical additives\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn summary, the exploration of plant content and its antioxidant properties represents a vibrant and essential field of research. The growing body of literature highlights the significant role that plant antioxidants play in neutralizing free radicals and mitigating oxidative stress, ultimately contributing to the prevention of a wide range of chronic diseases\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e.While in vitro studies and epidemiological data provide strong evidence for these benefits, future research must aim to elucidate the precise mechanisms by which these compounds exert their effects in vivo. A deeper understanding of these processes will not only validate the health claims associated with antioxidant-rich diets but also pave the way for the development of novel therapeutic strategies derived from nature\u0026rsquo;s own pharmacopeia. This comprehensive view reinforces the importance of dietary diversity and underscores the potential of plant-based interventions in promoting overall health and longevity\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAcetylcholinesterase (AChE) is a crucial enzyme responsible for terminating synaptic transmission by catalyzing the rapid hydrolysis of the neurotransmitter acetylcholine (ACh)\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. Inhibition of AChE results in elevated levels of acetylcholine at synapses, thereby enhancing cholinergic neurotransmission. This pharmacological strategy is particularly significant in the treatment of neurodegenerative disorders such as Alzheimer\u0026rsquo;s disease (AD), where drugs like donepezil, rivastigmine, and galantamine serve as reversible AChE inhibitors to improve cognitive function and memory\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e. Additionally, AChE inhibitors are employed in the management of conditions like myasthenia gravis and as antidotes against organophosphate poisoning. The development and optimization of these inhibitors have been driven by detailed studies of the enzyme\u0026rsquo;s structure, kinetics, and role in neural function\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Ongoing investigations continue to refine these agents, aiming to maximize clinical benefits while minimizing adverse effects\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eα-Glycosidase is an enzyme that plays a critical role in carbohydrate digestion by hydrolyzing complex carbohydrates and disaccharides into simple sugars in the gastrointestinal tract\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e,\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e. The regulation of α-glycosidase activity is particularly important in diabetes management, as excessive carbohydrate digestion leads to rapid glucose absorption, resulting in postprandial hyperglycemia. Inhibiting α-glycosidase with drugs such as acarbose and miglitol has become an effective therapeutic strategy for controlling blood sugar levels in individuals with type-2 diabetes (T2DM)\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e,\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e. These inhibitors slow the breakdown of carbohydrates, thereby reducing the post-meal rise in blood glucose. Several studies have highlighted the beneficial effects of α-glycosidase inhibitors in improving glycemic control, decreasing insulin resistance, and even possibly delaying the progression of diabetes complications\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCarbonic anhydrases (CAs) are metalloenzymes that catalyze the reversible conversion of carbon dioxide and water to bicarbonate (HCO\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e\u0026minus;\u003c/sup\u003e) and a proton\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e. In the context of glaucoma, the most relevant form is carbonic anhydrase II (CA II), which plays a critical role in the regulation of aqueous humor production in the eye\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e. Inhibition of CA reduces the production of HCO\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e\u0026minus;\u003c/sup\u003e ions, leading to a decrease in aqueous humor secretion and consequently lowering intraocular pressure (IOP). This reduction in IOP helps manage glaucoma, particularly primary open-angle glaucoma, by preventing optic nerve damage caused by elevated pressure\u003csup\u003e\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e,\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e. Two commonly used CA inhibitors (CAIs), acetazolamide and dorzolamide, have been shown to effectively reduce IOP and are commonly employed in both oral and topical forms as adjunctive therapies\u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e,\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u003c/sup\u003e. However, long-term use of CAIs may be associated with side effects such as metabolic acidosis and kidney stones. Ongoing research continues to focus on improving the efficacy and minimizing the adverse effects of CA inhibitors in the treatment of glaucoma\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the present study, it was aimed to explore the phytochemistry and biological activity of a novel species of \u003cem\u003eSalvia\u003c/em\u003e (\u003cem\u003eSalvia adiyamanensis\u003c/em\u003e İl\u0026ccedil;im \u0026amp; Tel \u003cem\u003esp. nova\u003c/em\u003e) collected from the Adiyaman province in Southeastern Anatolia, Turkey, which is considered to be the center of \u003cem\u003eSalvia\u003c/em\u003e diversity\u003csup\u003e\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e. This new species is related to \u003cem\u003eS. cassia\u003c/em\u003e which is restricted to Amanos mountains, particularly south and south-east of Turkey \u003csup\u003e\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e .By analyzing the chemical composition through chromatographic and spectroscopic methods and examining the biological properties of ethanolic extracts from this plant, we sought to uncover its potential industrial applications and reveal the relativeness to the other members of the \u003cem\u003eSalvia\u003c/em\u003e genus. Our research focused on several key biological activities, including antioxidant, anti-cholinergic, antidiabetic, and antiglaucoma effects. Through these investigations, we aimed to shed light on the plant\u0026rsquo;s phytochemical profile and assess its viability as a source of natural bioactive compounds with promising health benefits.\u003c/p\u003e"},{"header":"MATERIAL AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Plant Material\u0026amp;Chemicals\u003c/h2\u003e \u003cp\u003e \u003cem\u003eSalvia adiyamanensis\u003c/em\u003e İl\u0026ccedil;im \u0026amp; Tel collection coordinates are 37˚ 53\u0026rsquo; 27 N- 38˚ 17\u0026rsquo; 46 E. Adıyaman to Malatya road 17.km, between Rezip-Semikhan villages. Habitat was defined as Rocky steppe with 1070 m altitude. The plant was classified as a local endemic and the International Union for Conservation of Nature category was determined as Critically endangered\u003csup\u003e\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e. The species was registered to the Adıyaman University Herbarium with fixture number 1395 by Plant Taxonomist Prof. Dr. Ahmet Zafer TEL.\u003c/p\u003e \u003cp\u003eStandard phenolics used in LC/MS-MS calibration and validation were purchased from Sigma Aldrich GmbH (Steinheim, Germany). Acetylcholinesterase (AChE) from \u003cem\u003eElectrophorus electricus\u003c/em\u003e (electric eel) Type VI-S lyophilized powder 200\u0026ndash;1000 U/mg protein, Butyrylcholinesterase (BChE) from equine serum lyophilized powder\u0026thinsp;\u0026ge;\u0026thinsp;900 units/mg protein, Alpha-Glucosidase Type I From Bakers Yeast 100 UN were purchased Sigma Aldrich GmbH. Human carbonic anhydrase I and II isoenzymes (hCAI ve hCA II) were isolated from human erythrocytes through hemolysis, purified by affinity column chromatography, and characterized by SDS-PAGE as previously applied\u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e,\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u003c/sup\u003e. Acetylthiocholine iodide 99.0% (AT), Butyrylthiocholine iodide (BT)\u0026thinsp;\u0026ge;\u0026thinsp;98%, 5,5'-Dithiobis (2-Nitrobenzoic Acid), 4-Nitrophenyl β-D-glucopyranoside (p-NPG)\u0026thinsp;\u0026ge;\u0026thinsp;98% (TLC), 4-Nitrophenyl acetate (p-NFA)\u0026thinsp;\u0026ge;\u0026thinsp;99.0% (GC) were purchased from Sigma Aldrich. Other used but not mentioned chemicals are of analytical grade.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Preparation of S. \u003cem\u003eadiyamanensis\u003c/em\u003e ethanol extracts\u003c/h2\u003e \u003cp\u003eEthanol extracts of S. adiyamanensis were prepared by weighing 25 g of dried aerial parts of the plant. Then, 100 mL of ethanol was added to the milled plant material in a beaker and the sample was mixed for 5 hours for the preparation of ethanol extracts. Ethanol was removed from the extracts by rotary evaporator. The overall extraction yields were calculated by dividing the remaining extracts by the quantity of the starting dried plant. 100 mg of dry extracts were separated for LC-MS/MS analysis, and an ethanol and DMSO solution of extracts concentrated between 15\u0026ndash;45 \u0026micro;g/mL was prepared for further antioxidant capacity, and enzyme inhibition tests.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Phytochemical Analysis of The Extracts\u003c/h2\u003e \u003c/div\u003e\u003ch3\u003e2.3.1. Total flavonoid and total phenol content of \u003cem\u003eS. adiyamanensis\u003c/em\u003e extracts\u003c/h3\u003e\n\u003cp\u003eThe samples\u0026apos; total flavone and flavonol contents were determined by analyzing through the Al(NO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e colorimetric method\u003csup\u003e\u003cspan lang=\"TR\"\u003e57\u003c/span\u003e\u003c/sup\u003e. 1 mg of extracts in 0.5 mL ethanol was mixed with 1.5 mL of 95% methanol. Then, 0.5 mL of 1.0 M potassium acetate, 2.3 ml of distilled water, and 1.5 mL of 10% Al (NO\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e3\u003c/sub\u003e were added to the reaction mixture, and the samples were incubated at 25\u003csup\u003eo\u003c/sup\u003eC for 40 min after vigorously shaking. Nitrates in the method serve as nitrating agents for romatic vicinal diols to produce a flavonoid-nitroxyl derivative that can be measured spectrophotometrically\u003csup\u003e46,58,59\u003c/sup\u003e. Absorbances of each reaction at 415 nm were recorded, and the results were expressed as \u0026micro;g quercetin equivalents (QE)/mg of \u003cem\u003eS. adiyamanensis\u003c/em\u003e extract. A standard curve of quercetin was obtained within a concentration range of 1-500 \u0026micro;g/mL. The total phenolic content of 1 mg plant extract was determined by the Folin-Ciocalteu (FC) method applied by Karagecili et al. (2023a) splitting the volumes of each component by half\u003csup\u003e57,59\u003c/sup\u003e. the FC assay is based on the reduction of a yellow phosphotungstate\u0026ndash;phosphomolybdate complex by antioxidants (reductants) to a blue chromogen that can be measured spectrophotometrically at 760 nm\u003csup\u003e\u003cspan lang=\"TR\"\u003e59,60\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003ch3\u003e2.3.2. Screening of Polyphenolics of \u003cem\u003eS. adiyamanensis\u003c/em\u003e Extracts by LC-MS/MS\u003c/h3\u003e\n\u003cp\u003eThirty-five phenolic compounds were quantified in total by liquid chromatography (Agilent Technologies 1290 Infinity UHPLC chromatography, Palo Alto, USA) followed by electrospray ionization (ESI) MS-MS (Agilent 6460 mass spectrometer, Palo Alto, USA). UHPLC-ESI-MS/MS data were acquired and processed by MassHunter Qualitative Analysis B07 and MassHunter Quantitative Analysis B07 software (Agilent, USA). The LC-MS/MS method was applied as previously reported and adopted for dried samples of ethanolic \u003cem\u003eS. adiyamanensis\u003c/em\u003e\u003csup\u003e\u003cspan lang=\"TR\"\u003e61,62\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003ch2\u003e2.4. Determination of Antioxidant Properties of \u003cem\u003eS. adiyamanensis\u003c/em\u003e\u003c/h2\u003e\n\u003ch3\u003e2.4.1. DPPH and ABTS Radical Scavenging Activity\u003c/h3\u003e\n\u003cp\u003eDPPH Radical scavenging activity determination assay was performed as previously applied\u003csup\u003e\u003cspan lang=\"TR\"\u003e57,63\u003c/span\u003e\u003c/sup\u003e. An ethanol solution of 0.5 mM DPPH was prepared and incubated in the dark by mixing overnight for pre-radicalization. Then, 0.5 mL of DPPH and 0.5 mL of the \u003cem\u003eS. adiyamanensis\u0026nbsp;\u003c/em\u003esamples in ethanol (15-45 \u0026micro;g/mL) were mixed and incubated at 30\u003csup\u003eo\u003c/sup\u003eC for 30 minutes. The sample contains DPPH and ethanol used as a control reaction. The absorbances of each sample were recorded at 517 nm and a decrease in absorbance of the control reaction was accepted as a radical scavenging property\u003csup\u003e\u003cspan lang=\"TR\"\u003e59,63,64\u003c/span\u003e\u003c/sup\u003e. ABTS radical scavenging was performed based on the bleaching ability of different concentrations of the extracts\u003csup\u003e57,65\u003c/sup\u003e. Pre-radicalize ABTS radicals were obtained by mixing an equal volume of 2.45 mM potassium-thiosulphate and 2 mM ABTS for 6 hours in the dark. Then, the absorbance of ABTS radical solution at 734 nm was maintained at about 1.0 by diluting the ABTS reagent with 0.1 M, pH 7.4 phosphate buffer solution (PBS). The assay was performed by incubating 1.0 mL of ABTS solution and 3.0 mL of the samples (15-45 \u0026micro;g/mL) in 0.1 M PBS, pH 7.4 for 30 minutes. The bleaching ability of the samples was measured by the decrease in absorbance at 734 nm. The sample contains ABTS and PBS used as a control reaction. A decrease in absorbance of the control reaction is accepted as a radical scavenging property. DPPH and ABTS assays were also performed for reference antioxidants, including ascorbic acid, BHA, BHT, \u0026alpha;-tocopherol, and trolox. Each test was performed in triplicate. Percentages of the inhibition were calculated by using the formula;\u003c/p\u003e\n\u003cp\u003e% DPPH/ABTS Scavenging = 100-(Sample\u0026rsquo; absorbances/Control\u0026rsquo; absorbance) x100\u003c/p\u003e\n\u003ch3\u003e2.4.2. Reducing Antioxidant Capacity Test\u003c/h3\u003e\n\u003cp\u003eThe ability of \u003cem\u003eS. adiyamanensis\u003c/em\u003e extracts to reduce metal complexes was investigated with three different methods which are performed in triplicate for each sample and compared with the positive controls, BHA, BHT, alpha-tocopherol, and trolox.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFe\u003csup\u003e+3\u003c/sup\u003e -Reducing assay\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e 0.75 mL of three different concentrations (15-45 \u0026micro;g/mL) of of \u003cem\u003eS. adiyamanensis\u003c/em\u003e samples in distilled water were mixed with 1.25 mL of 0.20 M, PBS pH 6.6 and 1 % (w/w) potassium ferrocyanide. Then, the samples were protonated by 1. 25 mL of 10 % trichloroacetic acid (w/w) and were incubated at 50\u003csup\u003eo\u003c/sup\u003eC for 30 min. Formed Perl\u0026rsquo;s Prussian blue complex, which gives absorption maxima at 700 nm, was measured after the addition of 0.25 mL of 0.1 % FeCl\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e65\u003c/sup\u003e. Spectral color changes of yellow solution into green or blue color, depending upon reducing the capacity of the samples, were observed, and reaction mixtures were analyzed against blank sample that contained distilled water instead of extract solution via Shimadzu UV-1800 UV Spectrophotometer\u003csup\u003e59\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCUPRAC assay:\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e0.5 mL of 10 mM of CuCl\u003csub\u003e2\u003c/sub\u003e, 0.5 mL of 7.5 mM neocuproine, and 0.5 mL of 1.0 M and pH 6.5 NH\u003csub\u003e4\u003c/sub\u003eCH\u003csub\u003e3\u003c/sub\u003eCO\u003csub\u003e2\u003c/sub\u003e buffer were mixed with the plant sample concentration between 15-45 \u0026micro;g/mL in ethanol. the total reaction volume was adjusted to 2 mL with distilled water. Yielded Cu\u003csup\u003e2+\u003c/sup\u003e from Cu\u003csup\u003e+\u003c/sup\u003e-neocuproine complex by electron donor after 30 min incubation a 25\u003csup\u003eo\u003c/sup\u003eC was measured spectrophotometrically using the blue-colored final reaction mixture at 450 nm\u003csup\u003e57,59\u003c/sup\u003e. The blank sample was prepared same solution except ethanol instead of extract solution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFe\u003csup\u003e3+\u003c/sup\u003e- TPTZ Reducing Assay\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e In acidic environments, Fe\u003csup\u003e3+\u003c/sup\u003e-(TPTZ)\u003csub\u003e2\u003c/sub\u003e complexes take one electron from a reducing agent, an antioxidant, and transform into Fe\u003csup\u003e2+\u003c/sup\u003e-(TPTZ)\u003csub\u003e2\u003c/sub\u003e complex, thereby, intensive blue color forms in the reaction mixture\u003csup\u003e65\u003c/sup\u003e. FRAP reagent was prepared by mixing 10 mM TPTZ (in 0.4 mM HCl): 20 mM FeCl\u003csub\u003e3\u003c/sub\u003e: 0.3 M pH 3.6 sodium acetate buffer in a ratio 1:1:10. Reaction components were 0.5 mL of the ethanolic samples (15-45 \u0026micro;g/mL in acetate buffer), 2.25 mL of 20 mM FeCl\u003csub\u003e3\u0026nbsp;\u003c/sub\u003eand 2.25 mL FRAP reagent, resulting in a 5 mL final reaction volume\u003csup\u003e57,59,65\u003c/sup\u003e. The blank sample was prepared with an acetate buffer without the samples. Each reaction\u0026apos;s absorbance was measured at 593 nm at the end of 30 min incubation at 37 \u003csup\u003eo\u003c/sup\u003eC.\u003c/p\u003e\n\u003ch2\u003e2.5. Enzyme Inhibition Profiles of Ethanolic \u003cem\u003eS. adiyamanensis\u003c/em\u003e Extracts\u003c/h2\u003e\n\u003cp\u003eEach inhibition study started with lower concentrations of the extract samples and subsequently increased until more of the enzyme activity was inhibited by the sample addition. The samples\u0026apos; IC\u003csub\u003e50\u003c/sub\u003e values (the concentration of compound where percent inhibition is equal to 50) were calculated using the GraphPad Prism 8.4.0 non-linear regression-[inhibitor]-normalized response (y values 100 down to 0) model.\u003c/p\u003e\n\u003ch3\u003e2.5.1. Determination of \u0026alpha;-Glycosidase Inhibition (AGI)\u003c/h3\u003e\n\u003cp\u003eThe inhibition effect of the plant extracts over \u0026alpha;-glycosidase was investigated by simply incorporating certain concentrations of extracts into the enzyme activity assay. \u0026alpha;-Glycosidase enzyme activity assay principle relies on the enzymatic conversion substrate 4-nitrophenyl-\u0026alpha;-D-glucopyranoside to \u0026alpha;-D-glucopyranoside and p-nitrophenol, resulting yellow-colored product is measured spectrophotometrically at 405 nm\u003csup\u003e66,67\u003c/sup\u003e. The assay reaction consisted of 50 \u0026mu;L of 5 mM p-NPG, 100 \u0026mu;L of 0.1 M of pH 6.9 PBS, and 10 \u0026mu;L of enzyme solution\u003csup\u003e\u003cspan lang=\"TR\"\u003e39,68\u003c/span\u003e\u003c/sup\u003e. Acarbose was used as a positive control for AGI.\u003c/p\u003e\n\u003ch3\u003e2.5.2. Determination of AChE and BChE Inhibition\u003c/h3\u003e\n\u003cp\u003eEthanolic \u003cem\u003eS. adiyamanensis\u003c/em\u003e solutions at varying concentrations for complete inhibition were added to the reaction mixture containing 50 \u0026mu;L of 10 mM DTNB, 50 \u0026mu;L of 10 mM substrate, and 10 \u0026mu;L of enzyme solution in 1 mL of the reaction solution\u003csup\u003e57\u003c/sup\u003e. The substrate was AT for AChE and BT for BChE. Right after enzyme addition, the absorbance at 412 nm was measured for five minutes at minute intervals\u003csup\u003e\u003cspan lang=\"TR\"\u003e57,69\u0026ndash;71\u003c/span\u003e\u003c/sup\u003e. Control reactions and blank reactions were set up without inhibitors and enzymes, respectively. Positive control for AChE and BChE inhibition test was donepezil.\u003c/p\u003e\n\u003ch3\u003e2.5.3. Determination of hCA I and II Inhibition\u003c/h3\u003e\n\u003cp\u003eThe resulting compound after the esterase activity of the carbonic anhydrase (CA) enzyme, a yellow-colored aromatic p-nitrophenolate, gives absorption maxima at 348 nm\u003csup\u003e59,72\u0026ndash;74\u003c/sup\u003e. Various concentrations of the samples in 400 \u0026mu;L of 0.05 M pH=7.4 Tris-SO\u003csub\u003e4\u003c/sub\u003e, 360 \u0026mu;L of 0.07 mM of p-NFA (in 1:25 acetone: water), and 10 \u0026micro;L of the enzyme were mixed and as soon as the addition of the enzyme, the absorbance was monitored by measuring minute intervals for three minutes at 348 nm. Control reactions and blank reactions were set up without inhibitors and enzymes, respectively. These steps were repeated until more than half of enzyme activity was inhibited. The positive control for hCA I and hCA II inhibitors was acetazolamide.\u003c/p\u003e\n\u003ch2\u003e2.6. Statistical Analysis\u003c/h2\u003e\n\u003cp\u003eEach experiment is repeated three times. The results are given as mean \u0026plusmn; SD. In the two-way ANOVA; the mean values of each data set were compared within columns and significant differences were considered to have a value of \u003cem\u003ep\u003c/em\u003e \u0026lt;0.05. All data were processed and graphs were created using GraphPad Prism 8.4.0\u003c/p\u003e"},{"header":" RESULTS \u0026 DISCUSSION","content":"\u003cp\u003eThe antioxidant capacity of the \u003cem\u003eS. adiyamanensis\u003c/em\u003e extracts was investigated through five different colorimetric methods, that rely on two different principles. The first mechanism was the bleaching ability of free radicals, which was determined through DPPH and ABTS radical scavenging assays. According to the DPPH radical scavenging assay result, ethanolic S. adiyamanensis extract was inhibited the 68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03 of % total DPPH radical when 45 \u0026micro;g/mL of the sample applied and the IC\u003csub\u003e50\u003c/sub\u003e value of the extract was calculated as 29.50\u0026thinsp;\u0026plusmn;\u0026thinsp;5.12, while this value was 21.52\u0026thinsp;\u0026plusmn;\u0026thinsp;8.22 for ascorbic acid, 30.65\u0026thinsp;\u0026plusmn;\u0026thinsp;4.89 for BHA, 26.99\u0026thinsp;\u0026plusmn;\u0026thinsp;4.18 for BHT, and 43.26\u0026thinsp;\u0026plusmn;\u0026thinsp;2.26 for trolox (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). P value was determined as \u0026lt;\u0026thinsp;0.05, concluding that no significant difference between the samples was determined. As it can be concluded from these values, \u003cem\u003eS. adiyamanensis\u003c/em\u003e extracts have remarkably slightly lower but notable DPPH radical scavenging capacity. Similarly, the ABTS radical scavenging assay yielded 74.92\u0026thinsp;\u0026plusmn;\u0026thinsp;2.37% of scavenging of total ABTS radical by 45 \u0026micro;g/mL of the \u003cem\u003eS. adiyamanensis\u003c/em\u003e extracts. IC\u003csub\u003e50\u003c/sub\u003e value was calculated as 35.40\u0026thinsp;\u0026plusmn;\u0026thinsp;8.35, while this value was 10.44\u0026thinsp;\u0026plusmn;\u0026thinsp;5.44 for ascorbic acid, 12.78\u0026thinsp;\u0026plusmn;\u0026thinsp;5.43 for BHA, 17.81\u0026thinsp;\u0026plusmn;\u0026thinsp;5.43 for BHT, and 8.59\u0026thinsp;\u0026plusmn;\u0026thinsp;1.25 for trolox (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). As it can be concluded from these values, \u003cem\u003eS. adiyamanensis\u003c/em\u003e extracts have remarkable ABTS radical scavenging properties as both natural and synthetic antioxidants. Results obtained from ABTS were relatively lower, this could be the consequence of the capacity of the methods. Hence, the ABTS method can measure both hydrophilic and lipophilic compounds \u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAmong the Salvia species; DPPH radical scavenging IC\u003csub\u003e50\u003c/sub\u003e values were calculated as 9.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 for methanolic extracts of \u003cem\u003eS. eriophora\u003c/em\u003e, 38.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03 for root, and 93.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 of leaves for the methanolic extract of \u003cem\u003eS. hispanica\u003c/em\u003e, 86.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.010 for ethanolic extract of \u003cem\u003eS. macrochlamys\u003c/em\u003e, 7.05 \u0026micro;g/mL for methanolic \u003cem\u003eS. pilifera\u003c/em\u003e, and 50.22\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03% of DPPH inhibition was obtained when 50 \u0026micro;g/mL of an ethanolic sample of \u003cem\u003eS. cassia\u003c/em\u003e was tested\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan additionalcitationids=\"CR76\" citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e\u003c/sup\u003e. Also, a study conducted by Nasirkandi et al. (2023) revealed that the IC\u003csub\u003e50\u003c/sub\u003e value for DPPH radical scavenging was calculated as 58.05\u0026thinsp;\u0026plusmn;\u0026thinsp;3.31 for \u003cem\u003eS. verticillata\u003c/em\u003e, 56.30\u0026thinsp;\u0026plusmn;\u0026thinsp;3.31 for \u003cem\u003eS. officinalis\u003c/em\u003e, 56.85\u0026thinsp;\u0026plusmn;\u0026thinsp;3.91 for \u003cem\u003eS. multicaulis, 58.78\u0026thinsp;\u0026plusmn;\u0026thinsp;2.69 for S. macrochlamys\u003c/em\u003e, 54.62\u0026thinsp;\u0026plusmn;\u0026thinsp;3.46 for \u003cem\u003eS. candidissima\u003c/em\u003e, and 58.86\u0026thinsp;\u0026plusmn;\u0026thinsp;3.91 for \u003cem\u003eS. nemorosa\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e\u003c/sup\u003e. Similarly, the ABTS radical scavenging IC\u003csub\u003e50\u003c/sub\u003e values were calculated as 6.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.008 for \u003cem\u003eS. eriophora\u003c/em\u003e, 37.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03 for root, and 79.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04 for leaves of \u003cem\u003eS. hispanica\u003c/em\u003e, 15.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 for ethanolic extract of \u003cem\u003eS. macrochlamys\u003c/em\u003e, and 3.52 for methanolic \u003cem\u003eS. pilifera\u003c/em\u003e\u003csup\u003e\u003cem\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e,\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e\u003c/em\u003e\u003c/sup\u003e. These results were evaluated as \u003cem\u003eS. adiyamanensis\u003c/em\u003e has characteristic radical scavenging properties of the genus Salvia, in terms of DPPH and ABTS, as being closer to \u003cem\u003eS. eriophora\u003c/em\u003e and \u003cem\u003eS. hispanica\u003c/em\u003e and ranking in higher levels of the radical scavenging list.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe metal-reducing capacity of the extract was determined through three methods including CUPRAC, FRAP, and Fe\u003csup\u003e3+\u003c/sup\u003e-reducing assays. Both in CUPRAC and Fe\u003csup\u003e3+\u003c/sup\u003e-reducing assay, \u003cem\u003eS. adiyamanensis\u003c/em\u003e yielded greater reducing capacity than synthetic Trolox. The capacity order in the assay in descending order in CUPRAC was BHA\u0026thinsp;\u0026gt;\u0026thinsp;\u003cem\u003eS. Adiyamanensis\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;BHT\u0026thinsp;\u0026gt;\u0026thinsp;Trolox and in Fe\u003csup\u003e3+\u003c/sup\u003e-reducing assay BHA\u0026thinsp;\u0026gt;\u0026thinsp;BHT\u0026thinsp;\u0026gt;\u0026thinsp;S. Adiyamanensis\u0026thinsp;\u0026gt;\u0026thinsp;Trolox as being almost parallel to each other (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). On the other hand, the order in FRAP in descending order was BHT\u0026thinsp;\u0026gt;\u0026thinsp;Trolox\u0026thinsp;\u0026gt;\u0026thinsp;BHA\u0026thinsp;\u0026gt;\u0026thinsp;\u003cem\u003eS. adiyamanensis\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). This difference in the FRAP assay was concluded as the consequence of some drawbacks of the FRAP method, in which the assay cannot measure the antioxidant capacity of certain antioxidants accurately, which can react with ferrous ion (Fe\u003csup\u003e2+)\u003c/sup\u003e and SH group-containing antioxidants. Besides, some polyphenols react more slowly and require longer reaction times for detection\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e. Detailed results of the antioxidant capacity test can be found in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Higher values in Fe\u003csup\u003e3+\u003c/sup\u003e-metal-based methods than in Cu\u003csup\u003e2+\u003c/sup\u003e metal-based methods were evaluated as the result of the CUPRAC reagent being selective because it has a lower redox potential than those of Folin or ferric ion-based oxidative reagents\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e. The optimum pH for the CUPRAC assay is 7.0 close to physiological pH, simulating antioxidant action under real conditions. This method is capable of measuring both hydrophilic and lipophilic antioxidants\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAmong the Salvia species, in CUPRAC method is almost applied the same as in this study, reducing capacity in absorbance unit was determined as 1.606\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006 for 50 \u0026micro;g/mL methanolic extracts of \u003cem\u003eS. eriophora\u003c/em\u003e, 1.056\u0026thinsp;\u0026plusmn;\u0026thinsp;0.019 for root, and 0.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.008 of leaves for the methanolic extract of 60 \u0026micro;g/mL \u003cem\u003eS. hispanica, 0.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/em\u003e for 30 \u0026micro;g/mL ethanolic extract of \u003cem\u003eS. macrochlamys\u003c/em\u003e, and 1.211\u0026thinsp;\u0026plusmn;\u0026thinsp;0.013 for 30 \u0026micro;g/mL methanolic \u003cem\u003eS. pilifera in\u003c/em\u003e previous studies\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e,\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e\u003c/sup\u003e. In FRAP, \u003cem\u003e1.944\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/em\u003e for 50 \u0026micro;g/mL methanolic extracts of \u003cem\u003eS. eriophora\u003c/em\u003e, 0.847\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003 for root, and 0.587\u0026thinsp;\u0026plusmn;\u0026thinsp;0.008 for leaves of 60 \u0026micro;g/mL methanolic extract of \u003cem\u003eS. hispanica\u003c/em\u003e, 0.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 for 30 \u0026micro;g/mL ethanolic extract of \u003cem\u003eS. macrochlamys\u003c/em\u003e and 1.722\u0026thinsp;\u0026plusmn;\u0026thinsp;0.008 for 30 \u0026micro;g/mL methanolic \u003cem\u003eS. pilifera in\u003c/em\u003e previous studies\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e,\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e\u003c/sup\u003e. In the Fe\u003csup\u003e3+\u003c/sup\u003e-reducing assay, 1.662\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002 for 50 \u0026micro;g/mL methanolic extracts of \u003cem\u003eS. eriophora\u003c/em\u003e, 0.490\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003 for root, and 0.253\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004 for leaves of 60 \u0026micro;g/mL methanolic extract of \u003cem\u003eS. hispanica\u003c/em\u003e, 0.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02 01 for 30 \u0026micro;g/mL ethanolic extract of \u003cem\u003eS. macrochlamys\u003c/em\u003e and 1.762\u0026thinsp;\u0026plusmn;\u0026thinsp;0.008 008 for 30 \u0026micro;g/mL methanolic \u003cem\u003eS. pilifera in\u003c/em\u003e previous studies\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e,\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e\u003c/sup\u003e. These results were evaluated as \u003cem\u003eS. adiyamanensis\u003c/em\u003e has characteristic metal-reducing properties of the genus Salvia, in terms of DPPH and ABTS, as being closer to \u003cem\u003eS. eriophora\u003c/em\u003e and \u003cem\u003eS. hispanica\u003c/em\u003e\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e,\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e\u003c/sup\u003e. Besides, antioxidant capacity relatedness with \u003cem\u003eS. pilifera\u003c/em\u003e was also noticed\u003csup\u003e\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAntioxidant results of 45ug/mL of the ethanolic \u003cem\u003eS. adiyamanensis\u003c/em\u003e extracts\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAntioxidants\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eABTS\u003csup\u003e\u0026middot;+\u003c/sup\u003e scavenging\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eDPPH∙ scavenging\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eFRAP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eCUPRAC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003eFe\u003csup\u003e3+\u003c/sup\u003e-reducing\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e(IC\u003c/b\u003e\u003csub\u003e\u003cb\u003e50)\u003c/b\u003e\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003er\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(IC\u003c/b\u003e\u003csub\u003e\u003cb\u003e50)\u003c/b\u003e\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003er\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eλ (\u003c/b\u003e593nm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003er\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eλ (\u003c/b\u003e450 nm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003er\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003eλ (\u003c/b\u003e700 nm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003er\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAscorbic acid\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e21.52\u0026thinsp;\u0026plusmn;\u0026thinsp;8.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9387\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e10.44\u0026thinsp;\u0026plusmn;\u0026thinsp;5.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.9756\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBHA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e30.65\u0026thinsp;\u0026plusmn;\u0026thinsp;4.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9742\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e12.78\u0026thinsp;\u0026plusmn;\u0026thinsp;5.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.9744\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.9986\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.9948\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.9983\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBHT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e26.99\u0026thinsp;\u0026plusmn;\u0026thinsp;4.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9809\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e17.81\u0026thinsp;\u0026plusmn;\u0026thinsp;5.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.9689\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.9938\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.9989\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.9972\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTrolox\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e43.26\u0026thinsp;\u0026plusmn;\u0026thinsp;2.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9888\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e8.59\u0026thinsp;\u0026plusmn;\u0026thinsp;1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.9338\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.9558\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.9988\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.9990\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eS. adiyamanensis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e29.50\u0026thinsp;\u0026plusmn;\u0026thinsp;5.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9714\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e35.40\u0026thinsp;\u0026plusmn;\u0026thinsp;8.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.9005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.9844\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.9916\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.9921\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\u003cdiv id=\"Sec17\"\u003e\n \u003ch2\u003e4.2 Estimation of Enzyme Inhibition Property of Ethanolic \u003cem\u003eS. adiyamanensis\u003c/em\u003e extract\u003c/h2\u003e\n \u003cp\u003eThe enzyme inhibition profile of \u003cem\u003eS. adiyamanensis\u003c/em\u003e extracts was investigated against therapeutic targets of metabolic diseases in mild to moderate stages. These enzymes were AChE, BChE, α-glycosidase, hCA I, and hCA II. Certain concentrations of the extracts were added in concentration concentration-dependent manner, IC\u003csub\u003e50\u003c/sub\u003e values were calculated after more than half of enzyme activity was inhibited, and the results were compared with the standard drugs that were commercially available and used in the treatment of the diseases.\u003c/p\u003e\n \u003cp\u003eThe data obtained from previous studies describing the role of AChE and BChE explains that the decrease in the activity of these enzymes in the central nervous system increases the concentration of acetylcholine (ACh). This improves cognitive functions and delays neurodegenerative lesions including amyloid-β (Aβ) plaques in Alzheimer's disease (AD)\u003csup\u003e79,80\u003c/sup\u003e. Due to unfavorable pharmacokinetic parameters of registered compounds up to now, researchers worldwide search for new AChE and BChE inhibitors for mild to moderate treatment. New compounds might be found in plants containing the following groups of compounds: alkaloids (indoles, steroids, and piperidines), phenylpropanoids (furanocoumarins, xanthones, and flavonoids), and terpenoids (diterpenes) have been reported so far with their effectiveness on the activity of AChE\u003csup\u003e81–86\u003c/sup\u003e. According to the result obtained from this study, \u003cem\u003eS. adiyamanensis\u003c/em\u003e ethanolic extract inhibited the activity of AChE and BChE with 191.3 µg/mL and 8.02 µg/mL IC\u003csub\u003e50\u003c/sub\u003e values. While these values were 12.22 µg/mL and 8.82 µg/mL for donepezil. According to the studies reported IC\u003csub\u003e50\u003c/sub\u003e values for AChE and BChE were calculated as 9.91 ± 0.058 µg/mL and 5.17 ± 0.043 µg/mL for \u003cem\u003eS. eriophora\u003c/em\u003e, 19.1 µg/mL and 13.1 µg/mL for \u003cem\u003eS. hispanica\u003c/em\u003e, 1.622 µg/mL (AChE) for \u003cem\u003eS. macrochlamys\u003c/em\u003e, 94.93 µg/mL and 69.05 µg/mL for \u003cem\u003eS. pilifera\u003c/em\u003e, respectively and no cholinergic activity was determined by \u003cem\u003eS. cassia\u003c/em\u003e\u003csup\u003e8,48,75–77\u003c/sup\u003e. IC\u003csub\u003e50\u003c/sub\u003e value difference was interpreted as activity measurement method variability as well as the solvent of extraction and species. Together with this, it can be concluded that \u003cem\u003eS. adiyamanensis\u003c/em\u003e extracts had remarkable cholinergic activity when the results were compared with both the standard drug donepezil and previous findings reported in research with other Salvia species.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eEnzyme inhibition results of \u003cem\u003eS. adiyamanensis\u003c/em\u003e ethanolic extracts\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"11\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSamples\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAG\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAChE\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eBChE\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003ehCA I\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003ehCA II\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIC\u003csub\u003e50\u003c/sub\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003er\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIC\u003csub\u003e50\u003c/sub\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003er\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIC\u003csub\u003e50\u003c/sub\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003er\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIC\u003csub\u003e50\u003c/sub\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003er\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIC\u003csub\u003e50\u003c/sub\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003er\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eS. adiyamanensis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9112\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e191.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9732\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9963\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e32.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9819\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9519\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStandards*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9656\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9996\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9836\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e55.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9963\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e49.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9957\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e*Standards in the table refer to acarbose for AG, donepezil for AChE and BChE, and Acetazolamide for hCA I and hCA II.\u003c/p\u003e\n \u003cp\u003eα-Glycosidase is a crucial enzyme that catalyzes polysaccharides into monosaccharides in carbohydrate digestion\u003csup\u003e87\u003c/sup\u003e. Therefore, AGIs can decrease the D-glucose transition from intestine by the delay of complex carbohydrate breakdown, resulting in lower postprandial plasma glucose levels and control of postprandial plasma hyperglycemia. Many attempts have been made in recent years to uncover efficient AGIs from natural sources to build a physiologic functional diet or lead compound for diabetes treatment due to rich constituents including flavonoids, terpenoids, phenolics and derivatives, and tannins being biologically active\u003csup\u003e39,42,57,67,83,88–91\u003c/sup\u003e. Here, ethanolic \u003cem\u003eS. adiyamanensis\u003c/em\u003e extract was subjected to α-glycosidase inhibition analysis and according to the results, the extract inhibited the α-glycosidase activity with a 30.78 µg/mL IC\u003csub\u003e50\u003c/sub\u003e value. In contrast, this value was 25.43 µg/mL for the standard diabetes drug, acarbose. According to the previous studies, α-glycosidase was inhibited with IC\u003csub\u003e50\u003c/sub\u003e values 5.54 ± 0.050 µg/mL \u003cem\u003eS. eriophora\u003c/em\u003e, 0.530 µg/mL for \u003cem\u003eS. macrochlamys\u003c/em\u003e, and 23.28 µg/mL for \u003cem\u003eS. pilifera\u003c/em\u003e\u003csup\u003e48,75,77\u003c/sup\u003e. Shojaeifard et. al (2023), have been tested fifty different types of Salvia species against α-glycosidase enzymes, and they concluded \u003cem\u003ethat S. multicaulis, S. santolinifolia, S. dracocephaloides\u003c/em\u003e, and \u003cem\u003eS. eremophila\u003c/em\u003e were stronger inhibitors than acarbose with IC\u003csub\u003e50\u003c/sub\u003e values in the range of 26.23–92.35 µg/mL\u003csup\u003e87\u003c/sup\u003e. Based on these findings, \u003cem\u003eS. adiyamenensis\u003c/em\u003e was concluded as \u003cem\u003eS. adiyamanensis\u003c/em\u003e has powerful potential to be a natural α-glycosidase inhibitor. According to the study conducted in 2025, \u003cem\u003eS. aucheri, S. candidissima, S. divaricata, S. virgata, S. multicaulis, S. palestine, S. trichoclada, and S. cerino-pruinosa\u003c/em\u003e have been tested against various metabolic enzymes including α-glycosidase and they have determined that alcoholic extracts of all species have been yielded remarkable AG inhibition property which can be accepted as better than that acarbose \u003csup\u003e92\u003c/sup\u003e.\u003c/p\u003e\n \u003cp\u003eCAs have a regulatory role in many physiological processes such as gluconeogenesis, ureagenesis, fluid secretion, acid/base balance, gastric acid production, and transport of CO\u003csub\u003e2\u003c/sub\u003e from tissues to the lungs (in the form of bicarbonate) through the blood\u003csup\u003e70,73,93\u003c/sup\u003e. The critical importance of CAs in the regulation of these processes, they play a major role in the pathophysiology of various diseases like hemolytic anemia, glaucoma, renal tubular acidosis, osteoporosis, neuropathic pain, colorectal cancer, etc. As a result, carbonic anhydrase inhibitors (CAIs) find therapeutic applications for the treatment of various clinical disorders\u003csup\u003e39,55,72–74,82,83,85,94\u003c/sup\u003e. There sixteen isoforms of CAs have been identified and each of them has a different role in the treatment of various diseases\u003csup\u003e39,55,73\u003c/sup\u003e. For instance, while CA I and CA II are linked to hemolytic anemia, CA II is also associated with glaucoma, epilepsy, edema, and altitude sickness \u003csup\u003e94–96\u003c/sup\u003e. A wide range of diseases from cancer to diabetes, have been linked to different CA isoforms\u003csup\u003e94\u003c/sup\u003e. Therefore, it is important to identify and determine novel CAIs. Here, ethanolic \u003cem\u003eS. adiyamanensis\u003c/em\u003e extracts were tested against hCA I and hCA II enzymes to evaluate its potential as a novel CAI. According to the results, \u003cem\u003eS. adiyamanensis\u003c/em\u003e extract inhibited the activity of hCA I and hCA II enzymes with 32.68 µg/mL and 54.82 µg/mL IC\u003csub\u003e50\u003c/sub\u003e values, while these values were 55.10 µg/mL and 49.80 µg/mL for standard drug, acetazolamide. Based on the literature findings, hCA I and hCA II enzymes were inhibited with 39.2 µg/mL and 38.5 µg/mL IC\u003csub\u003e50\u003c/sub\u003e values by \u003cem\u003eS. hispanica\u003c/em\u003e, 3097.0 ± 300.6 µg/mL for \u003cem\u003eS. miltiorrhiza\u003c/em\u003e\u003csup\u003e97\u003c/sup\u003e. Results from \u003cem\u003eS. hispanica\u003c/em\u003e hCA inhibition test results from the literature were quite similar to those obtained in this study \u003csup\u003e8\u003c/sup\u003e. Details of enzyme inhibition study can be found in Table 2.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\"\u003e\n \u003ch2\u003e4.3. Phytochemical Analysis of Ethanolic \u003cem\u003eS. adiyamanensis\u003c/em\u003e Extract\u003c/h2\u003e\n \u003cp\u003ePhytochemical analysis of the ethanolic \u003cem\u003eS. adiyamanensis\u003c/em\u003e extract was performed through spectrophotometric TFC/TPC and chromatographic LC-MS/MS methods. The TPC of the extract was 543 mg GAE /g of extract and the TFC of the extract was 122.17 ± 0.12 mg QE/g of the extract have been determined. In addition, the extraction yield was calculated as 28% with methanol extraction. The TPC and the TFC values were calculated as 36.35 mg GAE per gram extract and 68.70 QE/g extracts for \u003cem\u003eS. pilifera\u003c/em\u003e, 39.87 ± 1.12 QE/g extracts, and 27.95 ± 0.36 QE/g extracts for \u003cem\u003eS. cassia\u003c/em\u003e, 150.1 ± 1.1 mg GAE/g and 38.9 ± 3.1 mg QE/g for \u003cem\u003eS. macrochlamys\u003c/em\u003e, 62.35 ± 0.09 mg GAE/g and 46.93 ± 0.05 mg QE/g for \u003cem\u003eS. hispanica\u003c/em\u003e, 102.00 mg GAE/g and 22.44 ± 0.49 mg QE/g for \u003cem\u003eS. aucheri, 66.51 ± 1.69\u003c/em\u003e mg GAE/g and 23.23 ± 0.37 mg QE/g \u003cem\u003eS. candidissima\u003c/em\u003e, 54.83 ± 1.29 mg GAE/g and 35.97 ± 0.39 mg QE/g for \u003cem\u003eS. divaricate, 96.93 ± 3.06\u003c/em\u003e mg GAE/g and 25.72 ± 0.07 mg QE/g for \u003cem\u003eS. virgata\u003c/em\u003e, 92.16 ± 4.19 mg GAE/g and 34.89 ± 0.28 mg QE/g \u003cem\u003eS. multicaulis\u003c/em\u003e, 50.13 ± 0.57 GAE/g and 37.00 ± 0.08 mg QE/g for \u003cem\u003eS. palestina\u003c/em\u003e, 105.13 ± 12.10 mg GAE/g and 32.24 ± 0.51 mg QE/g for \u003cem\u003eS. trichoclada\u003c/em\u003e, 124.15 ± 0.17 GAE/g and 35.93 ± 0.57 mg QE/g for \u003cem\u003eS. cerinopruinosa\u003c/em\u003e, respectively\u003csup\u003e8,92\u003c/sup\u003e. These results concluded that Salvia phenolic and flavonoid content signs were detected in the novel Turkish Sage content.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTablo 3.\u003c/strong\u003e Quantitative LC-MS/MS Results of ethanolic \u003cem\u003eS. adiyamanensis\u003c/em\u003e extract: LOD; Limit of Detection\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Taba\" border=\"1\"\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCompound\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAcquisition Time\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eResponse\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eConcentration (ng/mL)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuinic Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.359\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e959\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e335.7590\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFumaric Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGallic Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.606\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePyrogallol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.696\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCyanidin-3-o-glucoside\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.597\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.0745\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChlorogenic Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.599\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e89534\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3366.8520\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKeracyanin Chloride\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.654\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.6532\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeonidin-3-o-glucoside\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.959\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCatechin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.978\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4-OH-Benzoic Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6265\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e345.2810\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCaffeic Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.375\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64687\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1087.8426\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEpicatechin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.413\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEpigallocatechin Gallate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.510\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVanillic Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.579\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVitexin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.598\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4049\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.4587\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNaringin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.871\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e793\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.6222\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSyringic Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.895\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHesperidin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.929\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e238.0012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEllagic Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.992\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep-Coumaric Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.246\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3910\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40,1215\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTaxifolin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.267\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4328\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSinapic Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.388\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRosmarinic Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.468\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1226526\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e301734.0851\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFerulic Acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.548\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVanillin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.623\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMyricetin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.889\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eResveratrol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.185\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLuteolin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.327\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e295703\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2465.8651\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuercetin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.427\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e72880\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1703.5567\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eApigenin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.879\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e126078\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1412.7408\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNaringenin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.907\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6929\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.4182\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIsorhamnetin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.0130\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGalangin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15.183\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCurcumin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15.454\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChrysin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15.489\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;LOD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eLC-MS/MS analysis for ethanolic extract of \u003cem\u003eS. adiyamanensis\u003c/em\u003e was performed against a total of thirty-five compounds including organic acid, phenolics, and flavonoids\u003csup\u003e62\u003c/sup\u003e. According to the results, sixteen different compounds were identified and six of them were determined in ppm level including in descending order as rosmarinic acid, chlorogenic acid, luteolin, quercetin, apigenin, and caffeic acid. Relatively lower amounts of other phenolics and organic acids such as quinic acid, cyanidin-3-o-glucoside, keracyanin chloride, 4-OH-benzoic acid, vitexin, naringin, hesperidin, p-coumaric acid, naringenin, and isorhamnetin. Although the taxifolin response has been determined, the metabolite could not be determined due to its amount being under the limit of detection. The chromatogram and the quantitative results of LC-MS/MS analysis can be found in Fig. 3. and Table 3, respectively. In a study conducted to analyze phenolics in eight different types of Salvia species against quite a wide range of standard phenolics; Malic acid, isocitric acid, citric acid rosmarinic acid, Danshensu, caffeic acid, sagerinic acid isomer, oxo-dihydroxy‐octadecenoic acid, and trihydroxy‐octadecenoic acid were detected in all Salvia species including \u003cem\u003eS. aucheri, S. candidissima, S. divaricate, S. virgata, S. multicaulis, S. palestina, S. trichoclada\u003c/em\u003e and \u003cem\u003eS. cerinopruinosa\u003c/em\u003e \u003csup\u003e26\u003c/sup\u003e. Fumaric acid, quercetagetin-3,6-dimethyl ether, and salvigenin have been majorly detected in \u003cem\u003eS. pilifera\u003c/em\u003e methanolic extract; rosmarinic acid, syringic acid, luteolin, apigenin, nepedin, hispidulin, penduletin, acacetin, and hederagenin in ethanolic \u003cem\u003eS. macrochlamys\u003c/em\u003e extract; salvigenin and fumaric acid in methanoli\u003cem\u003ec S. eriophora;\u003c/em\u003e rosmarinic acid, quinic acid, and caffeic acid in \u003cem\u003eS. hispanica\u003c/em\u003e extracts; luteolin and rutin in \u003cem\u003eS. fruticosa\u003c/em\u003e, rosmarinic acid \u003cem\u003ein S. officinalis\u003c/em\u003e\u003csup\u003e8,14,48,75,77,98\u003c/sup\u003e. Quercetin is a well-known flavonoid with a wide range of biological activity, however, in recent years, its effects on the digestion of lipids and carbohydrates have been extremely popular to be a potential natural candidate as an antidiabetic agent\u003csup\u003e99–101\u003c/sup\u003e.\u003c/p\u003e\n \u003cp\u003eAs previously reported, the antioxidant capacity of the Salvia extracts is mostly related to its rosmarinic acid content, an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid, and is a natural polyphenol carboxylic acid, an ester of caffeic and 3,4-dihydroxyphenyllactic acids, a good potential source of antioxidants for food protection and pharmaceutical applications\u003csup\u003e67\u003c/sup\u003e. In a study investigating, the effect of rosmarinic acid against CA IX and XII isoenzymes, AChE, BChE, lactoperoxidase (LPO), and glutathione S-transferase (GST) were evaluated and it has been reported that rosmarinic acid showed low micromolar inhibition against both CA isoenzymes (CA IX and XII) and LPO, nanomolar inhibition against GST and picomolar inhibition against ACE and BChE. The results showed that rosmarinic acid moderately inhibited both CA isoenzymes, but effectively inhibited GST, ACE, and BChE\u003csup\u003e102\u003c/sup\u003e. The second abundant metabolite was chlorogenic acid, which is a member of the chlorogenic acid family (CGA) abundant in dietary phenolic acid compounds in plants, conjugating the hydroxy group of quinic acid and the carboxyl group of caffeic acid as the parent structure. The CGA family has shown multiple protective effects on mitigating many chronic inflammatory and age-related disorders through exerting the central actions of anti-inflammation, antioxidation, and metabolic homeostasis modulation\u003csup\u003e103,104\u003c/sup\u003e. In a study that was conducted to investigate enzyme inhibition properties of chlorogenic acid, IC\u003csub\u003e50\u003c/sub\u003e values over α-amylase and α-glucosidase were determined as 9.10 µg/mL and 9.24 µg/mL as being remarkably significant\u003csup\u003e105\u003c/sup\u003e.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe ethanolic extract of \u003cem\u003eS. adiyamanensis\u003c/em\u003e exhibited significant antioxidant and enzyme inhibitory properties, positioning it as a promising natural source for therapeutic applications. The extract demonstrated strong DPPH and ABTS radical scavenging capacities, comparable to well-known commercial natural and synthetic antioxidants such as ascorbic acid, BHA, BHT, and Trolox. Additionally, its metal-reducing capacity was notably high, surpassing Trolox in certain assays like CUPRAC and Fe\u003csup\u003e3+\u003c/sup\u003e-reducing assays, further reinforcing its potential as an effective antioxidant.\u003c/p\u003e \u003cp\u003eThe enzyme inhibition profile also highlighted the medicinal value of \u003cem\u003eS. adiyamanensis\u003c/em\u003e, with remarkably high inhibitory effects against key therapeutic targets related to metabolic diseases. Specifically, the extract showed potent inhibition of AChE and BChE, suggesting its potential in managing neurodegenerative conditions like Alzheimer\u0026rsquo;s disease. Furthermore, its α-glucosidase inhibition activity supports its application in managing diabetes, as it demonstrates comparable efficacy to acarbose. The extract\u0026rsquo;s inhibition of hCA I and hCA II enzymes further indicates its relevance in treating conditions like glaucoma and hemolytic anemia\u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e,\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e,\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e,\u003cspan citationid=\"CR96\" class=\"CitationRef\"\u003e96\u003c/span\u003e,\u003cspan citationid=\"CR106\" class=\"CitationRef\"\u003e106\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePhytochemical analysis revealed a rich presence of bioactive compounds, particularly phenolic acids, and flavonoids, including rosmarinic acid, chlorogenic acid, luteolin, quercetin, and caffeic acid, which are likely responsible for the observed biological activities\u003csup\u003e\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e,\u003cspan additionalcitationids=\"CR100 CR101 CR102 CR103\" citationid=\"CR99\" class=\"CitationRef\"\u003e99\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR104\" class=\"CitationRef\"\u003e104\u003c/span\u003e,\u003cspan additionalcitationids=\"CR108 CR109\" citationid=\"CR107\" class=\"CitationRef\"\u003e107\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR110\" class=\"CitationRef\"\u003e110\u003c/span\u003e\u003c/sup\u003e. These findings align \u003cem\u003eS. adiyamanensis\u003c/em\u003e with other Salvia species known for their antioxidant and medicinal properties\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan additionalcitationids=\"CR12 CR13 CR14 CR15 CR16 CR17\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e,\u003cspan additionalcitationids=\"CR112 CR113\" citationid=\"CR111\" class=\"CitationRef\"\u003e111\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR114\" class=\"CitationRef\"\u003e114\u003c/span\u003e\u003c/sup\u003e. Overall, Salvia a\u003cem\u003ediyamanensis\u003c/em\u003e shows substantial potential for further development into a functional natural product for the prevention and management of various diseases, particularly neurodegenerative disorders, diabetes, and conditions involving carbonic anhydrase enzymes. Its diverse pharmacological activities and its phytochemical richness warrant additional research to fully explore its therapeutic potential.\u003c/p\u003e \u003cp\u003eWhile the \u003cem\u003eSalvia\u003c/em\u003e genus is known for its medicinal and therapeutic properties, some species within this genus have been reported to exhibit varying degrees of toxicity, particularly when consumed in large quantities or improperly prepared\u003csup\u003e\u003cspan citationid=\"CR115\" class=\"CitationRef\"\u003e115\u003c/span\u003e,\u003cspan citationid=\"CR116\" class=\"CitationRef\"\u003e116\u003c/span\u003e\u003c/sup\u003e. Certain \u003cem\u003eSalvia\u003c/em\u003e species, such as \u003cem\u003eS. divinorum\u003c/em\u003e, contain psychoactive compounds like salvinorin A, which can induce intense hallucinogenic effects and may pose risks to mental health and well-being when used recreationally\u003csup\u003e\u003cspan citationid=\"CR117\" class=\"CitationRef\"\u003e117\u003c/span\u003e\u003c/sup\u003e. Other species, depending on their chemical composition, may contain compounds that could be toxic to specific organs or systems if ingested inappropriately\u003csup\u003e\u003cspan citationid=\"CR115\" class=\"CitationRef\"\u003e115\u003c/span\u003e,\u003cspan citationid=\"CR116\" class=\"CitationRef\"\u003e116\u003c/span\u003e\u003c/sup\u003e. However, many \u003cem\u003eSalvia\u003c/em\u003e species, have not shown significant toxicity in the doses typically used for medicinal purposes, with studies indicating a relatively safe profile when consumed in moderate amounts or when used topically\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR111\" class=\"CitationRef\"\u003e111\u003c/span\u003e\u003c/sup\u003e. Despite this, further research into the toxicity and safety of various \u003cem\u003eSalvia\u003c/em\u003e species is necessary to better understand their potential risks and to ensure their safe and effective use in traditional and modern therapeutic applications.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the data supporting the findings of this study are available within the paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIlhami Gulcin is a member Turkish Academy of Sciences (T\u0026Uuml;BA). He would liken to extend his sincere appreciation to the T\u0026Uuml;BA for their financial support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA.Z.T. carried out the experiment, methodology, and investigation. K.A. carried out the experiment, methodology, and investigation. İ.G. designed the study, analyzed data, supervised the experiment and prepared the manuscript. All the authors gave their consent for the publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTe author declares no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWu, Y. B. \u003cem\u003eet al.\u003c/em\u003e Constituents from salvia species and their biological activities. \u003cem\u003eChem. Rev. \u003c/em\u003e\u003cstrong\u003e112\u003c/strong\u003e, 5967\u0026ndash;6026 (2012).\u003c/li\u003e\n\u003cli\u003eZhumaliyeva, G. \u003cem\u003eet al.\u003c/em\u003e Natural Compounds of Salvia L. 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Salvia divinorum: Exposures reported to a statewide poison control system over 10 years. \u003cem\u003eJournal of Emergency Medicine\u003c/em\u003e \u003cstrong\u003e40\u003c/strong\u003e, 643\u0026ndash;650 (2011).\u003c/li\u003e\n\u003c/ol\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":"S. adiyamenensis, phytochemical profiling, antioxidant capacity, enzyme inhibition, metabolic disease","lastPublishedDoi":"10.21203/rs.3.rs-6213034/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6213034/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIn this study, the antioxidant effect of ethanolic extracts were prepared from the aerial part of \u003cem\u003eSalvia adiyamanensis\u003c/em\u003e was investigated through five methods, including DPPH\u0026sdot;, ABTS, and Fe\u003csup\u003e3+\u003c/sup\u003e, Cu\u003csup\u003e2+\u003c/sup\u003e, Fe\u003csup\u003e3+\u003c/sup\u003e-TPTZ reducing assays. The IC50 values of extract was determined as 35.40\u0026thinsp;\u0026plusmn;\u0026thinsp;8.35 and 29.50\u0026thinsp;\u0026plusmn;\u0026thinsp;5.12 \u0026micro;g/mL for DPPH and ABTS radicals scavenging assays. The enzyme inhibition property of the extract was investigated against α-glycosidase, acetylcholinesterase, butyrylcholinesterase, human carbonic anhydrase I, and human carbonic anhydrase II, as a result, IC\u003csub\u003e50\u003c/sub\u003e values were determined as 30.78, 191.3, 8.02, 32.68 and 54.82 \u0026micro;g/mL, respectively. LC-MS/MS revealed that \u003cem\u003eS. adiyamanensis\u003c/em\u003e compromised the characteristic phenolics including rosmarinic acid, chlorogenic acid, luteolin, quercetin, apigenin, and caffeic acid of the Salvia genus. These findings strongly suggest that \u003cem\u003eS. adiyamanensis\u003c/em\u003e has the potential to be a natural medicine for the treatment of metabolic diseases such as diabetes, Alzheimer\u0026rsquo;s disease, or glaucoma.\u003c/p\u003e","manuscriptTitle":"Phytochemical Analysis, Antioxidant, Anticholinergic, Antidiabetic, and Antiglaucoma Potentials of Sage (Salvia adiyamanensis)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-10 16:26:08","doi":"10.21203/rs.3.rs-6213034/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":"866d2c57-07c7-4e5f-93b8-ed27171376c1","owner":[],"postedDate":"April 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":46727317,"name":"Biological sciences/Biochemistry"},{"id":46727318,"name":"Biological sciences/Biological techniques"},{"id":46727319,"name":"Physical sciences/Chemistry"}],"tags":[],"updatedAt":"2025-05-12T11:38:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-10 16:26:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6213034","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6213034","identity":"rs-6213034","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}