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Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. Methodology: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. Results: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. Conclusion: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects. [ABSTRACT FROM AUTHOR]

Medicinal plants are rich in biologically active phytoconstituents and therapeutic compounds that have wide applications in pharmaceutical industry. The ameliorative actions of such phytochemicals could be attributed to the presence of dietary fibre, detoxifying mediators, neuropharmacological agents, antioxidants, anticancer mediators, etc. In the present study, we investigated the in vivo antivenom potential of Gymnema sylvestre R. Br leaf extract (GSE)in experimental animal model. The study also investigated the antioxidant potential (in vitro) of GSE (aqueous and methanolic) along with qualitative phytochemical constituent tests. Phytochemical tests were performed by qualitative method to detect the presence of different phytoconstituents within the leaf. Different quantitative tests (DPPH scavenging, H2O2 scavenging, Ferric reducing activity) were performed. The IC50 value was determined from the different concentration. To detect the venom neutralization effects, in vitro PLA2 and in vivo lethality, haemorrhage, edema neutralization studies were performed. Aqueous and methanolic extracts of the leaf (400 mg/kg and 100 mg/kg body wt.) provided protection against the lethal dose of venom and showed a successful anti-hemorrhagic and edema neutralization activity against Daboia russelli venom (DRV). In vitro PLA2 neutralization activity of the leaf showed up to 3-fold protection. Methanolic extract exhibited the significant results in both qualitative phytochemical analysis as well as in vitro antioxidant studies. The results specify that the leaves of Gymnema sylvestre R.Br. possess antioxidant as well as antivenom potential and could act as a free radical inhibitor. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a serious metabolic condition characterized by high blood glucose levels due to inadequate insulin action or insulin resistance. It can impair various metabolic pathways in cellular metabolism, leading to significant long term effects. In the Ayurvedic system of medicine, leaves of Gymnema sylvestre (GS) have been traditionally utilized to manage diabetes. Aim of the study: This study aims is aimed to investigate the mechanism of action driven by the chemical constituents in potentially treating diabetes. Methods: Metabolite profiling of the methanolic extract from Gymnema sylvestre leaves (MLGS) was conducted using thin-layer chromatography (TLC), and ultraperformance-liquid chromatography-mass spectroscopy (UP-LCMS). Molecular Docking and MD simulations were carried out to investigate the interaction between selective phytoconstituents and the antidiabetic target, peroxisome proliferator-activated receptor (PPARγ). Results: MLGS demonstrated significant antioxidant activity, estimated using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), and with an IC50 of 103.73 μg/mL. Aditionally, MLGS also exhibited substantial inhibition of α-amylase and α-glucosidase, with an IC50 of 113.49 μg/mL and 127.40 μg/mL, respectively. Using TLC-MS-bioautography, two antioxidant metabolites and three α-amylase inhibitory metabolites were identified Quercetin was identified in both α-amylase and antioxidant prominent bands. Identified phytoconstituents, namely rutin and lupeol, exhibited favorable docking interactions with PPARγ. MD simulations results indicate that rutin creates a well-built protein-ligand complex, showed minor structural modifications, and could exhibit agonistic activity with PPARγ. This suggesting the potential of rutin as a druggable compound to treat diabetes. Conclusion: These findings suggest that MLGS is enriched with antidiabetic phytoconstituents, warranting further exploration through the isolation of antidiabetic metabolites and their testing in animal models.

This study investigated the chemical constituents, antioxidant potential, and in vitro and in silico antidiabetic activity of Gymnema sylvestre. Column chromatography and spectroscopic techniques identified twelve compounds from the methanol extract, including 4 sterols (1–4), 5 triterpenoids (5–9), and 3 flavonoids (10–12). The chemophenetic significance of all compounds was also investigated. The antioxidant capacity of the extract and compounds (1–4) was evaluated using FRAP and DPPH assays. The extract exhibited strong free radical scavenging activity (IC50 = 48.34 µg/mL), while compounds (1–4) displayed varying degrees of efficacy (IC50 = 98.30–286.13 µg/mL). The FRAP assay indicated significant reducing power for both extract and compounds (58.54, 47.61, 56.61, and 49.11 mg Eq.VitC/g for extract and compounds 1 & 2, 3, and 4, respectively). The antidiabetic potential was assessed through α-amylase and α-glucosidase enzyme inhibition assays. The crude extract demonstrated the most potent inhibition (IC50 = 218.46 and 57.42 µg/mL for α-glucosidase and α-amylase respectively) suggesting its potential for managing postprandial hyperglycaemia. In silico studies employed molecular docking and dynamics simulations to elucidate the interactions between identified compounds and α-amylase/α-glucosidase enzymes. The results revealed promising binding affinities between the compounds and target enzymes, with compound 6 demonstrating the highest predicted inhibitory activity with −10 kcal/mol and −9.1 kcal/mol for α-amylase and α-glucosidase, respectively. This study highlights the presence of diverse bioactive compounds in Gymnema sylvestre. The extract exhibits antioxidant properties and inhibits carbohydrate-digesting enzymes, suggesting its potential as a complementary therapeutic approach for managing hyperglycaemia associated with type 2 diabetes.

This article presents the findings of a study on the anti-hyperglycemic effects of three indigenous drugs: Momordica charantia, Gymnema sylvestre, and Piper betle. The study was conducted on rabbits and found that all three herbal extracts were effective in reducing fasting blood glucose levels. The results suggest that these indigenous drugs could be potential alternative treatments for hyperglycemia. The study also compared the effects of the herbal extracts to the commonly used drug glyburide and found them to be comparable. [Extracted from the article]

The main objective of this research was to perform Gymnema sylvestre (Asclepiadaceae) extract's phytochemical screening and identify its therapeutic potential. Using a Soxhlet apparatus, the powdered plant material was extracted using ethyl acetate. The preliminary phytochemical analysis confirmed the presence of alkaloids, flavonoids, phenols, glycosides, and steroids. Gas chromatography–mass spectroscopy analysis of the extract was performed and confirmed the presence of 11 compounds. As per the quantitative analysis, the extract exhibited a phenolic content of 948 µg gallic acid equivalent/g dry weight, a total flavonoid content of 398 µg quercetin equivalent/g dry weight, and an alkaloid content of 487 µg atropine equivalent/g dry weight. As per the in vitro cytotoxicity test using A549 cells, the IC50 (half-maximal inhibitory concentration) value for the extract was found to be 76.06 ± 1.26 µg/mL, indicating its cytotoxic effect on the cells. The ethyl acetate extract showed significant antibacterial efficacy, as evidenced by a zone of clearance measuring 3 mm against Escherichia coli and 6 mm against Bacillus subtilis. For anthelmintic activity, the earthworm paralysis time induced by G. sylvestre extract (10 mg/mL) was 28.13 ± 0.8 min, and the time of death was 68.21 ± 1.72 min. In comparison, the reference drug, piperazine citrate (10 mg/mL), caused paralysis in 22.18 ± 1.02 min and resulted in death at 66.22 ± 2.35 min. Similarly, the coagulation time was notably prolonged, with blood clot formation observed at 1 min and 40 s, at a concentration of 1 mg/mL, which underscores the potential anticoagulant or hemostatic modulation properties of G. sylvestre extract. The test extract showed good inhibition of alpha-amylase activity and exhibited an IC50 value of 15.59 µg/mL. The IC50 value for DPPH (2,2-diphenyl-1-picrylhydrazyl)-scavenging activity for the extract was 19.19 µg/mL. Based on the GCMS results, the compound 2,7-dimethyl-undecane was selected for its anticancer potential. Docking studies were conducted with the epidermal growth factor receptor (EGFR) protein, specifically the 5WB7 variant associated with lung cancer. The docking score was −4.5, indicating a potential interaction. Key interaction residues such as ASN328, VAL350, and THR358 were identified. Overall, this research provides valuable insights into the phytochemical composition and diverse biological activities of G. sylvestre extract, offering a foundation for further exploration of its medicinal and pharmacological potential. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is characterized by high blood glucose levels and lipid alterations. Besides pharmacological treatment, lifestyle modifications and nutraceuticals can be used to manage glucose and lipid profiles, which is crucial for preventing, or avoiding, serious consequences associated with the condition. This randomized controlled clinical trial on 75 patients with T2DM evaluated the effects of a combination of myo-inositol and d-chiro-inositol (40:1), α-lactalbumin, Gymnema sylvestre, and zinc on glucose and lipid profile. The intention-to-treat analysis displayed no significant differences in glucose parameters between the groups; however, the study group displayed reduced levels of total cholesterol (p = 0.01) and LDL (p = 0.03) after 3 months of supplementation. A subgroup analysis involving patients who did not modify their antidiabetic therapy, after 6 months displayed improved levels of total cholesterol (p = 0.03) and LDL (p = 0.04) in the study group versus placebo, along with a greater body weight reduction (p = 0.03) after 3 months. Furthermore, within the study group, levels of HDL (p = 0.03) and triglycerides (p = 0.04) improved after 3 months. These findings support supplementation with myo-inositol and d-chiro-inositol (40:1), α-lactalbumin, Gymnema sylvestre, and zinc as an adjuvant and safe strategy to manage the lipid profiles of patients with T2DM. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), an infectious disease caused by multi-drug resistant Mycobacterium tuberculosis (Mtb), has been a global health concern. Mtb affects over a third of the world’s population, causing two million deaths annually due to its dormancy and propensity to spread infection during this period. Resuscitation-promoting factor B (RpfB) plays a pivotal role in the growth of Mtb during dormant periods, making it a critical target for eliminating Mtb and curing TB. Gymnema sylvestre is a famous medicinal plant with several medicinal properties, including antimicrobial activity; however, the therapeutic potential of the various reported metabolites of this plant against Mtb has not yet been explored. The aim of this study was to explore the reported natural products of G. sylvestre against the RpfB of the Mtb. A total of 131 reported secondary metabolites of this plant were collected and virtually screened against the RpfB. We particularly targeted the Glu292 residue of RpfB as it is crucial for the catalysis of this protein. From our in-house library, 114 compounds showed a binding affinity higher than the standard drug. The binding stability of the top three lead compounds was further confirmed through MD simulation analysis. Drug likeness analyses indicated that the ten hits had zero violations of the Lipinski rule of five. In addition, analyses of pharmacokinetics, toxicity, and target prediction revealed that the top compounds are devoid of toxicity and do not affect human proteins. Additionally, they reflect multifaceted approach as anti-TB agents. Our selected hits not only exhibit molecular properties favoring physiological compatibility but also exhibit properties enhancing their potential efficacy as therapeutic candidates. The compounds investigated here are worthy of experimental validation for the discovery of novel treatments against TB. Further, this study also provides a promising avenue for research on the pharmacological potential of G. sylvestre. [ABSTRACT FROM AUTHOR]

The current study aimed to explore the anti‐diabetic effect of aqueous extracts of Gymnema sylvestre, Trigonella foenum‐graecum and mixture of both the plants in alloxan‐induced diabetic rabbits. A total of 30 rabbits were grouped into six equal groups as: normal control, diabetic control, diabetic treated with 300 mg/kg body weight (bw) G. sylvestre, diabetic treated with 300 mg/kg bw T. foenum‐graecum, diabetic treated with 300 mg/kg bw mixture of both the plants and diabetic treated with 500 mg/kg bw metformin for 4 weeks. Diabetes was induced to all the study group animals except normal control by intravenous administration of alloxan monohydrate (80 mg/kg bw). Blood glucose was measured by glucometer and other biochemical parameters were determined through various kit methods. Serum insulin was measured through ELISA kit method. Results showed that both the plants and metformin significantly (p <.05) decreased the fasting blood glucose. Hypoglycemic activity of aqueous extract of G. sylvestre and metformin was found slightly higher than aqueous extract of T. foenum‐graecum and the mixture of both the plants. However, a significant (p <.05) rise in insulin secretion was observed in studied plants extract treated rabbits. Serum urea, creatinine, and liver enzymes were found reduced significantly (p <.05) in treated rabbits whereas packed cell volume was also returned to normal in treated animals as compared to control group. The study concluded that G. sylvestre and T. foenum‐graecum extracts have comparable effects with metformin in normalizing the blood glucose level and have more pronounced effect than metformin in restoring the serum biochemical parameters to normal levels. Hence, these plants may be the good alternative medicine in managing the diabetes mellitus. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is described as a metabolic disorder, which was characterised by high blood glucose levels, which were resulted due to insufficient insulin secretion. There were major complications related to diabetes mellitus. To evaluate the antidiabetic effect of Gymnema sylvestre Zinc Oxide Nanoparticles. Streptozotocin (STZ) of 50mg/kg is used for the induction of diabetes into Wistar rats. The animals were divided into 6 groups. Group-I represented as Control; Group-II represented as diabetic control (STZ); Group-III represented as 5 mg/kg body weight of glibenclamide + diabetes; Group-IV represented as Gymnema sylvestre extract + diabetes; Group-V represented as 100 µg Gymnema sylvestre Zinc Oxide nanoparticles + diabetes; group-6-Gymnema sylvestre Zinc Oxide Nanoparticles 200 µg + diabetes. The GsZnONPs were inspected to morphological properties using UV spectrophotometer and FTIR. The GsZnONPs shown characterization peak at 300nm. The study has shown that GsZnONPs treated group has shown reduced glucose concentration. The histopathological alterations were also studied in all experimental groups. The pathology results of GsZnONPs (200 µg) group has shown the regeneration of islets cells of pancreas. The research study has proved that Gymnema sylvestre ZnO NPs exerts antidiabetic properties. [ABSTRACT FROM AUTHOR]

Background: Gymnema sylvestre R.Br. is famous medicinal plant among diabetics for its gymnemic acid content. It also contains flavonoids, which are an essential component in various other products. Though some molecular information on the biosynthesis of gymnemic acid, polyoxypregnane, micro RNAs and photosynthetic efficiency is available, there is no gene level information available on the biosynthesis of flavonoids in this plant. RNA was extracted from winter-collected Gymnema sylvestre leaves and cDNA libraries were prepared and used for next generation sequencing. De novo transcriptome assembly were prepared and Coding DNA Sequences (CDS) of 13 major genes involved in flavonoids biosynthesis were identified from transcriptome data. Phenylalanine ammonia lyase gene containing full-length CDS was employed for in silico protein modelling and subsequent quality assessment. These models were then compared against publicly available databases. To confirm the identification of these genes, a similarity search was conducted using the NCBI BLAST tool. Results: Therefore, in the present study, an effort has been made to provide molecular insights into flavonoid biosynthesis pathway by examining the expressed transcripts in G.sylvestre. Gene sequences of total thirteen major genes viz., phenylalanine ammonia lyase, 4-coumarate CoA ligase, cinnamic acid 4-hydroxylase, shikimate O-hydroxycinnamoyl transferase, coumaroyl quinate (coumaroyl shikimate) 3′-monooxygenase, caffeoyl-CoA O-methyltransferase, chalcone synthase, chalcone isomerase, naringenin 3-dioxygenase, flavanol synthase, flavonoid 3′-monooxygenase, Flavanone 7-O-glucoside 2″-O-beta-L-rhyamnosyltransferase and leucoanthocyanidin dioxygenase were identified and a putative pathway of flavonoids biosynthesis has been illustrated based on transcriptome data. Conclusions: This transcriptome study has contributed gene-level insights into the biosynthesis of flavonoids in plants as a whole and represents the first report within a non-model plant, Gymnema sylvestre perticullarly.

Background: Gymnema sylvestre (Retz.) R.Br. ex Sm. is a medicinal herb used in Ayurvedic medicine to treat diabetes. Through promoting obesity and lowering insulin resistance, anti-diabetic herbs may be more effective in treating polycystic ovarian syndrome (PCOS). Recently, YES‐associated protein-1 gene (YAP1) has been reported to be a new susceptibility gene for PCOS in clinical studies. Hence, we evaluated the effects of hydroalcoholic G. sylvestre extract on regulating the YAP1 protein in PCOS mice injected with dehydroepiandrosterone (DHEA) by examining mitochondrial alterations in the ovary. Materials and methods: The DHEA-induced PCOS female C57BL6/J mice were treated with three doses of G. sylvestre and standard drug metformin. Study parameters include body weight gain, estrus cyclicity, glucose tolerance testing, serum hormone levels, lipid profiles, liver enzymes, and inflammatory cytokines. Electron microscopy, histological, and immuno-histochemical (IHC) analyses were used to determine the morphological changes of the ovary. IHC analysis was used to assess the expression of the YAP1 protein. Results: As compared with the control group, the G. sylvestre-treated groups showed decreased obesity, estrus irregularity, improved glucose metabolism, reduced AST and ALT values, hormonal abnormalities, and inflammatory cytokines (IL-6, IL-17, IL-23, TNF-α). Interestingly, metformin and G. sylvestre therapy reduced YAP1-positive cells in the ovary of DHEA-induced PCOS mice. Conclusion: These findings suggest that a higher concentration of G. sylvestre extract at 500 mg/kg improved mitochondrial architecture in the PCOS ovary via modulating the key pathogenic protein of PCOS, YAP1.

Abstract Gymnema sylvestre (GS) has been traditionally used to treat diabetes mellitus (DM) and consumed as both food and medicine. The present work aimed to reveal the arresting hypoglycemic properties of GS leaves on type 2 DM (T2DM) rats meditated by gut microbiota pathway. After administration for 30 days, GS treatment observably improved the abnormal fasting blood glucose (FBG) levels, lipid profiles, and the glucose tolerance of the T2DM rats in a dose‐dependent manner. Furthermore, GS treatment reversibly restored the gut microbiota diversities in the T2DM rats based on the decreased Firmicute abundance and boosted Bacteroidetes abundance and Firmicutes/Bacteroidetes ratio. Particularly, the KEGG pathway suggested that GS treatment strongly interfered with the glucose metabolism processes, such as the glycolysis from glucose 6‐phosphate and glucose, along with the changes in the relative abundances of the beneficial bacteria of Clostridium, Lactobacillus, and Bacteroides. In addition, the GS treatment dramatically promoted the contents of the acetic acid, the total short‐chain fatty acids in the T2DM rat feces. This study showcased the remarkable amelioration of GS on the metabolic disorders of blood glucose and lipids via the regulation of gut microbiota in T2DM rats, which could offer a new mechanism of GS as a potential natural antidiabetic food supplement for T2DM.

Abstract Background In spite of the increased prevalence of Polycystic Ovary Syndrome in bilateral ovaries (PCOS) in females globally (~ 20%), the rate of decisive treatment is limited due to late and invasive diagnostics and the unavailability of stand-alone drugs against phenotypic symptoms associated with PCOS. This study aims at unravelling molecular mechanisms allied with this disorder and identifying genes and pathways that are altered causing PCOS as a pre-requisite need. Furthermore, this study intends at assessing the therapeutic potentials of Gymnema sylvestre phytocompounds mainly triterpene saponins against targeted proteins and helps in seeking exemplar drug candidates. The study is designed in 2 major parts—firstly identifying key proteins involved in pathophysiology by tracing back the deregulated genes in mRNA expression profiles of PCOS Patients obtained from GEO datasets database further compared and analysed by GEO2R Analyzer and significantly deregulated genes were subjected to PPI network, KEGG and GO analysis using STRING and ShinyGO tools. The second half of the study involved molecular docking its visualisation and in silico pharmacological analysis of imminent phytocompounds revealing plausible drug candidates. Results In the study, most implied deregulated genes were MRP gene family, ICT1, NDUFA12, VDAC3, APOO, TOMM5, COX6C, COX7B, EDN1 and EDN3 genes whose functional enrichment suggests flawed metabolism of proteins and damaged mitochondrial translation. With high binding affinity, less toxicity at higher dose level Lupeol, Beta-Amyrin, Beta-Elemene, Stigmasterol, Gymnestrogenin and Dammarane proves to be efficient drug candidates. Conclusion The findings of this study imply better understanding of the molecular mechanism of the disorder and encourage further clinical studies pertaining to medicinal natural phytocompounds of Gymnema sylvestre.

Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. Methodology: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. Results: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. Conclusion: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.

The cotton mealybug, Phenacoccus solenopsis Tinsley and papaya mealybug, Paracoccus marginatus Williams and Granara de Willink (Hemiptera: Pseudococcidae) are becoming major threats to the production of Gymnema sylvestre R. Br. (Asclepiadaceae) in India. Management mainly depends on chemical insecticides which cause a serious problem of pesticide residue and insecticide resistance. The use of biorational insecticides such as biopesticides, botanicals, insect growth regulators, and microbial insecticides is important components of an Integrated Pest Management (IPM) program for successful management. We evaluated the bio-efficacy of twelve biorational insecticides, including entomopathogenic fungi (EPF), using the leaf spray method in laboratory conditions at 25 ± 1 °C, 70 % ± 5 % RH. The results revealed that the highest percent mortality was recorded by acetamiprid 20 % SP (100.00 %), followed by azadirachtin (98.27 %), Lecanicillium muscarium (2 × 109 spores/mL) (85.70 %) and Ocimum sanctum leaf extract (76.87 %) at 120 h after treatment (HAT) in P. solenopsis. In P. marginatus, 100.00 %, 96.39 % and 85.67 % and 74.90 % mortalities were achieved by acetamiprid 20 % SP, azadirachtin, L. muscarium (2 × 109 spores/mL) and O. sanctum leaf extract, respectively, at 120 HAT during the first spray. Various biorational insecticides showed a more or less similar trend of percent mortality in both species during the second spray. In both species, the lowest percent mortality was recorded by Andrographis paniculata leaf extract (46.29, 44.54) and (41.03, 46.39) at 120 Hours after treatment in the first and second spray, respectively. It was concluded that all the prescribed treatments are more effective than the control. Overall, azadirachtin recorded the highest percent mortality after acetamiprid and had the shortest LT50 (12.52 h) and (13.87 h) values in P. solenopsis and P. marginatus, respectively. Our study emphasizes that biopesticides like Azadirachtin 1 % EC (10000 ppm), L. muscarium (2 × 109 spores/mL) (5 mL/L) and O. sanctum leaf extract (5 %) may be recommended as alternatives to synthetic insecticides. Botanicals and EPF would be the most effective approach for sustainable integrated management of P. solenopsis and P. marginatus in the G. sylvestre ecosystem.

Tuberculosis (TB), an infectious disease caused by multi-drug resistant Mycobacterium tuberculosis (Mtb), has been a global health concern. Mtb affects over a third of the world’s population, causing two million deaths annually due to its dormancy and propensity to spread infection during this period. Resuscitation-promoting factor B (RpfB) plays a pivotal role in the growth of Mtb during dormant periods, making it a critical target for eliminating Mtb and curing TB. Gymnema sylvestre is a famous medicinal plant with several medicinal properties, including antimicrobial activity; however, the therapeutic potential of the various reported metabolites of this plant against Mtb has not yet been explored. The aim of this study was to explore the reported natural products of G. sylvestre against the RpfB of the Mtb. A total of 131 reported secondary metabolites of this plant were collected and virtually screened against the RpfB. We particularly targeted the Glu292 residue of RpfB as it is crucial for the catalysis of this protein. From our in-house library, 114 compounds showed a binding affinity higher than the standard drug. The binding stability of the top three lead compounds was further confirmed through MD simulation analysis. Drug likeness analyses indicated that the ten hits had zero violations of the Lipinski rule of five. In addition, analyses of pharmacokinetics, toxicity, and target prediction revealed that the top compounds are devoid of toxicity and do not affect human proteins. Additionally, they reflect multifaceted approach as anti-TB agents. Our selected hits not only exhibit molecular properties favoring physiological compatibility but also exhibit properties enhancing their potential efficacy as therapeutic candidates. The compounds investigated here are worthy of experimental validation for the discovery of novel treatments against TB. Further, this study also provides a promising avenue for research on the pharmacological potential of G. sylvestre.

Variability in chemical composition of Gymnema sylvestre R.Br. (Apocynaceae) sampled from different biogeographical regions of India was investigated. The impact of geographic conditions on gymnemagenin, deacylgymnemic acid, lupeol and stigmasterol content variability was studied by using chromatographic analysis. HPLC analyses showed gymnemagenin and deacylgymnemic acid content to vary between 10.19-23.38 µg/mg and 4.70-35.42 µg/mg (w/w dry weight plant material) respectively, while lupeol and stigmasterol were found to range from 0.57 to 10.8 µg/mg and 0.25 to 15.6 µg/mg (w/w in methanolic extract) respectively, by HPTLC. Taking into account the importance of geographical origin and climatic conditions that significantly affect the production and accumulation of secondary metabolites, the selected accessions/germplasms of G. sylvestre with high concentration of biologically potential phytoconstituents could be useful to industries for harvesting optimum levels of bioactive antidiabetic agent gymnemic acids and other sterols. These elite accessions/germplasms could be promoted and used for mass propagation and cultivation to ensure sustained supply of quality raw material for herbal drug industries, companies and entrepreneurs involved in the profession of medicinal plants and as secondary source of income generation to farmers. [ABSTRACT FROM AUTHOR]

Abstract Background Gymnema sylvestre (Retz.) R. Br. ex Schult. is a well-known medicinal plant against diabetes in India. There is as such no organized cultivation in India, and the plant is still being collected from the wild for their therapeutic uses. It is, therefore, important to estimate the genetic diversity and population genetic structure of G. sylvestre to ascertain the genetically diverse germplasm. The present study, therefore, was undertaken to analyze the genetic variability in 118 accessions belonging to 11 wild populations of G. sylvestre using directed amplification of minisatellite-region DNA (DAMD) and inter simple sequence repeats (ISSR). Results The present genetic analyses of 11 populations with 25 markers (8 DAMD and 17 ISSR) revealed significant genetic diversity (H = 0.26, I = 0.40, PPL = 80.89%) at a species level, while the average genetic diversity at the population level was low. Among the 11 populations studied, PCH and UTK populations showed maximum genetic diversity, followed by KNR and AMB, while TEL population revealed the lowest genetic diversity. AMOVA and G st values (0.18) revealed that most of the genetic variations are found within populations and very less among populations, and higher gene flow (N m = 2.29) was found to be responsible for the genetic homogenization of the populations. The clustering pattern resulting from the UPGMA dendrogram was in congruence with STRUCTURE and PCoA, segregating all the 11 populations into two main genetic clusters: cluster I (populations of North and Central India) and cluster II (populations of South India). The clustering patterns obtained from all three statistical methods indicate that the genetic structure in G. sylvestre populations corresponds to the geographical diversity of the populations and represents a strong genetic structure. Conclusion The genetically diverse populations identified during the present study could be a potential genetic resource for further prospecting and conserving this important plant resource.

The main objective of this research was to perform Gymnema sylvestre (Asclepiadaceae) extract’s phytochemical screening and identify its therapeutic potential. Using a Soxhlet apparatus, the powdered plant material was extracted using ethyl acetate. The preliminary phytochemical analysis confirmed the presence of alkaloids, flavonoids, phenols, glycosides, and steroids. Gas chromatography–mass spectroscopy analysis of the extract was performed and confirmed the presence of 11 compounds. As per the quantitative analysis, the extract exhibited a phenolic content of 948 µg gallic acid equivalent/g dry weight, a total flavonoid content of 398 µg quercetin equivalent/g dry weight, and an alkaloid content of 487 µg atropine equivalent/g dry weight. As per the in vitro cytotoxicity test using A549 cells, the IC50 (half-maximal inhibitory concentration) value for the extract was found to be 76.06 ± 1.26 µg/mL, indicating its cytotoxic effect on the cells. The ethyl acetate extract showed significant antibacterial efficacy, as evidenced by a zone of clearance measuring 3 mm against Escherichia coli and 6 mm against Bacillus subtilis. For anthelmintic activity, the earthworm paralysis time induced by G. sylvestre extract (10 mg/mL) was 28.13 ± 0.8 min, and the time of death was 68.21 ± 1.72 min. In comparison, the reference drug, piperazine citrate (10 mg/mL), caused paralysis in 22.18 ± 1.02 min and resulted in death at 66.22 ± 2.35 min. Similarly, the coagulation time was notably prolonged, with blood clot formation observed at 1 min and 40 s, at a concentration of 1 mg/mL, which underscores the potential anticoagulant or hemostatic modulation properties of G. sylvestre extract. The test extract showed good inhibition of alpha-amylase activity and exhibited an IC50 value of 15.59 µg/mL. The IC50 value for DPPH (2,2-diphenyl-1-picrylhydrazyl)-scavenging activity for the extract was 19.19 µg/mL. Based on the GCMS results, the compound 2,7-dimethyl-undecane was selected for its anticancer potential. Docking studies were conducted with the epidermal growth factor receptor (EGFR) protein, specifically the 5WB7 variant associated with lung cancer. The docking score was −4.5, indicating a potential interaction. Key interaction residues such as ASN328, VAL350, and THR358 were identified. Overall, this research provides valuable insights into the phytochemical composition and diverse biological activities of G. sylvestre extract, offering a foundation for further exploration of its medicinal and pharmacological potential.

The taste of food plays a crucial role in determining what and how much we eat. Thus, interventions that temporarily block sweet taste receptors offer a promising approach to addressing unhealthy behaviours associated with sugary foods. However, the relationship between reduced sweet taste response and food consumption remains unclear, with contradictory findings. Certain studies suggest that a diminished perception of sweetness leads to a sense of fullness and results in reduced food intake, while others suggest the opposite effect. To shed some light, our systematic review looked into the relationship between diminished sweet taste response and food consumption by examining the effects of bioactive compounds that experimentally inhibit sweetness in healthy individuals. This review was registered in the International Prospective Register of Systematic Reviews and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Scottish Intercollegiate Guidelines Network, and covered original papers included in Web of Science, PubMed, Scopus, Food Science Source and Food Science and technology abstracts. We identified 33 peer-reviewed English-language studies that fit the topic and met the inclusion criteria. The current literature predominantly focuses on the immediate impact of oral gymnemic acids, failing to provide preliminary evidence in support of the specific threshold hypothesis, above which food consumption decreases and below which the opposite effect occurs. Additionally, there was inconsistency in the findings regarding the short-term desire to eat following sweetness inhibition. Considering the downstream effects on energy intake and their clinical applications, further research is needed to clarify both the acute within-session effects (i.e., not wanting any more now) and the longer-term effects (i.e., deciding not to start eating) linked to oral sweet-taste-suppressing compounds.

This article, the second in a two-part series, continues the discussion on the nature of the relationship between the level of sweet taste suppression and eating behaviour, but in animal rather human subjects. In particular, the aim was to review the scientific literature on the impact that bioactive compounds that decrease oral sweet sensations have on intake, preference and physiological status in preclinical studies. This review was registered in the International Prospective Register of Systematic Reviews and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Scottish Intercollegiate Guidelines Network and covered original papers included in Web of Science, PubMed, Scopus, Food Science Source and Food Science and technology abstracts. We identified 28 peer-reviewed English-language studies that fit the topic and met the inclusion criteria. We identified three plant species, Gymnema sylvestre, Hovenia dulcis, and Ziziphus jujuba, that possess acute sweetness-inhibitory properties. When administered orally, these plants reduced neural responses to sweet stimuli and decreased consumption. However, studies on the longer-term effects of antisweet activity remain to be conducted. Translating the valuable insights into the mechanisms underlying the relationship between sweet taste impairment and eating behaviour into practical clinical applications are discussed.

Excessive consumption of added sugars is linked to chronic diseases, such as obesity, diabetes, dyslipidaemia or cardiovascular disease; and public health is searching for new strategies to reduce it. Although plant-derived bioactive compounds with inhibitory properties of sweet taste like Gymnema sylvestre show the potential to reduce sugar intake acutely, their impact after repeated administration is unknown. Therefore, we examined the changes of single and repeated exposures of a Gymnema sylvestre constituent, gurmarin, in sweet beverage consumption and preference in a preclinical model. 24 Wistar rats (50 % females) were divided into experimental (gurmarin) and two control groups (gymnemic acids or phosphate buffer solutions) according to the substances orally applied. Then acceptance and preference tests with sugar were performed within (Experiment 1) and between sessions (Experiment 2). We found that administering gurmarin decreased sucrose intake significantly, even after multiple treatments, without rebound effects. These findings suggest that sweet taste suppressors could be an effective tool for reducing long-term sugar consumption when repeatedly administrated.

The primary control of dysmetabolic patients is extremely challenging worldwide, with inadequate dietary habits and sporadic physical activity among the key risk factors for metabolic syndrome onset. Nowadays, there is no exclusive treatment for this condition, and considering that preventive measures usually fail, new therapeutic approaches need to be proposed and investigated. This present pilot study compared the effects of diet alone and in association with a combination of myo-inositol and d-chiro-inositol in their 40:1 ratio, α-lactalbumin, and Gymnema sylvestre on different metabolic parameters in obese dysmetabolic patients. To this purpose, 37 patients with BMI between 30 and 40 and fasting blood glucose between 100 and 125 mg/dL were divided into two groups: (i) the control group followed a hypocaloric Mediterranean diet, (ii) while the study group was also supplemented with a daily dosage of two sachets, each one containing 1950 mg myo-inositol, 50 mg d-chiro-inositol, 50 mg α-lactalbumin, and 250 mg Gymnema Sylvestre. After a 6-month treatment, all parameters improved in both groups. Nevertheless, the treated group experienced a greater improvement, especially concerning the variation from the baseline of HOMA index, triglycerides, BMI, body weight, and waist circumference. These findings support the supplementation with myo-inositol and d-chiro-inositol in the 40:1 ratio, α-lactalbumin, and Gymnema sylvestre as a therapeutical strategy to potentiate the beneficial effects induced via dietary programs in dysmetabolic patients. [ABSTRACT FROM AUTHOR]

Gymnema sylvestre (Retz.) R.Br. ex Sm. is a perennial climbing shrub found over the tops of woody trees in tropical forest of India. It is a miracle plant having great anti-diabetic potential. The phytoconstituents of Gymnema sylvestre were isolated and their chemistry and structures were studied and elucidated. An inspection of literature revealed some extraordinary pharmacological activities of this plant. The present review is an effort to emphasize the various traditional use as well as, phytochemistry, pharmacological uses therapeutic properties on G. sylvestre. [ABSTRACT FROM AUTHOR]

Gymnema sylvestre is traditionally used as an herbal remedy for diabetes. The effect of Gymnema sylvestre supplementation on beta cell and hepatic activity was explored in an alloxan-induced hyperglycemic adult rat. Animals were made hyperglycemic via a single inj. (i.p) of Alloxan. Gymnema sylvestre was supplemented in diet @250 mg/kg and 500 mg/kg b.w. Animals were sacrificed, and blood and tissues (pancreas and liver) were collected for biochemical, expression, and histological analysis. Gymnema sylvestre significantly reduced blood glucose levels with a subsequent increase in plasma insulin levels in a dosage-dependent manner. Total oxidant status (TOS), malondialdehyde, LDL, VLDL, ALT, AST, triglyceride, total cholesterol, and total protein levels were reduced significantly. Significantly raised paraoxonase, arylesterase, albumin, and HDL levels were also observed in Gymnema sylvestre treated hyperglycemic rats. Increased mRNA expression of Ins-1, Ins-2, Gck, Pdx1, Mafa, and Pax6 was observed, while decreased expression of Cat, Sod1, Nrf2, and NF-kB was observed in the pancreas. However, increased mRNA expression of Gck, Irs1, SREBP1c, and Foxk1 and decreased expression of Irs2, ChREBP, Foxo1, and FoxA2 were observed in the liver. The current study indicates the potent effect of Gymnema sylvestre on the transcription modulation of the insulin gene in the alloxan-induced hyperglycemic rat model. Enhanced plasma insulin levels further help to improve hyperglycemia-induced dyslipidemia through transcriptional modulation of hepatocytes. [ABSTRACT FROM AUTHOR]

The invention of an easy synthetic approach for extremely impactful nanomaterials (NMs) is one of the crucial research areas in modern science and engineering. In the present work, we describe a cost-effective, simple, rapid and environmentally gracious biogenic fabrication of nickel/nickel oxide nanoparticles (Ni/NiO NPs) using Gymnema sylvestre as a natural fuel. The textural characteristics of as-prepared Ni/NiO NPs were explored using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), diffuse reflectance spectra (DRS), photoluminescence spectroscopy (PL), fieldemission scanning electron microscope (FESEM), energy dispersive X-ray analysis (EDX), and highresolution transmission electron microscopy (HRTEM). XRD affirmed the crystalline nature and phase formation of Ni/NiO NPs. The FTIR spectrum ascertains the formation of Ni/NiO NPs, and the band gap of 4.29 eV is revealed from DRS studies. Ni/NiO NPs display an intense emission peak at 576.2 nm in their PL spectrum. The fabrication of pseudo-spherical Ni/NiO NPs was displayed by FESEM and HRTEM images. The particle size obtained from HRTEM was 21 nm, which resembles the median crystallite size ascertained from the XRD data. Additionally, the plausible mechanism for Ni/NiO NPs formation is illustrated. Moreover, as-synthesized Ni/NiO NPs displayed considerable antifungal potential against Candida albicans and Aspergillus niger. Results revealed that the Gymnema sylvestre leaves extract can synthesize Ni/NiO NPs with appealing biological effectiveness for application in the nanomedicine sector. [ABSTRACT FROM AUTHOR]

Gymnema sylvestre (GS) is a perennial woody vine native to tropical Asia, China, the Arabian Peninsula, Africa and Australia. GS has been used as a medicinal plant with potential anti-microbial, anti-inflammatory and anti-oxidant properties. This study was conceptualized to evaluate the cytotoxicity potential of Gymnema sylvestre saponin rich fraction (GSSRF) on breast cancer cell lines (MCF-7 and MDA-MB-468) by SRB assay. The anti-tumor activity of GSSRF was assessed in tumor-bearing Elrich ascites carcinoma (EAC) and Dalton's lymphoma ascites (DLA) mouse models. The anti-oxidant potential of GSSRF was assessed by DPPH radical scavenging assay. The acute toxicity of GSSRF was carried out according to OECD guideline 425. The yield of GSSRF was around 1.4% and the presence of saponin content in GSSRF was confirmed by qualitative and Fourier transform infrared spectroscopic (FTIR) analysis. The in vitro cytotoxic effects of GSSRF on breast cancer cell lines were promising and found to be dose-dependent. An acute toxicity study of GSSRF was found to be safe at 2000 mg/kg body weight. GSSRF treatment has shown a significant increase in the body weight and the life span of EAC-bearing mice in a dose-dependent manner when compared with the control group. In the solid tumor model, the doses of 100 and 200 mg/kg body weight per day have shown about 46.70% and 60.80% reduction in tumor weight and controlled the tumor weight until the 30th day when compared with the control group. The activity of GSSRF in both models was similar to the cisplatin, a standard anticancer agent used in the study. Together, these results open the door for detailed investigations of anti-tumor potentials of GSSRF in specific tumor models, mechanistic studies and clinical trials leading to promising novel therapeutics for cancer therapy. [ABSTRACT FROM AUTHOR]

This study investigated the chemical constituents, antioxidant potential, and in vitro and in silico antidiabetic activity of Gymnema sylvestre. Column chromatography and spectroscopic techniques identified twelve compounds from the methanol extract, including 4 sterols (1 – 4), 5 triterpenoids (5 – 9), and 3 flavonoids (10 – 12). The chemophenetic significance of all compounds was also investigated. The antioxidant capacity of the extract and compounds (1 – 4) was evaluated using FRAP and DPPH assays. The extract exhibited strong free radical scavenging activity (IC 50 = 48.34 µg/mL), while compounds (1 – 4) displayed varying degrees of efficacy (IC 50 = 98.30–286.13 µg/mL). The FRAP assay indicated significant reducing power for both extract and compounds (58.54, 47.61, 56.61, and 49.11 mg Eq.VitC/g for extract and compounds 1 & 2 , 3 , and 4 , respectively). The antidiabetic potential was assessed through α -amylase and α -glucosidase enzyme inhibition assays. The crude extract demonstrated the most potent inhibition (IC 50 = 218.46 and 57.42 µg/mL for α -glucosidase and α -amylase respectively) suggesting its potential for managing postprandial hyperglycaemia. In silico studies employed molecular docking and dynamics simulations to elucidate the interactions between identified compounds and α -amylase/ α -glucosidase enzymes. The results revealed promising binding affinities between the compounds and target enzymes, with compound 6 demonstrating the highest predicted inhibitory activity with −10 kcal/mol and −9.1 kcal/mol for α -amylase and α -glucosidase, respectively. This study highlights the presence of diverse bioactive compounds in Gymnema sylvestre. The extract exhibits antioxidant properties and inhibits carbohydrate-digesting enzymes, suggesting its potential as a complementary therapeutic approach for managing hyperglycaemia associated with type 2 diabetes. [Display omitted] • Gymnema sylvestre extract contains sterols, triterpenoids, and flavonoids. • The extract exhibits strong free radical scavenging and reducing power, indicating antioxidant potential. • The extract inhibits α-amylase and α-glucosidase enzymes, suggesting potential for managing postprandial hyperglycaemia. • In silico study predicts binding affinity between identified compounds and target enzymes, supporting antidiabetic activity. • Gymnema sylvestre extract warrants further investigation as a complementary therapy for type 2 diabetes. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is one of the most common cancers. It accounts for 90-96% incidence of all head and neck cancers. Understanding molecular pathogenesis can pave the way for precision-based treatment as well as improve the quality of life. The aim of the present study was to investigate the effects of Gymnema sylvestre (GS) and Ethylenediaminetetraacetic acid (EDTA) on ctDNA yield in OSCC. The prospective study was conducted on 20 primary OSCC patients. The blood samples for patients taken and was preserved in tubes containing GS and EDTA. Polymerase chain reaction (PCR) was carried out to quantify the ctDNA. EDTA and GS have almost similar effects and similar yields on ctDNA from the blood of OSCC. It was concluded that apart from chemical anticoagulants like EDTA, GS can also be used as in-vitro laboratory anticoagulants for storing blood from OSCC, which can be used for molecular analysis. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (Sa) is an opportunistic pathogen capable of causing various infections ranging from superficial skin infections to life-threatening severe diseases including pneumonia and sepsis. Sa produces biofilms readily on biotic and abiotic surfaces. Biofilm cells are embedded in a protective polysaccharide matrix and show an innate resistance to antibiotics, disinfectants, and clearance by host defenses. Additionally, biofilms serve as a source for systemic dissemination. Moreover, infections associated with biofilms may result in longer hospitalizations, a need for surgery, and may even result in death. Agents that inhibit the formation of biofilms and virulence without affecting bacterial growth to avoid the development of drug resistance could be useful for therapeutic purposes. In this regard, we identified and purified a small cyclic peptide, gurmarin, from a plant source that inhibited the formation of Sa biofilm under in vitro growth conditions without affecting the viability of the bacterium. The purified peptide showed a predicted molecular size of ~4.2 kDa on SDS-PAGE. Transcriptomic analysis of Sa biofilm treated with peptide showed 161 differentially affected genes at a 2-fold change, and some of them include upregulation of genes involved in oxidoreductases and downregulation of genes involved in transferases and hydrolases. To determine the inhibitory effect of the peptide against Sa biofilm formation and virulence in vivo, we used a rat-implant biofilm model. Sa infected implants with or without peptide were placed under the neck skin of rats for seven days. Implants treated with peptide showed a reduction of CFU and lack of edema and sepsis when compared to that of control animals without peptide. Taken together, gurmarin peptide blocks Sa biofilm formation in vitro and in vivo and can be further developed for therapeutic use.

Background and aims: Gymnema sylvestre, commonly known as periploca of the woods, belongs to the family Asclepiadaceae. Several studies have reported that the plant possesses some medicinal properties. A wide variety of diseases such as cancer, diabetes, and cardiovascular disease in human are directly associated with oxidative stress. This study was aimed to examine the possible antioxidant activity of ethyl acetate and aqueous fractions of G. sylvestre.Methods: The antioxidant property of the extract fractions was determined using in vitro assays, 2,2 - diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant potential (FRAP) methods. To identify compounds in the fractions with the antioxidant property, liquid chromatography-mass Spectroscopy (LC-MS) was carried out.Results: Ethyl acetate fraction showed the highest DPPH scavenging activity (significantly higher than the standard) [(88.98±2.69)% with lowest IC50 at 1.01±0.04 mg/cm3] compared to aqueous fraction [(83.86±0.64)% with highest IC50 at 1.04±0.01 mg/cm3] and standard ascorbic acid [(84.71±0.60)% and IC50 1.03±0.01 mg/cm3]. However the aqueous fraction was significantly weaker than the standard for DPPH scavenging activity. The FRAP assay yielded similar result to those of DPPH assay [(0.452±0.002)%, (0.426±0.000)%, and (0.425±0.001)% for ethyl acetate extract, aqueous extract and the standard (ascorbic acid), respectively]. LC-MS of the fractions revealed different compounds including C17H15O7, C27H20O18, C28H24O16 (in ethyl acetate extract) and C15H10O9S, C15H16O12, C27H26O16 (in aqueous extract). Molecular docking analysis of the identified compounds against some useful enzymes (alpha glucosidase and alpha amylase) suggested that these compounds could be a potential inhibitors of the enzymes.Conclusion: Therefore, G. sylvestre leaf extract could be recommended as a potential natural antioxidant source that could be used in preventing oxidative stress-associated diseases and in drug management.

Abstract 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 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.

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.

Gymnema sylvestre is traditionally used as an herbal remedy for diabetes. The effect of Gymnema sylvestre supplementation on beta cell and hepatic activity was explored in an alloxan-induced hyperglycemic adult rat. Animals were made hyperglycemic via a single inj. (i.p) of Alloxan. Gymnema sylvestre was supplemented in diet @250 mg/kg and 500 mg/kg b.w. Animals were sacrificed, and blood and tissues (pancreas and liver) were collected for biochemical, expression, and histological analysis. Gymnema sylvestre significantly reduced blood glucose levels with a subsequent increase in plasma insulin levels in a dosage-dependent manner. Total oxidant status (TOS), malondialdehyde, LDL, VLDL, ALT, AST, triglyceride, total cholesterol, and total protein levels were reduced significantly. Significantly raised paraoxonase, arylesterase, albumin, and HDL levels were also observed in Gymnema sylvestre treated hyperglycemic rats. Increased mRNA expression of Ins-1, Ins-2, Gck, Pdx1, Mafa, and Pax6 was observed, while decreased expression of Cat, Sod1, Nrf2, and NF-kB was observed in the pancreas. However, increased mRNA expression of Gck, Irs1, SREBP1c, and Foxk1 and decreased expression of Irs2, ChREBP, Foxo1, and FoxA2 were observed in the liver. The current study indicates the potent effect of Gymnema sylvestre on the transcription modulation of the insulin gene in the alloxan-induced hyperglycemic rat model. Enhanced plasma insulin levels further help to improve hyperglycemia-induced dyslipidemia through transcriptional modulation of hepatocytes.

The invention of an easy synthetic approach for extremely impactful nanomaterials (NMs) is one of the crucial research areas in modern science and engineering. In the present work, we describe a cost-effective, simple, rapid and environmentally gracious biogenic fabrication of nickel/nickel oxide nanoparticles (Ni/NiO NPs) using Gymnema sylvestre as a natural fuel. The textural characteristics of as-prepared Ni/NiO NPs were explored using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), diffuse reflectance spectra (DRS), photoluminescence spectroscopy (PL), field-emission scanning electron microscope (FESEM), energy dispersive X-ray analysis (EDX), and high-resolution transmission electron microscopy (HRTEM). XRD affirmed the crystalline nature and phase formation of Ni/NiO NPs. The FTIR spectrum ascertains the formation of Ni/NiO NPs, and the band gap of 4.29 eV is revealed from DRS studies. Ni/NiO NPs display an intense emission peak at 576.2 nm in their PL spectrum. The fabrication of pseudo-spherical Ni/NiO NPs was displayed by FESEM and HRTEM images. The particle size obtained from HRTEM was 21 nm, which resembles the median crystallite size ascertained from the XRD data. Additionally, the plausible mechanism for Ni/NiO NPs formation is illustrated. Moreover, as-synthesized Ni/NiO NPs displayed considerable antifungal potential against Candida albicans and Aspergillus niger. Results revealed that the Gymnema sylvestre leaves extract can synthesize Ni/NiO NPs with appealing biological effectiveness for application in the nanomedicine sector.

Abstract Background Squalene synthase (SQS) is a rate-limiting enzyme necessary to produce pentacyclic triterpenes in plants. It is an important enzyme producing squalene molecules required to run steroidal and triterpenoid biosynthesis pathways working in competitive inhibition mode. Reports are available on information pertaining to SQS gene in several plants, but detailed information on SQS gene in Gymnema sylvestre R. Br. is not available. G. sylvestre is a priceless rare vine of central eco-region known for its medicinally important triterpenoids. Our work aims to characterize the GS-SQS gene in this high-value medicinal plant. Results Coding DNA sequences (CDS) with 1245 bp length representing GS-SQS gene predicted from transcriptome data in G. sylvestre was used for further characterization. The SWISS protein structure modeled for the GS-SQS amino acid sequence data had MolProbity Score of 1.44 and the Clash Score 3.86. The quality estimates and statistical score of Ramachandran plots analysis indicated that the homology model was reliable. For full-length amplification of the gene, primers designed from flanking regions of CDS encoding GS-SQS were used to get amplification against genomic DNA as template which resulted in approximately 6.2-kb sized single-band product. The sequencing of this product through NGS was carried out generating 2.32 Gb data and 3347 number of scaffolds with N50 value of 457 bp. These scaffolds were compared to identify similarity with other SQS genes as well as the GS-SQSs of the transcriptome. Scaffold_3347 representing the GS-SQS gene harbored two introns of 101 and 164 bp size. Both these intronic regions were validated by primers designed from adjoining outside regions of the introns on the scaffold representing GS-SQS gene. The amplification took place when the template was genomic DNA and failed when the template was cDNA confirmed the presence of two introns in GS-SQS gene in Gymnema sylvestre R. Br. Conclusion This study shows GS-SQS gene was very closely related to Coffea arabica and Gardenia jasminoides and this gene harbored two introns of 101 and 164 bp size.

Objective: To investigate the combined therapeutic potential of Gymnema (G.) sylvestre and Pergularia (P.) daemia on letrozole-induced polycystic ovarian syndrome (PCOS) in rats. Methods: Thirty six healthy female Wistar rats with regular estrus cycles were randomly divided into six groups each of 6. Group I received 1 mL of 0.5% carboxyl methyl cellulose orally and served as the vehicle control group, while groups II to VI were treated with letrozole (1 mg/kg body weight p. o.) for 21 days to induce PCOS. After induction of PCOS, group II served as the PCOS control group, without treatment; group III received metformin (20 mg/kg body weight p. o.) as the standard group, and groups IV to VI received G. sylvestre (100 mg/kg body weight p. o.), P. daemia (300 mg/kg body weight p. o.), and the combination of G. sylvestre and P. daemia, respectively, for 28 days. Vaginal smears were collected from all rats daily throughout the study to determine the phases of the estrus cycle. After completing the treatment schedule, oral glucose tolerance test, serum lipid profile and reproductive hormonal analysis were carried out. Subsequently, the rats were sacrificed to collect ovary and uterus for histopathological examination. Results: The PCOS control rats showed a significant irregularity in the estrus cycle, hyperglycemia, and the altered serum lipid profile such as the increased low and very low density lipoprotein, triglyceride, and decreased high density lipoproteins. In addition, the PCOS control rats showed a significant increase in serum luteinizing hormone, testosterone, and estrogen, and decrease in follicle stimulating hormone and progesterone. These changes were significantly revoked in all the treatment groups. The test drugs also significantly reduced the gained ovary weight (P

Gymnema sylvestre (GS) is a perennial woody vine native to tropical Asia, China, the Arabian Peninsula, Africa and Australia. GS has been used as a medicinal plant with potential anti-microbial, anti-inflammatory and anti-oxidant properties. This study was conceptualized to evaluate the cytotoxicity potential of Gymnema sylvestre saponin rich fraction (GSSRF) on breast cancer cell lines (MCF-7 and MDA-MB-468) by SRB assay. The anti-tumor activity of GSSRF was assessed in tumor-bearing Elrich ascites carcinoma (EAC) and Dalton’s lymphoma ascites (DLA) mouse models. The anti-oxidant potential of GSSRF was assessed by DPPH radical scavenging assay. The acute toxicity of GSSRF was carried out according to OECD guideline 425. The yield of GSSRF was around 1.4% and the presence of saponin content in GSSRF was confirmed by qualitative and Fourier transform infrared spectroscopic (FTIR) analysis. The in vitro cytotoxic effects of GSSRF on breast cancer cell lines were promising and found to be dose-dependent. An acute toxicity study of GSSRF was found to be safe at 2000 mg/kg body weight. GSSRF treatment has shown a significant increase in the body weight and the life span of EAC-bearing mice in a dose-dependent manner when compared with the control group. In the solid tumor model, the doses of 100 and 200 mg/kg body weight per day have shown about 46.70% and 60.80% reduction in tumor weight and controlled the tumor weight until the 30th day when compared with the control group. The activity of GSSRF in both models was similar to the cisplatin, a standard anticancer agent used in the study. Together, these results open the door for detailed investigations of anti-tumor potentials of GSSRF in specific tumor models, mechanistic studies and clinical trials leading to promising novel therapeutics for cancer therapy.

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.

A study on 81 individuals (18-75 years old) with mildly impaired fasting blood glucose (FBG) concentrations (98-125 mg/dL) was undertaken to investigate the tolerability of a food supplement (FS) based on Zea mays and Gymnema sylvestre extracts, zinc, and chromium and its efficacy on glucose and lipid metabolism. The subjects were randomized into three groups (27 in each group) and supplemented with one or two tablet(s)/day of FS (groups 1 and 2, respectively), or two tablets/day of placebo (group 3). Blood sampling was carried out at baseline (t0) and after a 3-month treatment (t1), and biochemical parameters associated with glucose and lipid metabolism and kidney and liver toxicity were evaluated. Compared to the placebo, FBG and glycated haemoglobin (HbA1c) were significantly ( p < 0.001) reduced in group 1 subjects. In contrast, at the doses of one and two tablet(s)/day, the FS exerted no effect on the other parameters examined. We conclude that in subjects with slightly impaired FBG, ingestion of a FS based on Z. mays and G. sylvestre extracts, zinc, and chromium over 3 months lowers FBG and modulates glucose homeostasis by improving glucose metabolism. These beneficial effects occur in the absence of biochemical evidence of kidney and liver toxicity.

Two new pregnane glycosides were isolated from the leaves of Gymnema sylvestre (Retz.) R.Br. ex Sm. Their chemical structures were determined as (20S)−12β-tigloyloxy-5α-hydroperoxy-3β,8β,14β,17β,20-pentahydroxypregn-6-ene 3-O-β-D-glucopyranosyl-(1→4)‐6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (1) and (20S)−12β-benzoyloxy-5α-hydroperoxy-3β,8β,14β,17β,20-pentahydroxypregn-6-ene 3-O-β-D-glucopyranosyl-(1→4)‐6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (2) on the basis of the extensive spectroscopic methods, including 1D, 2D NMR, HRESIMS, and in comparison with the reported data. At the concentration of 200 µM, compounds 1 and 2 showed moderate anti α-glucosidase and α-amylase activities with inhibitory percentage of 31.1 ± 1.2 and 42.3 ± 1.7% (for α-glucosidase), and 27.8 ± 1.3 and 34.5 ± 1.5% (for α-amylase), respectively. [ABSTRACT FROM AUTHOR]

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 < 0.05) the levels of biochemical indices including the aspartate transaminases, alanine transaminase, alkaline phosphates, bilirubin, proteins, urea, creatinine, and white blood cells (WBC) counts when compared with the non-treated control. However, the extract and fractions at 100 mg/kg BW did not cause any significant (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. [ABSTRACT FROM AUTHOR]

Gymnema sylvestre R.Br. is famous medicinal plant among diabetics for its gymnemic acid content. It also contains flavonoids, which are an essential component in various other products. Though some molecular information on the biosynthesis of gymnemic acid, polyoxypregnane, micro RNAs and photosynthetic efficiency is available, there is no gene level information available on the biosynthesis of flavonoids in this plant. RNA was extracted from winter-collected Gymnema sylvestre leaves and cDNA libraries were prepared and used for next generation sequencing. De novo transcriptome assembly were prepared and Coding DNA Sequences (CDS) of 13 major genes involved in flavonoids biosynthesis were identified from transcriptome data. Phenylalanine ammonia lyase gene containing full-length CDS was employed for in silico protein modelling and subsequent quality assessment. These models were then compared against publicly available databases. To confirm the identification of these genes, a similarity search was conducted using the NCBI BLAST tool. Therefore, in the present study, an effort has been made to provide molecular insights into flavonoid biosynthesis pathway by examining the expressed transcripts in G.sylvestre. Gene sequences of total thirteen major genes viz., phenylalanine ammonia lyase, 4-coumarate CoA ligase, cinnamic acid 4-hydroxylase, shikimate O-hydroxycinnamoyl transferase, coumaroyl quinate (coumaroyl shikimate) 3′-monooxygenase, caffeoyl-CoA O-methyltransferase, chalcone synthase, chalcone isomerase, naringenin 3-dioxygenase, flavanol synthase, flavonoid 3′-monooxygenase, Flavanone 7-O-glucoside 2″-O-beta-L-rhyamnosyltransferase and leucoanthocyanidin dioxygenase were identified and a putative pathway of flavonoids biosynthesis has been illustrated based on transcriptome data. This transcriptome study has contributed gene-level insights into the biosynthesis of flavonoids in plants as a whole and represents the first report within a non-model plant, Gymnema sylvestre perticullarly. [ABSTRACT FROM AUTHOR]

Abstract Background Gymnema sylvestre is a medicinal woody perennial vine known for its sweetening properties and anti-diabetic therapeutic uses in the modern and traditional medicines. Its over-exploitation for the therapeutic uses and to meet the demand of pharmaceutical industry in raw materials supply for the production of anti-diabetic drugs has led to considerable decline in its natural population. Results An efficient system of shoot bud sprouting from nodal segment explants and indirect plant regeneration from apical meristem-induced callus cultures of G. sylvestre have been developed on Murashige and Skoog (MS) medium amended with concentrations of cytokinins. Of the three growth regulators tested, N 6-benzylaminopurine (BAP) was the most efficient and 2.0 mg L−1 gave the best shoot formation efficiency. This was followed by thidiazuron (TDZ) and kinetin (Kin) but, most of the TDZ-induced micro shoots showed stunted growth. Multiple shoot formation was observed on medium amended with BAP or TDZ at higher concentrations. The produced micro shoots were rooted on half strength MS medium amended with auxins and rooted plantlets acclimatized with 87% survival of the regenerates. Conclusions The developed regeneration system can be exploited for genetic transformation studies, particularly when aimed at producing its high yielding cell lines for the anti-diabetic phytochemicals. It also offers opportunities for exploring the expression of totipotency in the anti-diabetic perennial vine.

Gymnema sylvestre, a plant typical of India, has long been known for its hypoglycemic effects. The objective of this study was to evaluate the effect of G. sylvestre administration on glycemic control, insulin secretion, and insulin sensitivity in patients with impaired glucose tolerance (IGT). A randomized, double-blind, placebo-controlled clinical trial was conducted in 30 patients with IGT. Fifteen patients randomly received G. sylvestre in doses of 300 mg b.i.d. and the other 15 received placebo in the same way. Before and after the intervention, anthropometric and metabolic measurements were taken, including 2-h oral glucose tolerance test (2-h OGTT), fasting plasma glucose, glycated hemoglobin A1c (A1C), and the lipid profile panel. Areas under the curve of glucose and insulin were calculated, as well as the insulinogenic, Stumvoll, and Matsuda indices. Wilcoxon, Mann–Whitney U, and chi-square or Fisher's exact tests were performed, and a P-value ≤.05 was considered statistically significant. There was a significant reduction in 2-h OGTT (9.1 ± 1.2 vs. 7.8 ± 1.7 mmol/L, P = .003), A1C (5.8 ± 0.3% vs. 5.4 ± 0.4%, P = .025), body weight, body mass index, and low-density lipoprotein cholesterol levels in the G. sylvestre group, with an increment in the Matsuda index (1.8 ± 0.8 vs. 2.4 ± 1.2, P = .008). At the end of the intervention, 46.7% of the patients obtained normal values in A1C. In conclusion, G. sylvestre administration in patients with IGT decreased 2-h OGTT and A1C, increasing insulin sensitivity. There were also improvements in anthropometric measures and the lipid profile. [ABSTRACT FROM AUTHOR]

The objective of the current research was to validate the hepatoprotective and anti-hyperlipidemic activities of C. bonduc seed kernels (CBSK) and G. sylvestre leaves (GSL) hydro-methanolic extracts, separately and in combination (CBSKE+GSLE) in alloxan-induced diabetic rat model for 28 days. Diabetes was induced by i.p. injection of alloxan monohydrate (140 mg/kg body weight) to albino Wistar rats. Six groups of rats (n=9) were used. Group 1 was the normal control; group 2 was diabetic control. After induction of diabetes metformin (150mg/kg), CBSKE (400mg/kg), GSLE (400 mg/kg) and CBSKE+GSLE (400mg/kg) were administered to diabetic rat groups 3, 4, 5 and 6 respectively for a period of 28 days. Diabetic rats exhibited an increase in serum blood glucose, liver function markers and lipid profile. Treatment of diabetic rats with metformin, CBSKE, GSLE and CBSKE+GSLE for 4 weeks significantly produced hepatoprotective and hypolipidemic effect via amelioration of raised serum glucose, liver profile, and lipid profile. The outcomes of this study suggest that G. sylvestre leaves and C. bonduc seed kernels have hepatoprotective and hypolipidemic potential which possibly help in managing diabetes-induced liver injury and hyperlipidemia. [ABSTRACT FROM AUTHOR]