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Purpose Freshwater fish Pangasius sutchi was used in this study as a vertebrate model. We evaluated the induction of certain antioxidant enzymes in various vital organs. The radioprotective efficacy of Gymnema sylvestre leaves extract (GS) [25 mg/kg Body Weight (B.W)] and its bioactive compound Gymnemagenin (GG) [0.3 mg/kg B.W] was compared with Amifostine (Ami), the only radioprotector clinically approved by the US-FDA [Ami- 83.3 mg/kg B.W] against different doses of gamma radiation - 60Co (Lethal Dose: LD30-9.2 Gy, LD50-10.2 Gy and LD70-11.4 Gy). Materials and methods This study was done via stress marker enzymes, cell cycle analysis (CCA) and DNA damage assay prediction with molecular docking, which are reported here for the first time. The results indicate an elevated LPO level and decreased level of CAT, SOD and GSH due to oxidative stress initiation by 60Co Ionizing Radiation (IR) on 4th day and slightly reduced on 32nd day while the reverse observed when the fishes were pretreated with Ami, GS and GG. Similarly, CCA and dead/live cells counts were conducted with pretreatment of Ami, GS and GG against 60Co IR dose (LD50-10.2 Gy). Results In CCA, G0/G1 phase was observed to be the highest in Ami and lowest in GG, against 60Co IR doses 10.2 Gy which was 51.76 ± 7.55. The dead cells range observed in pretreated group of Ami, GS and GG was lowest in Ami and highest in GG and live cells (highest in Ami and lowest in GG) as compared to 60Co IR group (86.43 ± 3.42 and 8.77 ± 5.95). Thus, antioxidant profile improvement by oxidative stress reduction and gradual progression of different phases of cell cycle except the apoptotic phase along with the live cells counts indicates that the radio-protective efficacy of GS is similar to Ami. Conclusion Predictive assessment was carried out by docking of Ami, various components of GS with p53, NF-κβ cells and Rad51 proteins structures responsible for CCA, apoptosis and repair mechanism. These structural proteins were docked with other structural proteins like USP7, TNF-α and partner and localizer of BRCA2 associated (PALB2/BRCA2) complex which made us perform these systemic efforts to find the functional activity of these known radio-protectants.

The present study aims to evaluate the ameliorative effect of crude and solvent partitioned fractions of Gymnema sylvestre in alloxan-induced hyperglycemic and dyslipidemic rats. The extract and fractions of Gymnema sylvestre were administered to alloxan (120 mg/kg) induced diabetic rats at doses of 100, 300, and 600 mg/kg. Metformin (100 mg/kg) was used as the reference drug. All treatments were administered daily for 14 days through the oral route. Effects of the treatments on blood glucose levels, body weight, and serum lipid profiles were monitored. The results revealed that all the extracts and fractions were able to reduce the blood glucose levels and improved the body weight of diabetic rats, with more pronounced effects at the treatment of 300 mg/kg of crude methanol and ethyl acetate fraction. The blood glucose of diabetic untreated rats continued to increase up to the time of euthanization. There were significant reductions (p

Objectives. The amount of patients with diabetes is increasing, and such patients experience several long-term complications. Therefore, finding a method to treat the disease and its complications is an urgent issue worldwide. In Vietnam, Phyllanthus amarus Schum. & Thonn. (PA) and Gymnema sylvestre R. Br. (GS) are common herbs used in traditional therapy including diabetes treatment. This study aimed to combine PA and GS to extend their bioactivities in antidiabetes, antioxidant, and anti-inflammatory treatments.Methods. Here, PA and GS powders were mixed at different ratios for extraction. Ethanolic extract was used to detect bioactive compounds, bioactivities, and appropriate ratios of the mixtures.Results. The optimal ratio for the PA and GS combination was 2 : 1 (g/g). The ethanolic extraction of the 2 : 1 sample at 50°C over two hours with a solid/liquid ratio of 1 : 10 achieved a high yield of 14.37%. This sample exhibited good α-glucosidase inhibition activity with a half-maximal inhibitory concentration (IC50) of 9.74 µg/mL, antioxidant activity with an IC50 of 29.87 µg/mL, and anti-inflammatory activity with an IC15 of 400 µg/mL.Conclusions. The study confirmed that combining PA and GS can have high α-glucosidase inhibition as well as antioxidant and anti-inflammatory effects.

Background Gymnema sylvestre is a reputable medicinal plant commonly explore for the management of diabetes and other ailments in traditional medicine. In the present study, we investigated the phytochemical compositions and effect of crude extract, hexane, and ethyl-acetate fractions of Gymnema sylvestre on biochemical and hematological parameters of Wistar rats. Methods Albino rats were distributed randomly into a control group and nine treatment groups orally administered crude extract and fractions of Gymnema sylvestre (100, 300, and 600 mg/kg BW) for 21 days. Liver and kidney function indices, as well as hematological parameters, were monitored. Results Our results revealed that the crude methanol extract contains flavonoids (8.56 ± 0.50 mg/g), alkaloids (13.84 ± 0.67 mg/g), total phenol (1.98 ± 0.50 mg/g), saponins (23.85 ± 0.35 mg/g) and tannins (16.00 ± 0.34 mg/g). The crude methanol, ethyl acetate and n-hexane fractions of Gymnema sylvestre had LD50 greater than 5000 mg/kg BW in acute oral toxicity test. The extract and fractions at 300 and 600 mg/kg BW cause loss of body weight of the rats, significantly altered (p p > 0.05) alterations to the levels of biochemical and hematological parameters when compared with the non-treated control. Conclusion Gymnema sylvestre at sub-acute doses of 300 and 600 mg/kg BW could compromise the functional integrity of the rats’ liver and kidney. The study, therefore, suggested the use of Gymnema sylvestre for oral remedy at a dose of 100 mg/kg or below.

We report on activity-guided investigation of the key antisweet principles of Gymnema sylvestre. Orosensory-guided fractionation by means of solid phase extraction, preparative 2D-LC, and semipreparative HPLC followed by accurate MS and 1D/2D NMR experiments revealed six known and three previously unknown gymnemic acids as the key constituents of seven highly sensory-active fractions. Localized via a modified comparative taste dilution analysis (cTDA) and taste modulation probability (TMP) based screening techniques, a strong intrinsic bitterness was also observed for gymnemic acids. In addition, the suppressive effects of the most abundant acids on the response of the human sweet taste receptor to sucrose were verified by means of a functional hTAS1R2/hTAS1R3 sweet taste receptor assay. This in vitro screening revealed large differences in antisweet activity among the isolated compounds, where gymnemic acids XV and XIX showed the highest sweet suppressing activity. This broad-based molecular characterization of the sweet taste inhibiting activity of Gymnema sylvestre will enable further insight into the molecular basis of sweet taste modulation at the receptor level.

This study was aimed to phytochemically characterize and assess the antioxidant activities of 70% methanol extract and subsequent fractions of Cassia absus (L.) seeds, Gymnema sylvestre (L.) whole plant, Nigella sativa (L.) seeds, and Piper nigrum (L.) seeds. Powdered plant materials were extracted with 70% methanol and further fractionated with ethyl-acetate, n-butanol and the residual aqueous fraction. Phytochemical analysis was performed to detect different phytocompounds. Mineral compositions were quantified, and total phenolic and flavonoid contents were determined. The antioxidant potential of methanol extracts and fractions was assessed in vitro through estimating DPPH radical and superoxide anion scavenging activities and reducing power assay. Extraction yields ranging highest of N. sativa methanol extract (30.42�1.49%) and lowest of P. nigrum ethyl-acetate fraction (4.58�0.61%) were obtained. Results revealed that methanol extracts and fractions of selected plants contain phytocompounds such as alkaloids, flavonoids, phenols, glycosides, tannins, terpenoids, saponins, carbohydrates, fats and fixed oils. The mineral analysis showed considerable quantities of calcium (C. absus methanol extract: 372.454�3.633 mg/100g), magnesium (G. sylvestre methanol extract: 131.045�1.346 mg/100g), and zinc (N. sativa methanol extract: 36.019�0.284 mg/100 g) in all fractions while minor quantities of manganese, copper and cobalt were also found. Methanol extracts showed considerably higher total phenolic (N. sativa methanol extract: 179.71�2.14 mg GAE/g) and flavonoid (N. sativa methanol extract: 189.18�3.17 mg CE/g) contents compared to other fractions, and subsequently exhibited pronounced scavenging activities on DPPH* (N. sativa methanol extract: 23.8 �g/mL) and superoxide radicals (N. sativa methanol extract: 24.9 �g/mL) and had potent reductive abilities (N. sativa methanol extract: 1.123�0.038 O.D.). Conclusively, C. absus, G. sylvestre, N. sativa and P. nigrum possess significant nutritive properties and could be used as natural antioxidant sources to prevent oxidative stress-associated diseases.

Gymnemic acids (a group of triterpenoid saponins) found in Gymnema sylvestre (Retz.) R.Br. ex Sm. works as the main hypoglycaemic active components. These can be the potential active pharmaceutical ingredient (API) to be used by pharmaceutical industries in modern medicines against diabetes. The present study aims to investigate the effectiveness of sodium nitroprusside (SNP) treatment for enhancement of cell suspension culture biomass and to quantify the production of deacylgymnemic acid, gymnemagenin, gymnemic acid IV and gymnemic acid XVII contents. Callus was obtained from in vitro derived leaves of G. sylvestre on MS medium fortified with 3.0 mg/L 2, 4-d (2, 4-dichlorophenoxyacetic acid) and 2.0 mg/L Kn (Kinetin), and the same were used further to produce cell suspension cultures. Cell suspensions were exposed to different concentrations of SNP (5, 10, 20 and 40 μM) and data were collected at 20, 30 and 40 days. Out of the tested concentrations, 20 μM SNP had the highest level of cell culture growth (398.94 ± 8.32 g/L Fresh cell weight (FCW) and 40.00 ± 0.75 g/L Dry cell weight (DCW) on 40-day as compared to control (MS with 3.0 mg/L 2, 4-d + 2.0 mg/L Kn). High-performance liquid chromatography analysis showed that maximum accumulation of deacylgymnemic acid (5.51 mg/g DCW), gymnemagenin (2.80 mg/g DCW) and gymnemic acid XVII (2.08 mg/g DCW) in 20 μM SNP treatment which is (13.43, 13.86 and17.33 folds) higher than the respective control at 40 days exposure. This research suggests that G. sylvestre cell suspension culture with optimal SNP elicitation treatment could be used as a good strategy for the large-scale production of these secondary metabolites at the industrial level. This research suggests that Gymnema sylvestre cell suspension culture with SNP elicitation treatment could be used as a good strategy for the large-scale production of these secondary metabolites at the industrial level.

The results of antioxidant assays with Gymnema sylvestre leaf extracts revealed that methanol, acetone, and aqueous extracts possessed maximum DPPH (83, 83, and 75%) and ABTS scavenging potential (85, 71, and 82%). Chloroform possessed maximum total flavonoid (24.6 mg/100 ml) and total iron contents (435.3 ± 0.0125 mg FeSO4 E/G). The extracts of n-hexane, ethyl acetate, and chloroform of Gymnema sylvestre leaves displayed an IC50 value of 170.2, 44.4, 131.6 μg/ml, respectively in α-glucosidase inhibition assay. Methanol and aqueous extracts showed maximum inhibition of E. ammni (17 ± 2.0 and 19.6 ± 0.57 mm), E. coli (15.3 ± 0.57 and 17.6 ± 0.57 mm), and S. aureus (16.6 ± 1.52 and 19.3 ± 1.15 mm). It may be concluded that all potential effects of G. sylvestre leaf extracts were due to the presence of phytochemical constituents such as flavonoids, steroids, quinones, phenols, triterpenoids, tannins, alkaloids, and saponins. Present findings suggest that these extracts present a satisfactory source for the preparation of antioxidant and antidiabetic medicines.

Gymnema sylvestre and Combretum micranthum are well known for their ethno-medicinal uses in the northwest of Nigeria. In our recent study, we demonstrated the antidiabetic and antioxidant activities of the aqueous-me¬thanol extracts of the two plants and identified some potentially active compounds. The present study aimed to con¬duct molecular docking and ADME/drug-likeness screening of the identified potentially active candidate com¬pounds from aqueous-methanol extracts of G. sylvestre and C. micranthum leaves by using in silico techniques. Mo¬lecular docking of compounds on target proteins (α-amylase, α-glucosidase, and phosphorylated insulin re¬ceptor tyrosine kinase) was performed using Molsoft ICM-pro 3.8-3. The physicochemical, ADME, and drug-like¬ness para¬meters were computed using the SwissADME online program. The result corroborated the antidiabetic activities of the plants with significant binding interactions between compounds A (2,2-dimethyl-3-[4-(acetyl¬oxy)phenyl]-4-ethyl-2H-1-benzopyran-7-ol acetate), D (9,13-di-cis-retinoic acid), E (4-hydroxycinnamic acid), F ((-)-11-hydroxy-9,10-dihydrojasmonic acid), G (colnelenic acid), H (glyinflanin A), I (6,8a-seco-6,8a-deoxy-5-oxo¬aver¬mectin “2a” aglycone), and J (3-deshydroxysappanol trimethyl ether) and at least one of the three target proteins. Four compounds, namely A (2,2-dimethyl-3-[4-(acetyloxy)phenyl]-4-ethyl-2H-1-benzopyran-7-ol acetate), E (4-hy¬droxy¬cinnamic acid), H (gly¬inflanin A), and J (3-deshydroxysappanol trimethyl ether), yielded the best docking sco¬res with respect to the target proteins, of which three (E (4-hydroxycinnamic acid), H (glyinflanin A), and J (3-deshydroxysappanol trimethyl ether)) were identified to have relatively optimal drug-likeness and medicinal che¬mistry characteristics. Thus, the present study concluded that these compounds may have contributed to the observed antidiabetic properties of these plants and can be investigated further as drugs or drug-like compound candidates.

Gymnemic acids are triterpenoid glycosides with gymnemagenin as common aglycone found in Gymnema sylvestre (Gurmar). G. sylvestre is often used in herbal formulations because of its beneficial acti...

Gymnema sylvestre (Retz.) R. Br. ex Schult (Asclepiadaceae) and Sclerocarya birrea (A. Rich) Hochst (Anacardiaceae) are two plants used in Burkina Faso in traditional medicine and in the form of phytomedicine in the treatment of diabetes. This study evaluated the effect of aqueous ethanolic extracts of leaves of Gymnema sylvestre and Sclerocarya birrea on glycemia. A phytochemical screening of the extracts obtained by successive exhaustion after maceration of the leaves was carried out. The effect of these extracts was tested on basal plasma glucose and oral tolerance glucose in mice. Saponosides, tannins, flavonoids, sterol and triterpene glycosides, reducing compounds and coumarinic derivatives were found in the leaves of both plants. Alkaloids were also detected in the leaves of G. sylvestre and anthocyanosides in the leaves of S. birrea. The aqueous ethanolic extracts from leaves of G. sylvestre, S. birrea or both in combination at 100 mg/kg body per weight did not have a significant hypoglycemic effect on basal plasma glucose but significantly reduced (p

Diabetes mellitus (DM) is a serious metabolic disorder with altered carbohydrate, fat, and protein metabolism. In the last four decades, India has emerged as an epicenter of the global diabetes mellitus pandemic. Rapid changes in the developmental scenario, demographic changes, and living style in the Indian subcontinent have led to the explosive increase in diabetes. Present research probes with ethanolic extract of Gymnema sylvestre (500 mg/kg.b.w) for treatment of hyperglycemia and related oxidative stress caused by Alloxan (100 mg/kg.b.wt), as a diabetogenic agent. 25 rats were included in the research divided into 5 groups, each containing 5 rats. Group 1 (normal rats), Group II (Diabetic rats (DM), Group III (DM+ treated for 10 days), Group IV (DM+20 days treated), Group V (DM+30 days treated). Blood samples and pancreatic tissues were collected at each interval of time. The blood sample was used for biochemical parameter and tissues were used for the anti-oxidant assay. Gymnema sylvestre extract (GSE) showed glucose-lowering property meanwhile, insulin secretion also increased as compared to Diabetic rats. Other tests like amylase, lipase, ALT, and AST also showed significant recovery after the extract administration. Oxidative stress was found in the Diabetic group, but after extract treatment concentration of superoxide dismutase, Glutathione-S-transferase, catalase, Glutathione peroxidase, Glutathione, and Total thiol was regained. Imbalance in serum electrolyte recovered and dysregulated hematological parameters due to stress and hyperglycemia showed convincing results. The finding suggests Gymnema sylvestre could be used as a hypoglycemic as well as an anti-oxidant agent in diabetes.

Type 2 diabetes is delineated by impaired metabolic flexibility, and intramyocellular lipid accumulation, causing insulin resistance, particularly in skeletal muscle by reducing insulin-stimulated glucose uptake. High-fat diet and high fructose (HFD and HF) administration in rodents bestows a model for hyperlipidemia, insulin resistance, and Type 2 diabetes. The current study is focused on elucidating the role of Gymnemic acid in combating hyperglycemia mediated oxidative stress and apoptotic events in the skeletal muscle of HFD and HF induced Type 2 diabetes in Wistar albino rats by boosting antioxidant defense system. Gymnemic acid, a saponin of triterpene glycoside contained in leaves of Gymnema Sylvestre, has potent anti-diabetic properties. Treatment with Gymnemic acid restored the antioxidant status (Gpx, SOD, CAT, GR, Vit C & Vit E) with significant (p

Gymnema sylvestre is a commonly used herb in Ayurvedic medicine. The demand for its extracts in the commercial and pharmaceutical fields has been steadily increasing in recent years. Its extracts are used to treat various ailments as well as for their antimicrobial properties. This study has evaluated the antimicrobial effects of different G. sylvestre extracts and of eight triterpenes isolated from the most active extract on six bacterial poultry pathogens i.e. Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterobacter aerogenes. In particular, it has been evaluated the minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of all extracts and isolated triterpenes. Finally, the cytotoxicity activity of triterpenes was evaluated by MTT assay and their antioxidant activity in basal and oxidant conditions by DCFH-DA assay.

Introduction Gymnemagenin is the bioactive metabolite found in Gymnema sylvestre leaves and possesses different therapeutic potential. Due to its lower abundance and higher market potential, gymnemagenin was obtained from chemical conversion and bacterial biotransformation. Objective To obtain the probiotic-based fermentative conversion of gymnemic acid-enriched G. sylvestre leaf extract to gymnemagenin-containing nutraceuticals and its metabolites based chromatographic comparison. Material and methods Gymnema sylvestre leaves were extracted through soxhalation, and the extract was prepared and characterised. Gymnemic acid was fermented, separately, by Lactobacillus casei, Lactobacillus rhamnosus, Bifidobacterium bifidum, and by their mix co-culture. The fermented materials were analysed for their gymnemagenin content, antioxidant potential, antidiabetic potential, and metabolomics analysis. Results Extraction yielded about 35% w/w of raw plant material, and 8.5% was found to be as total saponin content. Extract at higher concentration (≥ 5%, w/v) significantly altered the growth behaviour of probiotics. High-performance thin-layer chromatography (HPTLC) based quantification of gymnemagenin revealed that a maximum increase of 95.5% gymnemagenin was found in extract incubated with B. bifidum followed by mix co-culture containing (B. bifidum, L. casei, and L. rhamnosus), L. casei, and L. rhamnosus. However, liquid chromatography mass spectrometry (LC-MS) analysis resulted in the identification of a total of 56 metabolites. Conclusion Chromatographically profiled, and probiotic-based fermented G. sylvestre leaves can be used as a potent nutraceutical for diabetes and other metabolic disorders.

Type 2 diabetes mellitus (T2DM) which is characterized by insulin resistance in muscle and adipose tissues is a major problem worldwide. Plant based medications are well known from ancient times for possessing antidiabetic properties. Amongst them, Gymnema sylvestre (GS) is one such antidiabetic medicinal plant which has been used traditionally over the years for the treatment of T2DM. The aim of the present study was to investigate the effect of triterpene glycoside (TG), an active fraction isolated from ethanolic extract of Gymnema sylvestre (EEGS) on a battery of targets; glucose transporter (GLUT- 4), peroxisome proliferator activator receptor gamma (PPAR-γ), adiponectin and leptin involved in glucose transport and metabolism. No cytotoxic effects were observed in treated cells up to 600 μg/ml of TG as measured by MTT and ROS assays. Elevation of GLUT-4 and PPAR-γ by TG in association with glucose transport supported the upregulation of glucose uptake at concentrations of 50 and 100 μg/ml respectively. Additionally, TG showed higher expression of adiponectin and leptin, confirming the favorable pharmacological effect of TG on insulin resistance. The results were comparable to the known antidiabetic drug pioglitazone and commercial standard DAG. Thus TG could be considered as a safe nutraceutical candidate/functional phytoingredient in amelioration of insulin resistance.

The major class of bioactive metabolites in Gymnema sylvestre, a popular Ayurvedic medicinal plant for the treatment of diabetes mellitus, is oleanane triterpenoids. In this study, a targeted, biosynthesis-inspired approach using UHPLC-qTOF/MS was implemented to elucidate the whole chemical profile of this plant for the standardization of the Vietnamese G. sylvestre variety. The known compounds were first determined to identify the building blocks of the biosynthetic intermediates and the construction rules for synthesizing oleanane triterpenoids in the plant. These blocks were recombined to build a virtual library of all reasonable compounds consistent with the deduced construction rules. Various techniques, including relative mass defect filtering, multiple key ion analysis, mass fragmentation analysis, and comparison with standard references, were applied to determine the presence of these predicted compounds. Conventional isolation and structure elucidation of six of the new compounds were carried out to identify the new building blocks and validate the assignments. Consequently, 119 peaks were quickly assigned to oleanane triterpenoids, and among them, 77 peaks were predicted to be new compounds based on their molecular formulas and mass fragmentation patterns. All the identified metabolites were then classified into different layers to analyze their logical relationships, and a multilayered chemical profile of the oleanane triterpenoids was constructed. This new approach is expected to be practical for characterizing structures of modular secondary metabolites, such as triterpenoid saponins, and for proposing biosynthetic relationships among compounds of the same class of metabolites in medicinal plants.

This study was aimed to assess the antidiabetic and antioxidant activity of starch nanoparticles (StNPs) synthesized by green synthesis through in vitro model. Several organic solvents were used for the extraction of active compounds from Gymnema sylvestre. The methanolic extract was used for the synthesis of StNPs from dried potato starch. The characterization studies such as GC–MS, FT-IR, SEM, EDS and XRD were performed to analyze the sample. The StNPs were found to be ellipsoidal in nature with the average particle size of 19.8 nm. The StNPs showed highest DPPH radical scavenging activity with 74.41 ± 0.54% at 100 µg/mL concentration. Besides, the IC50 values were found to be 66.69 µg/mL and 61.99 µg/mL for the StNPs and standard (ascorbic acid), respectively. The StNPs showed the highest metal ion chelating activity of 66.71 ± 0.34% at a concentration of 100 µg/mL. The highest reducing power of StNPs was found to be 0.385 ± 0.002 at 100 µg/mL. Moreover, in vitro antidiabetic activity was studied using alpha-amylase inhibition assay and the highest inhibition activity of StNPs was 58.56 ± 0.44% at a concentration of 100 µg/mL. The present study provided preliminary evidence indicated that the StNPs synthesized using methanolic extract of G. sylvestre had potential activity against diabetes.

Diabetes is a metabolic disorder which is characterised by high levels of blood glucose. Most of the oral drugs available today for the treatment of diabetes are associated with various side-effects. Herbal medicines are considered relatively safer alternatives and Gymnema sylvestre (GS) is one such known traditional medicinal plant widely used for the treatment of diabetes. In our previous work, we isolated active triterpene glycosides (TG) from Gymnema sylvestre (GS) and screened for yeast α-glucosidase inhibitory activity in vitro. The present study aims to use in silico techniques to understand and predict the inhibitory role of the isolated triterpene glycosides (TG); Gymnemic acid I, IV, VII and gymnemagenin against disaccharidase enzymes. enzyme kinetic analysis using Lineweaver-Burk plot indicated that TG competitively inhibited yeast α-glucosidase at IC50 concentration with Ki 0.0028 μM. TG also exhibited significant inhibitory activity against mammalian sucrase and maltase respectively, compared to control. Practical applications The molecular docking simulation reveals that TG is capable of docking well with crystallographic structures of the selected enzyme targets. Inhibition of α-glucosidases could delay the absorption of glucose in the blood during post-meal digestion. Thus the current study highlights the dietary intervention of TG towards the selected enzyme targets, thus making TG a potential nutraceutical candidate towards management of blood glucose., Gymnema sylvestre; Antidiabetic; in silico docking; Dissacharidases; Inhibition.

Diabetes represents a major health problem, involving a severe imbalance of blood sugar levels, which can disturb the nerves, eyes, kidneys, and other organs. Diabes management involves several synthetic drugs focused on improving insulin sensitivity, increasing insulin production, and decreasing blood glucose levels, but with unclear molecular mechanisms and severe side effects. Natural chemicals extracted from several plants such as Gymnema sylvestre, Momordica charantia or Ophiopogon planiscapus Niger have aroused great interest for their anti-diabetes activity, but also their hypolipidemic and anti-obesity activity. Here, we focused on the anti-diabetic activity of a few natural and synthetic compounds, in correlation with their pharmacokinetic/pharmacodynamic profiles, especially with their blood-brain barrier (BBB) permeability. We reviewed studies that used bioinformatics methods such as predicted BBB, molecular docking, molecular dynamics and quantitative structure-activity relationship (QSAR) to elucidate the proper action mechanisms of antidiabetic compounds. Currently, it is evident that BBB damage plays a significant role in diabetes disorders, but the molecular mechanisms are not clear. Here, we presented the efficacy of natural (gymnemic acids, quercetin, resveratrol) and synthetic (TAK-242, propofol, or APX3330) compounds in reducing diabetes symptoms and improving BBB dysfunctions. Bioinformatics tools can be helpful in the quest for chemical compounds with effective anti-diabetic activity that can enhance the druggability of molecular targets and provide a deeper understanding of diabetes mechanisms.

The present study was designed with the main aim to evaluate antimicrobial activity of aqueous leaf extract of Gymnema sylvestre against pathogenic microorganisms. Leaves of G. sylvestre was subjected to successive solvent extraction by continuous hot extraction (Soxhlet) with water. The extracts were diluted in dimethyl sulfoxide (DMSO) before testing the antimicrobial activity. The antimicrobial activity of extract for B. subtilis, K. aerogenus, S. aureus, E. coli, A. niger and P. chrysogenium was determined by agar well diffusion technique. The results of the present study revealed that aq. leaf extract of G. Sylvestre exhibited zones of inhibition at 100 mg/ml concentration. Aq. leaf extract of G. sylvestre exhibited zone of inhibition zone bacterial species like B. subtilis (10.55 mm), K. aerogenus (11.00 mm), S. aureus (8.50 mm), E. coli (12.50 mm), and against fungal species like A. niger (10.00 mm). In conclusion, present preliminary study delineated that the aqueous extract of G. sylvestre possesses considerable antimicrobial activities against B. subtilis, S. aureus, E. coli, K. aerogenes and A. niger. Hence, further experiments like isolation and purification of phytoactives of G. sylvestre responsible for antimicrobial activities could be recommended to carry out to further enhance the antimicrobial activities of phytoactives present in aq. leaf extract of G. sylvestre.

The brain is a vital organ that requires a constant blood supply. Stroke occurs when the blood supply to specific parts of the brain is reduced; diabetes is an autonomous risk factor for stroke. The present study aimed to investigate the potential vascular protective effect of gymnemic acid (GM) by assessing the morphological changes of microvasculature, along with VEGFA and angiopoietin-1 (Ang-1) protein expression in the brains of diabetic rats. Rats were divided into five groups, including control, gymnemic control rats (CGM), rats that were rendered diabetic by single injection of 60 mg/kg streptozotocin (STZ), diabetic rats treated with 400 mg/kg GM (STZ + GM) and diabetic rats treated with 4 mg/kg glibenclamide (GL; STZ + GL). After 8 weeks, brain tissues were collected to examine the three-dimensional morphology of the anterior cerebral arteries by vascular corrosion casting. Western blotting was performed to determine VEGFA and Ang-1 expression. Cerebral arteries, arterioles and capillaries were depicted the diameter, thickness and collagen accumulation of the wall, and the results demonstrated narrow diameters, thickened walls and collagen accumulation in the STZ group. After receiving GM, the histopathological changes were similar to that of the control group. Through vascular corrosion casting and microscopy, signs of vessel restoration and improvement were exhibited by increased diameters, and healthy and nourished arterioles and capillaries following treatment with GM. Furthermore, VEGF expression and Ang-1 secretion decreased in the STZ + GM group compared with STZ rats. The results of the present study revealed that GM treatment decreased blood vessel damage in the brain, suggesting that it may be used as a therapeutic target for the treatment of diabetes.

Background One of the major characteristics of Diabetes Mellitus (DM) is high blood glucose levels and impairment of insulin production, which can lead to serious complications, so the main aim of treating patients with diabetes, is to maintain normal levels of glycaemia control. With the adverse effects and limitations of the existing drugs, scientists have been in search for safer and more efficient and affordable alternative treatments. In this backdrop, search for a new generation of antidiabetic drugs is a priority in recent years. Purpose Natural products base drugs were used in traditional systems of medicine for diabetes. The introduction of drugs based on natural products is usually considered to be safer, cheaper, easily available and sometimes more efficacious than purely synthetic ones. In addition, the synergetic effect of the constituent agents could be better than a single agent acting alone. Accordingly, the aim of the present study was to develop a phytochemical formulation including bioavailable curcuminoids, extracts of Gymnema sylvestre, Emblica officinalis and Salacia reticulata based on traditional knowledge and to evaluate its anti-hyperglycemic and antioxidant activities. Methods The phytochemical formulation was prepared by using encapsulation technology and the bioactive components were estimated using UPLC. Physical parameters, total phenolic and flavonoid content, antioxidant (DPPH, FRAP, SOD scavenging activity), α-amylase inhibition and blood glucose lowering activity in rats were also evaluated. Results Oral supplementation at a dosage of 200 mg/kg and 400 mg/kg of phytochemical formulation for a duration of 21 days resulted in a 77.8% and 76.1% reduction in the blood glucose level. The total flavonoid content of 42.92 ± 0.028% QE, DPPH activity showed an IC50 of 93.59 ± 0.88 µg/mL, superoxide radical scavenging activity showed an IC50 of 45.71 ± 0.17 μg/ml, α-amylase inhibitory activity exhibited IC50 value of 1053 ± 1.41 µg/mL all showed promising results for the efficacy of the formulation. Conclusion Based on the results, the novel phytochemical formulation has potent antidiabetic and antioxidant efficacy, and which can be a promising candidate for the development of new generation antidiabetic drugs.

Gymnema sylvestre (Madhunashini) is one of the most important medicinal plants used as a crude drug for its preventive and therapeutic properties. Among other constituents of Gymnema, gymnemic acid is a major component responsible for biological and pharmacological actions. The present study deals with the influence of different media strength and initial medium pH on the growth of hairy roots and gymnemic acid production from Gymnema sylvestre. Higher strength of the media (1.5X) favoured the biomass production (114.64 g/L FW and 12.63 g/L DW) and gymnemic acid content (11.7 mg/g DW) in the tested range of 0.25, 0.50, 0.75, 1.0, 1.5 and 2.0 X strength. Among the different hydrogen ion concentration (pH) of 4.0, 4.5, 5.0, 5.5, 5.8, 6.0 and 6.5, initial medium pH of 6.0 favoured the biomass production (102.41 g/L FW and 11.52 g/L DW) and medium pH of 5.8 favoured the gymnemic acid production (11.30 mg/g DW).

Inflammatory cytokines such as interleukin-1β, TNF-α, and interferon-γ are known to be involved in mediating β-cells death in diabetes mellitus (DM). Thus, protecting from β-cells death in patients with DM may be a useful target in alleviating symptoms of hyperglycemia. Traditional plant-based remedies have been used to treat DM for many centuries and may play a role in protecting β-cell from death. An example of these remedies is Gymnema sylvestre (GS) extract. In this study, we investigated the effect of this plant extract on β-cells apoptosis. Om Santal Adivasi (OSA®) maintained cell membrane integrity in MIN6 cells and mouse islets. Om Santal Adivasi significantly protected MIN6 cells and mouse islets from cytokine-induced apoptosis. In the presence of cytokines, OSA® significantly reduced the expression and activity of caspase-3. The antiapoptotic effect of OSA® as shown by microarray analysis is largely mediated by activating pathways involved in cell survival (mainly casein kinase II pathway) and the free radical scavenger system (specifically superoxide dismutase and catalase). This study indicates that the GS isolate OSA® protects against cytokine-induced apoptosis of β-cells by increasing the expression of cell survival pathways and free radical scavenger system.

A mixture of gymnemic acids was precipitated from the water extract of leaves of Gymnema sylvestre (Retz.) R.Br. ex Sm. (Asclepiadaceae) by acidification with 2 N H2SO4. The chromatographic separation of the mixture afforded five new gymnemic acids (1-5). The compounds were characterized as Δ15 oleanane glycosides on the basis of extensive spectral data analysis. The compounds (1-5) showed dose dependent inhibition of α-glucosidase, which was found to be comparable to acarbose (IC50 95 μg/ml). Maximum inhibition was achieved with compound 4 (IC50 57 μg/ml) followed by 3 (IC50 62 μg/ml), 1 (IC50 80 μg/ml), 2 (IC50 120 μg/ml) and 5 (IC50 128 μg/ml). The results revealed that the overall pattern of hydroxyl and acyl substitutions of compounds affected their inhibitory activity. In oral sucrose tolerance test, pre-treatment with crude gymnemic acid mixture and isolated compounds 1 and 4 at a dose of 10 mg/Kg b.w. significantly blunted the effect of sucrose challenge in mice. Based on these results, the antihyperglycemic effect of G. sylvestre can be, at least partly, attributed to the inhibition of α-glucosidase by its gymnemic acids. The current study provides relatively more direct evidence explaining the effectiveness of G. sylvestre against hyperglycemia.

MicroRNAs (miRNAs) are single-stranded, non-coding, small (~ 22 nt) RNAs that regulate mRNA targets in plants and animals. Gymnema sylvestre (Retz.) is an important medicinal plant that lacks genomic as well as transcriptomic information. Here, to identify homologous miRNAs, we screened 6028 unique known plant miRNAs against 272,161 unigenes of G. sylvestre (Retz.) generated by paired-end deep transcriptome sequencing. We utilized 76 aligned unigenes for extracting the precursor sequences in G. sylvestre (Retz.) and identified 16 potential candidate miRNAs belonging to 12 miRNA families. The mean minimal folding free energy index (MFEI) value of these 16 predicted miRNAs was − 0.966, ranging from − 0.653 to − 2.37, while the G + C% content varied between 27.3 and 61.9%. Nucleotide composition analysis revealed that cytosine was the dominant nucleotide in mature miRNAs (26.3%), while uracil was the next most prevalent nucleotide (25.7%), followed by guanine (24.3%) and adenine (23.7%). In most cases (81%), the first position of the 5′ end was occupied by uracil in the identified mature G. sylvestre (Retz.) miRNAs. Differential expression of target unigenes revealed that, as compared to leaf tissue, a total 16 and 12 target unigenes were differentially expressed in flower and fruit tissues, respectively. Among the differentially expressed target unigenes were Auxin Response Factors 17-like, Copia-type polyprotein Phytoene synthase 2, as well as several encoding unnamed, predicted, uncharacterized, and/or hypothetical proteins. After detailed prediction of miRNAs and their corresponding target unigenes, we report for the first time a total of 13 miRNA and 213 corresponding target unigenes in G. sylvestre (Retz.).

Objective: The present study aims to determine the antioxidant properties and phytochemical screening of Gymnema sylvestre plant. Materials and Methods: The qualitative and quantitative analyses were carried out for the methanol extract using standard procedures. The antioxidant activities were carried out by DPPH free radical, OH- radical, H2O2 radical, O2 - radical and phosphomolybdenum reduction assay. Results: The leaves of G. sylvestre methanol extract showed good radical scavenging as well as reducing power activities. The total phenolic and flavonoid content were 19.87 ± 0.32 mg/g and 2.65 ± 0.12 mg/g respectively. Conclusion: The methanol extract of leaves of G. sylvestre possesses significant antioxidant activities.

Background Prediabetes describes a state of hyperglycemia outside of normal limits that does not meet the criteria for diabetes diagnosis, is generally symptomless, and affects an estimated 38% of adults in the United States. Prediabetes typically precedes the diagnosis of type 2 diabetes, which accounts for increased morbidity and mortality. Although the use of dietary and herbal supplements is popular worldwide, and a variety of single herbal medicines have been examined for glycemic management, the potential of increasingly common polyherbal formulations to return glycemic parameters to normal ranges among adults with prediabetes remains largely unexplored. The purpose of this study is to evaluate the efficacy of a commercially available, polyherbal dietary supplement on glycemic and lipid parameters in prediabetic individuals. Methods In this multi-site, double-blinded, randomized controlled clinical trial, 40 participants with prediabetes will be randomized to either a daily oral polyherbal dietary supplement (GlucoSupreme™ Herbal; Designs for Health®, Suffield, CT, USA; containing cinnamon bark (Cinnamomum cassia), banaba leaf (Lagerstroemia speciosa standardized to 1% corosolic acid), kudzu root (Pueraria lobata standardized to 40% isoflavones), fenugreek seed (Trigonella foenum-graceum standardized to 60% saponins), gymnema leaf (Gymnema sylvestre standardized to 25% gymnemic acid), American ginseng root (Panax quinquefolius standardized to 5% ginsenosides), and berberine HCl derived from bark (Berberis aristata)) or placebo for 12 weeks. Short-, medium-, and comparatively long-term markers of glycemic control (blood glucose and fasting insulin, fructosamine, and glycated hemoglobin/A1c, respectively), and other glycemic parameters (GlycoMark, β-cell function, and insulin sensitivity/resistance) will be obtained. Lipid profile (total cholesterol, LDL, HDL, and triglycerides), inflammation (hs-CRP), progression to type 2 diabetes mellitus, as well as safety indices (ALT, AST) will be obtained. An intention-to-treat analysis will be used to assess changes in study outcomes. Discussion Treatment options for adults with prediabetes are currently limited. This study aims to evaluate the safety and efficacy of a commercially available dietary supplement in the popular, but as yet insufficiently studied, category of polyherbal formulas for the management of glycemic parameters and other biomarkers associated with prediabetes. Trial registration ClinicalTrials.gov, ID: NCT03388762. Retrospectively registered on 4 January 2018. Electronic supplementary material The online version of this article (10.1186/s13063-018-3032-6) contains supplementary material, which is available to authorized users.

To study the biological fabrication and characterization of zinc oxide nanoparticles (ZnO NPs) using Gymnema sylvestre and their toxicity to breast cancer cells MCF-7.In the existing work, ZnO NPs were synthesized using leaf extract of the Indian medicinal plant Gymnema sylvestre and it was characterized by Particle size, Zeta potential, FT-IR, XRD and SEM analyses.This ZnO NPs to have potentially validated anticancer role in breast cancer cells MCF-7 in vitro approach.The plant-based synthesized ZnO NPs were evaluated against the inhibitory role on breast cancer cell lines. We significantly observed that ZnO-NPs induce efficient toxicity of MCF-7 cells by increasing ROS, mitochondrion membrane damage and apoptotic morphological alterations. These results stated that ZnO-NP induces Bax and Caspases and down-regulates Bcl-2 proteins in MCF-7 cells. Thus, the biologically synthesized ZnO NPs were identified as good performance to inhibit breast cancer cell growth even at low concentrations.

Diabetes and diabetes-related complications remain a major health issue in the United States and around the world. Despite the discovery and clinical use of modern antidiabetic medicines, 387 million people were living with diabetes in 2014, and this number is expected to grow to 592 million by 2035. To fight this problem, many patients use complementary and alternative medicines to supplement standard therapy. The reasons for this include low cost, easy availability, and the presumption of relatively better safety of nutraceuticals. Over the past three decades, interest in natural solutions to health ailments has grown dramatically across the world, including the United States, and the trend appears to be continuing. In view of such extensive use of nutraceuticals, it is extremely important that adequate and authentic scientific information about their efficacy and safety is available to the public and healthcare professionals in a format similar to that which is available for pharmaceuticals. This chapter provides efficacy and safety information for some of the most common nutraceuticals used as supplements for the management of type II diabetes. Based on a review of the literature, information is presented in an easy-to-follow format with sections included for general introductory overview, bioactive component(s), preclinical efficacy, clinical efficacy, mechanism(s) of action, and margins of safety with respect to the dose suggested for the supplement. Also, the potential for adverse effects related to plant component(s) that may be present, but not desired for efficacy, is discussed where applicable. Steps to mitigate such adverse effects are also discussed. The nutraceuticals discussed in this chapter include cinnamon, fenugreek, Momordica charantia (bitter melon), Gymnema sylvestre (Gur-Mar), ginger (gingerol and shogaol), and others. In addition to herbal nutraceuticals, the beneficial roles of vitamin D, trivalent chromium, and some other compounds used in managing hyperglycemia are discussed.

Gymnema sylvestre, a perennial woody climber popular for its antidiabetic property and its leaves are widely recommended to use in the traditional system of medicine. The oleander aphid, Aphis nerii is a major pest of G. sylvestre from October to March in central India. The present study was carried out to evaluate the efficacy of different biorational insecticides like Azadiractin 1% EC (10000ppm), aqueous leaf extract (5%) of Kalmegh or the Creat, King of Bitters (Andrographis paniculata) and Indian bael or Golden apple (Aegle marmelos), insect growth regulator (Buprofezin 25% SC), commercial entomopathogenic formulations like Beauveria bassiana (2×109 spores/ml), Metarhizium anisopliae (2×109 spores/ml), Lecanicillium muscarium (Verticillium lecanii; 2×109 spores/ml) on A. nerii under laboratory and field condition during 2019 and 2020. It was discovered that the leaf spray method was superior to the leaf dipping method. In the leaf spray method, hundred percent mortality of A. nerii was recorded with the application of azadirachtin post 72 HAT and efficacy of B. bassiana, M. anisopliae and L. muscarium were statistically in the same group during both year of study. However, in the leaf dip method, hundred percent mortality of A. nerii was recorded with the treatment of azadirachtin post 96 HAR. In both bioassay methods, the lowest population reduction and mortality were observed in bael followed by kalmegh plant extract under laboratory conditions. On the tenth days of treatment, azadirachtin showed hundred percent reduction in the aphid population with hundred percent efficacy. The entomopathogenic fungi like M. anisopliae (85.4%, 87.8%) and B. bassiana (78.3%, 83.8%) were equally effective in reducing A. nerii population with the efficacy of (87.4%, 90.4%) and (81.2%, 87.2%) under field condition during 2019 and 2020 respectively.

Palladium nanoparticles (PdNPs) were synthesised using a microwave technique using Gymnema sylvestre (GSE) leaf extract. PdNPs were tailored to different PdCl2 and plant extract concentrations. Using XRD the crystalline existence of GSE-PdNPs has been established, confirming the formation of face-centered cubic structure. UV–Vis spectra of PdNPs confirmed the reduction of Pd2+ to Pd0. The FTIR spectra indicate the existence of functional groups which are responsible for nanoparticles reduction and progression. The SEM discloses quasi-sphere nanoparticles without agglomeration or aggregation which TEM confirms further. The reduction of Cr (VI) was performed with PdNPs (10 mg/L) and achieved a reduction of 96% within 30 min. In order to investigate the efficient reduction of chromium from Cr (VI) to Cr (III), different reaction system parameters have been optimised.

The whole world is entangled by the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), people are dying in thousands each day, and without an actual medication, it seems not possible for the bringing this global health crisis to a stop. Natural products have been in constant use since ancient times and are proven by time to be effective. Crude extract or pure compounds isolated from medicinal plants and/or herbs such as Artemisia annua, Agastache rugosa, Astragalus membranaceus, Cassia alata, Ecklonia cava, Gymnema sylvestre, Glycyrrhizae uralensis, Houttuynia cordata, Lindera aggregata, Lycoris radiata, Mollugo cerviana, Polygonum multiflorum, Pyrrosia lingua, Saposhnikoviae divaricate, Tinospora cordifolia etc. have shown promising inhibitory effect against coronavirus. Several molecules, including acacetin, amentoflavone, allicin, blancoxanthone, curcumin, daidzein, diosmin, epigallocatechin-gallate, emodin, hesperidin, herbacetin, hirsutenone, iguesterin, jubanine G, kaempferol, lycorine, pectolinarin, phloroeckol, silvestrol, tanshinone I, taxifolin, rhoifolin, xanthoangelol E, zingerol etc. isolated from plants could also be potential drug candidates against COVID-19. Moreover, these could also show promising inhibitory effects against influenza-parainfluenza viruses, respiratory syncytial virus, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have reported 93 antiviral drug candidates which could be a potential area of research in drug discovery.

Many people suffering with diabetes mellitus with increased risk of complication which affects the qualityof day today life style this increases the mortality rate of the people. To reduce the people financial burdenand to prevent the side effects of diabetes mellitus, an extract of plant called Gymnemasylvestre’s showsa potential effect in reducing the sugar level.Gymnema leaves have the mixture of bioactive constituent’stri-terpenes, glycosides and saponin property which represents the antidiabetic property. Theleaves ofgymnema sylvestre are used in herbal medicinal preparation. Theleaves of Gymnema sylvestre contain bothantidiabetic and hypolipedemic properties. Here the review of such plant is discussed in this paper

This investigation aimed to study the effect of gymnema (Gymnema sylvestre) and sea grape (Coccoloba uvifera L.) on carbon tetrachloride (CcL4) induced hepatotoxicity in rats. Thirty male albino rats weighing 150±5g were divided into 6 equal groups (n=5 rats); one group kept as control negative, while the other 5 groups injected s/c by CcL4 in parrafin oil 50% V/V (2ml / kg b.wt.) twice a week for two weeks for liver intoxication incidence, one of them left as (C +ve) while the rest four groups orally administered using two doses 5 & 10% of gymnema and sea grape each. At the end of experimental period (45 days), blood samples were collected for serum separation to determine serum liver enzymes, total cholesterol, triglycerides, atherosclerosis index, lipoprotein fractions and kidney functions. The obtained results demonstrated that gymnema and sea grape at two doses 5 &10%, especially at high dose for each herb caused significant improvement in liver enzymes, lipid profiles, serum glucose and kidney functions in hepatotoxic rats. According to the results, gymnema and sea grape could improve the levels of liver enzymes, lipid profiles, glucose and kidney functions in CcL4 induced hepatotoxicity in rats.

Natural products derived from plants and microbes are a rich source of bioactive molecules. Prior to their use, the active molecules from complex extracts must be purified for downstream applications. There are various chromatographic methods available for this purpose yet not all labs can afford high performance methods and isolation from complex biological samples can be difficult. Here we demonstrate that preparative liquid-phase isoelectric focusing (IEF) can separate molecules, including small molecules and peptides from complex plant extracts, based on their isoelectric points (pI). We have used the method for complex biological sample fractionation and characterization. As a proof of concept, we fractionated a Gymnema sylvestre plant extract, isolating a family of terpenoid saponin small molecules and a peptide. We also demonstrated effective microbial protein separation using the Candida albicans fungus as a model system.

Diabetes mellitus is a growing public health concern and an increasing interest has been raised to search for new compounds with therapeutic effects on β-cells. There are chronic insulin resistance and loss of β-cell mass in the case of type-2 diabetes which covers about 90% of total diabetic patients. This work aims to critically review the protective and regenerative effects of various antidiabetic natural products on pancreatic β-cells. A thorough literature survey was conducted on the natural molecules and extracts having a protective, regenerative, and repairing effect on β-cells. The primary source of the literature was online scientific databases such as PubMed, Scopus, and Google Scholar. Besides, selected relevant textbooks were also consulted. Various natural molecules including berberine, curcumin, mangiferin, stevioside and capsaicin, and extracts obtained from the plants like Capsicum annum, Gymnema sylvestre, Stevia rebaudiana and Nymphaea stellate, were found to produce regenerative and anti-apoptosis effects on β-cells. These natural products were also found to increase insulin secretion by stimulating β-cells. The present review concluded that a large number of molecules and extracts, abundantly found in nature, possess antidiabetic effect via targeting β-cells. Further research is warranted to use these agents as a drug against diabetes.

Gymnema sylvestre (GS) is one of the herbal plant used since in ancient times. The present study aimed to assess bioactive compounds GS mainly gymnemic acids as potential inhibitors for COVID-19 against Mpro enzyme using a molecular docking study. The docking score observed between -53.4 to - 42.4 of all gymnemic acids and its derivatives. Molecular Dynamics (MD) simulation studies carried out at 100ns supported the stability of GS molecules within the binding pocket. RMSD score of less than 3.6. mainly, our results supported that these GS molecules bind to the domain I & II, and domain II-III linker of 3CLpro enzyme, suggesting its suitability as strong candidate for therapeutic against COVID-19.

Therapeutic potential of Gymnema sylvestre on diverse cell types is predominantly due to a variety of terpenoids and their derivatives. However, their bioavailability becomes limited due to poor solubility and lower lipophilic properties, provoking the search for novel membranotropic terpenoids and their mechanism of action. A terpenoid fraction purified from Gymnema sylvestre exhibited broad spectrum antimicrobial activity against both Gram positive and Gram negative bacteria with IC50 ˂ 0.1 mg/ml. Evaluation of its membranotropic effect in vitro on reconstituted model membrane revealed that the fraction induced flip-flop of fluorescent phospholipid analogs across the lipid bilayer. The terpenoid-induced lipid flipping was biphasic with a fast linear phase (rate constant (k1) = 3 to 5 S−1) and a second slow exponential phase (rate constant (k2) = (4 to 9) × 10−3 S−1). The lipid-flippase activity of the terpenoid fraction showed concentration and incubation-dependent cooperativity, indicating their lipophilic nature and membrane-destabilizing activity that facilitated lipid translocation. For the first time, our study reveals the flippase activity of a terpenoid fraction of Gymnema sylvestre that could be further explored for their membrane-mediated pharmacological properties.

Gymnema sylvestre, a medicinal plant, has been used in Indian ayurvedic traditional medicine for the treatment of diabetes. Phytochemical investigation of Gymnema sylvestre led to the isolation of five new pregnane glycosides, gymsylosides A&ndash, E (1&ndash, 5) and four known oleanane saponins, 3&beta, O-&beta, D-glucopyranosyl (1&rarr, 6)-&beta, D-glucopyranosyl oleanolic acid 28-O-&beta, D-glucopyranosyl ester (6), gymnemoside-W1 (7), 3&beta, D-xylopyranosyl-(1&rarr, D- glucopyranosyl-(1&rarr, D-glucopyranosyl ester (8), and alternoside XIX (9). Their structures were identified based on spectroscopic evidence and comparison with those reported in the literature. All compounds were evaluated for their &alpha, glucosidase and &alpha, amylase inhibitory activities. Compounds 2&ndash, 4 showed significant &alpha, amylase inhibitory activity, with IC50 values ranging from 113.0 to 176.2 &micro, M.