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Gymnema sylvestre, commonly known as Gurmar and belonging to the family Asclepiadaceae, is widely distributed in India, Malaysia, Sri Lanka, Australia, Indonesia, Japan, Vietnam, tropical Africa, and the southwestern region of the Republic of China. The plant G. sylvestre is traditionally used as a sugar destroyer in glycosuria and other urinary diseases. The drug is also used in the composition of Ayurvedic preparations such as Ayaskri, Varunadi kasaya, Varunadighrtam, and Mahakalyanakaghrtam. The present review focuses on the reports available in various literatures. The various chemical constituents isolated include saponins, carbohydrates, anthraquinone derivatives, flavones, flavonoids, formic acid, resins, phytin, etc. The chief constituents are saponins like gymnemic acids, gymnemasaponins, gymnemasides, and gymnemagenin. Gymnema sylvestre is found in capsule, tablet, powder, and tea powder forms. A tablet containing 200-400mg of gymnemic acid is used as a supplement for diabetes and to promote healthy pancreatic function. A 100mg capsule helps maintain blood sugar levels in the normal range and reduce inflammation. Gymnema sylvestre helps to fight sugar cravings and neutralize cravings for sweets. [ABSTRACT FROM AUTHOR]

Bone tissue engineering deals with the design of bone scaffolds. The selection of porous scaffold for osteoblast attachment and suppression of microbial infections are the major challenges that were addressed by designing gelatin scaffolds conjugated with gymnemic acid. Gelatin scaffold was prepared by loading gymnemic acid and morphological characterization, porosity, water absorption behavior, and biocompatibility of the scaffold were studied. The scaffold was introduced to the rat calvarial bone defect (BD) and analyzed the serum C reactive protein, alkaline phosphatase activity, and histology for 1 month to study the reconstruction. Adult Sprague–Dawley rats were used as sham operated control, animal with BD, and animal with BD which was implanted with scaffold (BDMB). The scanning electron micrograph revealed porous nature of scaffold. There was no significant difference in water absorption ability of scaffold. The C reactive protein was not observed in the serum collected on the 5th day postsurgery, supported the biocompatibility. The alkaline phosphatase activity in BDMB was increased when compared with BD on 15th and 20th day and then decreased. New bone tissue formation was detected with hematoxylin–eosin staining. The scaffold is effective in enhancing bone regeneration, which will have therapeutic significance in orthopedics and dentistry. [ABSTRACT FROM AUTHOR]

Background: Nephrotoxicity refers to the toxigenic impact of compounds and medications on kidney function. There are a variety of drug formulations, and some medicines that may affect renal function in multiple ways via nephrotoxins production. Nephrotoxins are substances that are harmful to the kidneys. Purpose: This investigation examines the renoprotective effect of gymnemic acid (GA) on Wistar rats in gentamicin-induced nephrotoxicity by analyzing serum, kidney, and histopathological markers. Study-design/methods: The current study investigated the protective effect of GA at doses of 20, 40, and 60 mg/kg against gentamicin-induced nephrotoxicity in rats. Vitamin E was administered to compare the antioxidant capacity and efficacy of GA. In addition to the treatment groups, 100 mg/kg of gentamicin was administered intraperitoneal for 14 days. At the end of the study protocol, kidney homogenate, blood, and serum were evaluated biochemically. Serum creatinine, blood urea, glomerular filtration rate (GFR), mitochondrial dysfunctions, inflammatory cytokines, and renal oxidative stress were examined to assess gentamicin-induced nephrotoxicity. In addition, the impact of GA on the above-mentioned nephrotoxic markers were evaluated and further confirmed by histological analysis. Results: This study establishes a correlation between antibiotic use, especifically aminoglycosides and acute renal failure. The research demonstrates the nephrotoxic effects of aminoglycosides, inducing mitochondrial ETC-complex dysfunction, and renal tissue inflammation in experimental rats. GA's antioxidant properties restored renal oxidative stress markers, reducing kidney inflammation and injury. Histopathological analysis revealed a significant reduction in renal injury with GA treatment. Additionally, GA demonstrated greater efficacy than Vitamin E in restoring antioxidant potential and mitochondrial enzymes. Conclusion: Consequently, our findings imply that long-term use of GA may be a suitable therapeutic strategy for reducing aminoglycoside toxicity. The current study suggests GA's potential in treating gentamicin-induced nephrotoxicity and acute renal failure, meriting further investigation using advanced techniques. [ABSTRACT FROM AUTHOR]

Diabetes is a chronic disease that affects several organs and can be treated using phytochemicals found in medicinal plants. Gymnema sylvestre (Asclepiadaceae) is one such medicinal plant rich in anti-diabetic properties. The plant is commonly known as madhunashini in Sanskrit because of its ability to cure diabetes (sugar). Gymnemic acid (GA) is a phytochemical (a triterpenoid saponin) responsible for the herb's main pharmacological activity. This secondary metabolite has a lot of potential as a phytochemical with pharmacological properties including nephroprotection, hypoglycemia, antioxidant, antimicrobial, and anti-inflammatory. Gymnema has acquired a lot of popularity in recent years due to its low side effects and high efficacy in healing diabetes, which has led to overexploitation by pharmaceutical enterprises for its biomass in the wild for the purification of gymnemic acid. Modern biotechnological techniques involving the establishment of cell and organ cultures from G. sylvestre will assist us in fulfilling the need for gymnemic acid production. The present review provides insights on the establishment of cell and organ cultures for the production of a potent antidiabetic molecule gymnemic acid. Further, the review also delves into the intricacies of the different strategies for improved production of gymnemic acid using various elicitors. There is huge potential for sustainable production of gymnemic acid which could be met by establishment of bioreactor scale production. Understanding and engineering the biosynthetic pathway could also lead to improved GA production. Key points: • Gymnemic acid is one of the potential anti-diabetic molecules from madhunashini • Cell and organ culture offers potential approach for gymnemic acid production • Elicitation strategies have improved the gymnemic acid production [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]

Acute respiratory distress syndrome (ARDS) is one of the major causes of mortality in COVID-19 patients, due to limited therapeutic options. This prompted us to explore natural sources to mitigate this condition. Gymnema Sylvestre (GS) is an ancient medicinal plant known to have various therapeutic effects. This investigation examined the therapeutic effect of hydroalcoholic extract of Gymnema Sylvestre (HAEGS) against lipopolysaccharide (LPS)-induced lung injury and ARDS in in vitro and in vivo models. UHPLC–HRMS/GC–MS was employed for characterizing the HAEGS and identified several active derivatives including gymnemic acid, gymnemasaponins, gymnemoside, gymnemasin, quercetin, and long fatty acids. Gene expression by RT-qPCR and DCFDA analysis by flow cytometry revealed that several inflammatory cytokine/chemokine, cell injury markers, and reactive oxygen species (ROS) levels were highly upregulated in LPS control and were significantly reduced upon HAEGS treatment. Consistent with the in vitro studies, we found that in LPS-induced ARDS model, pre-treatment with HAEGS significantly suppressed the LPS-induced elevation of inflammatory cell infiltrations, cytokine/chemokine marker expression, ROS levels, and lung injury in a dose-dependent manner. Further mechanistic studies demonstrated that HAEGS suppressed oxidative stress by modulating the NRF2 pathway and ameliorated the ARDS through the NF-κB/MAPK signalling pathway. Additional fractionation results revealed that fraction 6 which has the exclusive composition of gymnemic acid derivatives showed better anti-inflammatory effects (inhibition of IL-6 and IL-1β) at lower concentrations compared to HAEGS. Overall, HAEGS significantly mitigated LPS-induced lung injury and ARDS by targeting the NF-κB/MAPK signalling pathway. Thus, our work unravels the protective role of HAEGS for the first time in managing ARDS. [ABSTRACT FROM AUTHOR]

Gymnema inodorum (Lour.) Decne or Chiang Da, the local northern Thai vegetable, is renowned for its anti-diabetic and hypoglycemic properties and is highly sought after by the functional food industry. This research investigated the relationship between the physiological characteristics, genetic variation, and chemical compositions of different Chiang Da accessions. Two commercial lines (COM1 and COM2) and eight local accessions (BAC1-8) of Chiang Da were gathered and maintained in the same study plot for the investigation of their morphological characteristics, genetic variation, and nutritional and phytochemical constituents. From the morphological data, the two commercial lines were clearly distinctive with their closely related leaf structures. Random amplification of the polymorphic illustrated the genetic diversity between the local accessions and commercial strains in a similar pattern as described by their morphology characteristics and proximate contents. The phytochemical characteristics, nonetheless, projected the two commercial lines in separate groups. The outcome of this study could be beneficial toward the selection of the Chiang Da strains with specific traits for plant breeding programs of functional food interest. [ABSTRACT FROM AUTHOR]

Background: Nephrotoxicity refers to the toxigenic impact of compounds and medications on kidney function. There are a variety of drug formulations, and some medicines that may affect renal function in multiple ways via nephrotoxins production. Nephrotoxins are substances that are harmful to the kidneys.Purpose: This investigation examines the renoprotective effect of gymnemic acid (GA) on Wistar rats in gentamicin-induced nephrotoxicity by analyzing serum, kidney, and histopathological markers.Study-design/methods: The current study investigated the protective effect of GA at doses of 20, 40, and 60 mg/kg against gentamicin-induced nephrotoxicity in rats. Vitamin E was administered to compare the antioxidant capacity and efficacy of GA. In addition to the treatment groups, 100 mg/kg of gentamicin was administered intraperitoneal for 14 days. At the end of the study protocol, kidney homogenate, blood, and serum were evaluated biochemically. Serum creatinine, blood urea, glomerular filtration rate (GFR), mitochondrial dysfunctions, inflammatory cytokines, and renal oxidative stress were examined to assess gentamicin-induced nephrotoxicity. In addition, the impact of GA on the above-mentioned nephrotoxic markers were evaluated and further confirmed by histological analysis.Results: This study establishes a correlation between antibiotic use, especifically aminoglycosides and acute renal failure. The research demonstrates the nephrotoxic effects of aminoglycosides, inducing mitochondrial ETC-complex dysfunction, and renal tissue inflammation in experimental rats. GA’s antioxidant properties restored renal oxidative stress markers, reducing kidney inflammation and injury. Histopathological analysis revealed a significant reduction in renal injury with GA treatment. Additionally, GA demonstrated greater efficacy than Vitamin E in restoring antioxidant potential and mitochondrial enzymes.Conclusion: Consequently, our findings imply that long-term use of GA may be a suitable therapeutic strategy for reducing aminoglycoside toxicity. The current study suggests GA’s potential in treating gentamicin-induced nephrotoxicity and acute renal failure, meriting further investigation using advanced techniques.

Gymnema inodorum (Lour.) Decne is a vegetable local to Chiang Mai Province of Northern Thailand. This study aimed to analyze the antioxidant and phytochemical potential of G. inodorum found in Chiang Mai Province; antioxidant compounds of G. inodorum were tested via DPPH, ABTS and FRAP assays, and total phenolic compound and total flavonoid contents were analyzed. Anti-inflammatory effects were focused on regarding pharmacological potential. The gymnemic acid level was analyzed by HPLC-UV, and other potential chemicals were analyzed by LC-QTOF/MS. The quantifications of gymnemic acid contents analyzed using HPLC-UV showed that the highest gymnemic acid concentrations were found in the air-dried and roasted 1-day-fermented leaf extracts (0.1258 ± 0.0157 μg/mg). The highest free radical scavenging activity via DPPH assay was found in baked leaf extract, with an IC50 of 8.99 mg/mL, and via ABTS assay in baked and roasted leaf extracts, with an IC50 of 1.05 mg/mL. FRAP assays showed the highest free radical scavenging activity for the baked leaf extract, with 0.0085 ± 0.008 mM Fe2+/g sample. The total phenolic contents of fresh G. inodorum leaf extracts obtained with ethanol, methanol and water were 0.19 ± 0.0004, 0.21 ± 0.0010 and 0.10 ± 0.0008 μg GAE/g, respectively. The total flavonoid contents of fresh G. inodorum leaf extracts obtained with ethanol, methanol and water were 74.56 ± 28.00, 71.88 ± 16.11 and 10.74 ± 3.63 μg QE/g, respectively. The LC-QTOF/MS analysis of the fresh G. inodorum leaf extract showed that 6-hydroxykaempferol 7-rutinoside was the most abundant compound. In the study, G. inodorum, a plant local to Northern Thailand, is shown to be a useful plant with high antioxidant and phytochemical potential properties. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is a chronic immune‐mediated disease caused by pancreatic β‐cell dysfunction with consequent severe insulin deficiency. Exacerbated blood glucose levels can cause oxidative stress in the pancreatic β‐cells, which leads to inflammation, and apoptosis resulting in islet dysfunction. Although massive studies have been carried out to elucidate the causative factors for β‐cell damage in diabetes, the therapeutic approach to pancreatic β‐cell damage has not been extensively studied. Hence, the present study has been designed to delineate the role of gymnemic acid (GA) in protecting pancreatic β‐cells in diabetic animals, with special reference to inflammation and apoptosis. Our data revealed that the treatment with GA significantly reverted the alteration in both biochemical and histochemical observations in young diabetic rats. Moreover, treatment with the GA downregulates the expression of proinflammatory markers (nuclear factor‐κB, tumor necrosis factor‐α, interleukin‐[IL]‐6, and IL‐1β), proapoptotic proteins (Bax, cytochrome c, and cleaved caspase‐3), as well as upregulates the expression of antiapoptotic protein Bcl‐2 in diabetic rats. These findings suggest that the anti‐inflammatory and antiapoptotic nature of GA mitigates β‐cell damage in hyperglycemic rats. [ABSTRACT FROM AUTHOR]

Background: A high prevalence of atherosclerotic vascular lesions has been associated with renal disease and diabetes and is a major cause for increasing deaths from cardiovascular disease. The present study aimed to determine the beneficial effects of gymnemic acids on the kidney microvasculature and to establish their antiangiogenic properties that are related to the expression of vascular endothelial growth factor (VEGF) protein of segmental and interlobar arteries in induced diabetic rats. Methods: Rats were divided into five groups including the control group (C), control treated with gymnemic acid (CGM), diabetic animals (DM group) that were rendered diabetic by a single dose [60 mg/kg body weight (BW)] of a streptozotocin (STZ) injection, diabetic rats treated with gymnemic acid (400 mg/kg BW) (GM), and diabetic rats treated with glibenclamide (4 mg/kg BW) (GR). After 8 weeks, kidney tissues were collected for histological analysis. In rats with DM, the segmental arteries exhibited increased wall thickness. The kidney microvasculature was examined using the vascular corrosion casting method. Results: Rats with DM presented a decreasing diameter of segmental and interlobar arteries. They were evidently redeveloped and restored in the GM and GR groups. As determined by immunofluorescence, the expression of VEGF was significantly reduced in both the GM and GR groups. Conclusions: The present study demonstrated that gymnemic acid from Gymnema sylvestre may be a promising medical herb for use in the treatment of diabetes and kidney disease. [ABSTRACT FROM AUTHOR]

• GA increased the relative abundance of beneficial microorganisms Lactobacillus and Lachnoclostridium, and decreased the relative abundance of harmful microorganisms Enterococcus and Bacteroides at genus level in the gut of HFD hamsters. • GA ameliorated HFD-induced gut barrier dysfunction by increasing SCFAs and decreasing gut derived-LPS. • GA ameliorated HFD-induced systemic inflammatory responses by improving gut barrier function. • GA regulated liver and adipose tissue lipid metabolism through TLR4-NF-κB signaling pathway in HFD hamsters. Gut microbiota dysbiosis and gut barrier disruption are key events associated with high-fat diet (HFD)-induced systemic metabolic disorders. Gymnemic acid (GA) has been reported to have an important role in alleviating HFD-induced disorders of glycolipid metabolism, but its regulatory role in HFD-induced disorders of the gut microbiota and gut barrier function has not been elucidated. Here we showed that GA intervention in HFD-induced hamsters increased the relative abundance of short-chain fatty acid (SCFA)-producing microbes including Lactobacillus (P <.05) and Lachnoclostridium (P <.01) in the gut, and reduced the relative abundance of lipopolysaccharide (LPS)-producing microbes including Enterococcus (P <.05) and Bacteroides (P <.05), subsequently improving HFD-induced intestinal barrier dysfunction and systemic inflammation. Specifically, GA intervention reduced mRNA expression of inflammatory cytokines, including IL-1β, IL-6 , and TNF-α (P <.01), increased mRNA expression of antioxidant-related genes, including Nfe2l2, Ho-1 , and Nqo1 (P <.01), and increased mRNA expression of intestinal tight junction proteins, including Occludin and Claudin-1 (P <.01), thereby improving gut barrier function of HFD hamsters. This ameliorative effect of GA on the gut of HFD hamsters may further promote lipid metabolic balance in liver and adipose tissue by regulating the Toll-like receptor 4 (TLR4)-nuclear factor-κB (NF-κB) signaling pathway. Taken together, these results systematically revealed the important role of GA in regulating HFD-induced gut microbiota disturbance and gut barrier function impairment, providing a potential clinical theoretical basis for targeted treatment of HFD-induced microbiota dysbiosis. Gymnemic acid alleviates lipid dysmetabolism by regulating the relative abundance of gut microbes in HFD hamsters. [Display omitted] [ABSTRACT FROM AUTHOR]

Gymnema inodorum (Lour.) Decne or Chiang Da, the local northern Thai vegetable, is renowned for its anti-diabetic and hypoglycemic properties and is highly sought after by the functional food industry. This research investigated the relationship between the physiological characteristics, genetic variation, and chemical compositions of different Chiang Da accessions. Two commercial lines (COM1 and COM2) and eight local accessions (BAC1-8) of Chiang Da were gathered and maintained in the same study plot for the investigation of their morphological characteristics, genetic variation, and nutritional and phytochemical constituents. From the morphological data, the two commercial lines were clearly distinctive with their closely related leaf structures. Random amplification of the polymorphic illustrated the genetic diversity between the local accessions and commercial strains in a similar pattern as described by their morphology characteristics and proximate contents. The phytochemical characteristics, nonetheless, projected the two commercial lines in separate groups. The outcome of this study could be beneficial toward the selection of the Chiang Da strains with specific traits for plant breeding programs of functional food interest.

Gymnema inodorum (Lour.) Decne is a vegetable local to Chiang Mai Province of Northern Thailand. This study aimed to analyze the antioxidant and phytochemical potential of G. inodorum found in Chiang Mai Province; antioxidant compounds of G. inodorum were tested via DPPH, ABTS and FRAP assays, and total phenolic compound and total flavonoid contents were analyzed. Anti-inflammatory effects were focused on regarding pharmacological potential. The gymnemic acid level was analyzed by HPLC-UV, and other potential chemicals were analyzed by LC-QTOF/MS. The quantifications of gymnemic acid contents analyzed using HPLC-UV showed that the highest gymnemic acid concentrations were found in the air-dried and roasted 1-day-fermented leaf extracts (0.1258 ± 0.0157 μg/mg). The highest free radical scavenging activity via DPPH assay was found in baked leaf extract, with an IC50 of 8.99 mg/mL, and via ABTS assay in baked and roasted leaf extracts, with an IC50 of 1.05 mg/mL. FRAP assays showed the highest free radical scavenging activity for the baked leaf extract, with 0.0085 ± 0.008 mM Fe2+/g sample. The total phenolic contents of fresh G. inodorum leaf extracts obtained with ethanol, methanol and water were 0.19 ± 0.0004, 0.21 ± 0.0010 and 0.10 ± 0.0008 μg GAE/g, respectively. The total flavonoid contents of fresh G. inodorum leaf extracts obtained with ethanol, methanol and water were 74.56 ± 28.00, 71.88 ± 16.11 and 10.74 ± 3.63 μg QE/g, respectively. The LC-QTOF/MS analysis of the fresh G. inodorum leaf extract showed that 6-hydroxykaempferol 7-rutinoside was the most abundant compound. In the study, G. inodorum, a plant local to Northern Thailand, is shown to be a useful plant with high antioxidant and phytochemical potential properties.

Stability study on Gymnema sylvestre extract under WHO recommended accelerated and long-term conditions for 6 and 30 months, respectively was carried out by taking gymnemagenin as a marker and by evaluating antidiabetic activity through different models. Gymnemagenin was not detected in any stability sample indicating that gymnemic acids (GAs) remain stable in the extract under the test conditions. The extract and its GA rich fraction exhibited mild α-glucosidase inhibitory activity (18–27%) that remained same during the study. Neither hypoglycemic nor anti-hyperglycemic effect was induced by the extract in normal rats in oral glucose tolerance test. The extract and GA rich fraction showed significant antidiabetic activity in alloxan-induced diabetic rats that remained same in all stability samples. Based on these findings, a shelf-life of at least 30 months is suggested for G. sylvestre extract under long-term conditions, and gymnemagenin as a marker for shelf-life assessment of products derived from the plant. [ABSTRACT FROM AUTHOR]

Gymnema sylvestrae (GS) is a large woody climbing plant that is available in dry forests of India and China. It is also proven for other activities like anti-hemolytic, anti-bacterial and anti-cancer. Present review covers recent updates in research on this plant typically during last 10 years. Also, its characterization and extraction, structure activity relationship, in-vitro pharmacology, in-vivo pharmacology, pharmacodynamics, clinical pharmacology and clinical efficacy, safety and toxicity is discussed in details. Detailed review of available literature on GS indicates it is promising plant for treatment of Type 2 Diabetes Mellitus. GS acts only in presence of pancreas as it acts by stimulation of β cells of langerhans. However, it has also shown hepatotoxic property. [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.

Dental caries and periodontitis are the most common oral disease of all age groups, affecting billions of people worldwide. These oral diseases are mostly associated with microbial biofilms in the oral cavity. Streptococcus gordonii, an early tooth colonizing bacterium and Candida albicans, an opportunistic pathogenic fungus, are the two abundant oral microbes that form mixed biofilms with augmented virulence, affecting oral health negatively. Understanding the molecular mechanisms of the pathogen interactions and identifying non-toxic compounds that block the growth of biofilms are important steps in the development of effective therapeutic approaches. In this in vitro study we report the inhibition of mono-species or dual-species biofilms of S. gordonii and C. albicans, and decreased levels of biofilm extracellular DNA (eDNA), when biofilms were grown in the presence of gymnemic acids (GAs), a non-toxic small molecule inhibitor of fungal hyphae. Scanning electron microscopic images of biofilms on saliva-coated hydroxyapatite (sHA) surfaces revealed attachment of S. gordonii cells to C. albicans hyphae and to sHA surfaces via nanofibrils only in the untreated control, but not in the GAs-treated biofilms. Interestingly, C. albicans produced fibrillar adhesive structures from hyphae when grown with S. gordonii as a mixed biofilm; addition of GAs abrogated the nanofibrils and reduced the growth of both hyphae and the biofilm. To our knowledge, this is the first report that C. albicans produces adhesive fibrils from hyphae in response to S. gordonii mixed biofilm growth. Semi-quantitative PCR of selected genes related to biofilms from both microbes showed differential expression in control vs. treated biofilms. Further, GAs inhibited the activity of recombinant S. gordonii glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Taken together, our results suggest that S. gordonii stimulates the expression of adhesive materials in C. albicans by direct interaction and/or signaling, and the adhesive material expression can be inhibited by GAs.

Dental caries and periodontitis are the most common oral disease of all age groups, affecting billions of people worldwide. These oral diseases are mostly associated with microbial biofilms in the oral cavity. Streptococcus gordonii , an early tooth colonizing bacterium and Candida albicans , an opportunistic pathogenic fungus, are the two abundant oral microbes that form mixed biofilms with augmented virulence, affecting oral health negatively. Understanding the molecular mechanisms of the pathogen interactions and identifying non-toxic compounds that block the growth of biofilms are important steps in the development of effective therapeutic approaches. In this in vitro study we report the inhibition of mono-species or dual-species biofilms of S. gordonii and C. albicans , and decreased levels of biofilm extracellular DNA (eDNA), when biofilms were grown in the presence of gymnemic acids (GAs), a non-toxic small molecule inhibitor of fungal hyphae. Scanning electron microscopic images of biofilms on saliva-coated hydroxyapatite (sHA) surfaces revealed attachment of S. gordonii cells to C. albicans hyphae and to sHA surfaces via nanofibrils only in the untreated control, but not in the GAs-treated biofilms. Interestingly, C. albicans produced fibrillar adhesive structures from hyphae when grown with S. gordonii as a mixed biofilm; addition of GAs abrogated the nanofibrils and reduced the growth of both hyphae and the biofilm. To our knowledge, this is the first report that C. albicans produces adhesive fibrils from hyphae in response to S. gordonii mixed biofilm growth. Semi-quantitative PCR of selected genes related to biofilms from both microbes showed differential expression in control vs. treated biofilms. Further, GAs inhibited the activity of recombinant S. gordonii glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Taken together, our results suggest that S. gordonii stimulates the expression of adhesive materials in C. albicans by direct interaction and/or signaling, and the adhesive material expression can be inhibited by GAs. [ABSTRACT FROM AUTHOR]

• Five new Δ15 oleanane-type gymnemic acids are reported from the leaves of Gymnema sylvestre. • These gymnemic acids are found to truncate the metabolism of carbohydrates via the inhibition of α-glucosidase. • The inhibition of α-glucosidase by these compounds is dose dependent. • Pre-treatment with isolated compounds (1 and 4) significantly blunted the effect of oral sucrose challenge in mice. 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 H 2 SO 4. 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 (IC 50 95 μg/ml). Maximum inhibition was achieved with compound 4 (IC 50 57 μg/ml) followed by 3 (IC 50 62 μg/ml), 1 (IC 50 80 μg/ml), 2 (IC 50 120 μg/ml) and 5 (IC 50 128 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. [ABSTRACT FROM AUTHOR]

Gymnemic acid (GA) is known as the antidiabetic phytoconstituent in Gymnema species, and is used for quality control and standardization of Gymnema products. In Thailand, a number of nutraceutical products of Gymnema inodorum (Lour.) Decne. (GI) are commercially available and this number is increasing. However, standardized GA content information and safety usage guidelines for GI have not been published. The aim of this study was to investigate the amount of GA constituent in GI leaves using mass spectrometry. Leaf samples were randomly collected in the Northern part of Thailand. Total GA was extracted using an ethanolic solution. The calculation of total GA was based on the detection of aglycone gymnemagenin using the liquid chromatography/electrospray ionization mass spectrometry with multiple reaction monitoring. The results showed that GI contained total GA content in range of 0.20-1.44 mg per one kilogram dry leaves. [ABSTRACT FROM AUTHOR]

Gymnema sylvestre, a potential anti-diabetic medicinal plant, is used in many herbal drug formulations. The medicinal properties have been credited to the presence of gymnemic acid, which is effective in controlling blood glucose and lipid levels in the body. Molecular and biochemical variations of seven populations of G. sylvestre were investigated using DNA markers and phytochemical fingerprints of gymnemic acid content. Results obtained through these techniques were used in a comparative analysis and revealed a correlation between genetic variations and biochemical content analysis. Thirteen primers were used for RAPD-PCR analysis revealing 112 bands, of which 62 were found to be polymorphic. The percentage of polymorphic bands detected ranged from 11.1 to 84.6% with an average of 54.2%. The average number of amplified bands per primer was 8.62 while the mean number of polymorphic bands per primer was 5.42. A dendrogram of the genetic similarities among the populations was constructed using the genetic distance coefficients and the seven accessions were clustered into four major groups. The total gymnemic acid content level varied significantly among these groups from 3.84 to 7.12 mg g-1 DW. A principle coordinate analysis confirmed the results of clustering. Maximum yield of gymnemic acid content (7.12 mg g-1 DW) was recorded with L7 accession. Results suggest that there might be a positive correlation between genetic makeup and gymnemic acid content; however, this has to be further investigated by using other molecular approaches. [ABSTRACT FROM AUTHOR]

Gymnemic acid I (GA I) is a bioactive component of Gymnema sylvestre. It is an Indian traditional medicinal herb which has antidiabetic effect. However, the molecular mechanism is remaining to be elucidated. Here, we showed that high glucose promoted the rate of apoptosis, GA I decreased the apoptosis under the high glucose stress. Our further study explored that GA I increased the number of autophagosome and the ratio of light chain 3‐I (LC3‐I)/LC3‐II in MIN‐6 cells under the normal or high glucose stress by the methods of western blot analysis and immunofluorescence. It induced autophagy flux and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase β‐1 (p70 S6K/S6K1), which is a substrate of mTOR. GA I decreased the rate of apoptosis and the activity of caspase‐3 under the high glucose stress. The inhibition of apoptosis and caspase‐3 activity by GA I were increased after treating with autophagy inhibitor in mouse islet β cells MIN‐6. Our data suggested that GA I‐induced autophagy protected MIN‐6 cells from apoptosis under high glucose stress via inhibition the phosphorylation activity of mTOR. 1.GA I protects MIN‐6 cells against high glucose induced apoptosis. It induces autophagy via mTOR pathway.2.This induction of autophagy protects MIN‐6 cells from apoptosis and maintains the mass of β cells. Based on the cytoprotective effects of autophagy, upregulation of autophagy to enhancing β cells surviving may be a potential therapeutic target. [ABSTRACT FROM AUTHOR]

The present study was aimed to evaluate anti-inflammatory and antinociceptive activities of gymnemic acid (GA) in Wistar rats. The different doses of GA were tested for their anti-inflammatory in carrageenaninduced rat paw oedema animal model by using buzzer assisted plethysmograph and antinociceptive activities by tail immersion screening model in organ bath, respectively. It was found that GA at the dose of 100 and 150 mg/kg, p.o, significantly (P<0.01) inhibited the carrageenan-induced rat paw edema and significantly (P<0.01) suppressed the threshold pain of rat by tail immersion method. GA showed significant anti-inflammatory and antinociceptive activities at 2nd and 3rd hr. Further, to know the possible mode of action, we evaluated the effect of GA on castor oil-induced diarrhea. The frequency of stool formation was reduced due to GA in castor oil-induced diarrhea, perhaps due to suppression of prostaglandin, suggesting anti-inflammatory and antinociceptive activities. The current findings demonstrate that the administration of GA at the dose of 100 and 150 mg/kg, by oral route produced significant anti-inflammatory and antinociceptive effects in Wistar rats. [ABSTRACT FROM AUTHOR]

Phytochemical and hypoglycemic effects of two varieties of Gymnema sylvestre were studied. The leaves of Big-leaf (MCL) and the small-leaf (ZMGL) varieties were grown in Uka Tarsadia University, Bardoli, India. Water, ethanol, methanol, petroleum ether, haxane and chloroform were used for phytochemical extraction from the dried leaves. Gymnemic acid was extracted and purified from the two varieties by Thin Layer Chromatography (TLC). Four groups of matured whisker rats (six per group) were induced with high-glucose level. Three groups were treated with standard drug Glibenclamide (5mg/kg), gymnemic acid extracts from MCL and ZMDL respectively while the fourth group served as experimental control. Hypoglycemic activities of extracts were evaluated using animals’ blood sample. Result showed water and methanol are best solvents for phytochemical extraction from the plant and the yield is higher in ZMGL than MCL. Also, gymnemic acid yield varied. From the results, hypoglycemic activities from the animals’ blood revealed that treatments from both MCL and ZMGL are not significantly different from standard drug Glibenclamide. The study concluded that water or methanol is appropriate solvent for phytochemical extraction from G. sylvestre leaves and extract from both lines of the plant could be utilized to reduce blood glucose level

Gymnema inodorum (GI) is an indigenous medicinal plant and functional food in Thailand that has recently helped to reduce plasma glucose levels in healthy humans. It is renowned for the medicinal properties of gymnemic acid and its ability to suppress glucose absorption. However, the effects of gymnemic acids on adipogenesis that contribute to the accumulation of adipose tissues associated with obesity remain unknown. The present study aimed to determine the effects of gymnemic acids derived from GI tea on adipogenesis. We purified and identified GiA-7 and stephanosides C and B from GI tea that inhibited adipocyte differentiation in 3T3-L1 cells. These compounds also suppressed the expression of peroxisome proliferator-activated receptor gamma (Pparγ)-dependent genes, indicating that they inhibit lipid accumulation and the early stage of 3T3-L1 preadipocyte differentiation. Only GiA-7 induced the expression of uncoupling protein 1 (Ucp1) and pparγ coactivator 1 alpha (Pgc1α), suggesting that GiA-7 induces mitochondrial activity and beige-like adipocytes. This is the first finding of stephanosides C and B in Gymnema inodorum. Our results suggested that GiA-7 and stephanosides C and B from GI tea could help to prevent obesity.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder, characterized by chronic anovulation/oligomenorrhea, hyperandrogenism, and insulin-resistance. Moreover, some studies propose a possible association between insulin resistance and hyperhomocysteinemia, which is a significant long-term risk for factor for atherogenesis and chronic vascular damage, especially in situations where insulin levels are increased. Insulin-sensitizing agents are used in the treatment of PCOS: in fact, inositols were shown to have insulin-mimetic properties. Synergic action to myo-inositol is that of gymnemic acids that have antidiabetic, anti-sweetener, and anti-inflammatory activities. Gymnemic acid formulations have also been found useful against obesity due to their ability to delay the glucose absorption in the blood. L-methyl-folate increases peripheral sensitivity to insulin, maintaining folatemia stable, and thus restoring normal homocysteine levels. Unlike folic acid, L-methyl folate has a higher bioavailability, no drug/food interferences, high absorption, and it is stable to UV-A exposure. The aim of our study is to compare the clinical, endocrine, and metabolic parameters in 100 PCOS women treated with myo-inositol, gymnemic acid, and l-methylfolate (Group A) or myo inositol and folic acid only (Group B), continuously for 6 months. From a clinical point of view, it was noticed a more significant improvement of the menstrual cycle regularity and a more significant reduction of BMI in Group A. Moreover, a more significant decrease of total testosterone and increase of SHBG serum levels were noticed in Group A. The metabolic assessment found a more significant decrease of total cholesterol and homocysteine levels; OGTT glycemia and insulinemia values were significantly more improved after treatment with myo-inositol + gymnemic acid. In conclusion, we can state that a good option for the treatment of PCOS is the combined administration of myo-inositol + gymnemic acid + l-methyl-folate, especially for overweight/obese patients with marked insulin resistance and with associated hyperhomocysteinemia. [ABSTRACT FROM AUTHOR]

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 mineral acid. The chromatographic separation of gymnemic acids mixture afforded four new arylated gymnemic acids ( 1 – 4) along with a gymnemasaponin ( 5 ). The compounds were characterized on the basis of extensive spectral data analysis. The arylated compounds ( 1 – 4 ) showed dose dependent inhibition of α-glucosidase that was found to be comparable to acarbose (IC 50 265 μg/ml). Maximum α-glucosidase inhibition was achieved with compound 2 (IC 50 145 μg/ml) followed by 3 (IC 50 220 μg/ml), 1 (IC 50 230 μg/ml) and 4 (IC 50 310 μg/ml). The results revealed that the overall pattern of acyl/aryl substitution and glycosylation of compounds affected their inhibitory activity. The bidesmosidic glycosides ( 2 and 3 ) showed improved potency than the monodesmosidic glycosides ( 1 and 4) possibly because the additional glucose unit in the former facilitated stronger hydrogen bonding at the catalytic site. The current study provides relatively direct evidence of effectiveness of G. sylvestre against hyperglycemia. [ABSTRACT FROM AUTHOR]

Gymnema sylvestre R. Br. (Asclepiadaceae) has been known to posses potential anti-diabetic activity, and the gymnemic acids were reported as the main bioactive components in this plant species. However, the specific components responsible for the hypoglycemic effect still remain unknown. In the present study, the in vitro study revealed that the extract of G. sylvestre exhibited significant inhibitory activity against α-glucosidase with IC50 at 68.70 ± 1.22 μg/mL compared to acarbose (positive control) at 59.03 ± 2.30 μg/mL, which further indicated the potential anti-diabetic activity. To this end, a method based on affinity ultrafiltration coupled with liquid chromatography mass spectrometry (UF-HPLC-MS) was established to rapidly screen and identify the α-glucosidase inhibitors from G. sylvestre. In this way, 9 compounds with higher enrichment factors (EFs) were identified according to their MS/MS spectra. Finally, the structure-activity relationships revealed that glycosylation could decrease the potential antisweet activity of sapogenins, and other components except gymnemic acids in G. sylvestre could also be good α-glucosidase inhibitors due to their synergistic effects. Taken together, the proposed method combing α-glucosidase and UF-HPLC-MS presents high efficiency for rapidly screening and identifying potential inhibitors of α-glucosidase from complex natural products, and could be further explored as a valuable high-throughput screening (HTS) platform in the early anti-diabetic drug discovery stage.

Gymnema sylvestre R. Br. (Asclepiadaceae) has been known to posses potential anti-diabetic activity, and the gymnemic acids were reported as the main bioactive components in this plant species. However, the specific components responsible for the hypoglycemic effect still remain unknown. In the present study, the in vitro study revealed that the extract of G. sylvestre exhibited significant inhibitory activity against α-glucosidase with IC50 at 68.70 ± 1.22 μg/mL compared to acarbose (positive control) at 59.03 ± 2.30 μg/mL, which further indicated the potential anti-diabetic activity. To this end, a method based on affinity ultrafiltration coupled with liquid chromatography mass spectrometry (UF-HPLC-MS) was established to rapidly screen and identify the α-glucosidase inhibitors from G. sylvestre. In this way, 9 compounds with higher enrichment factors (EFs) were identified according to their MS/MS spectra. Finally, the structure-activity relationships revealed that glycosylation could decrease the potential antisweet activity of sapogenins, and other components except gymnemic acids in G. sylvestre could also be good α-glucosidase inhibitors due to their synergistic effects. Taken together, the proposed method combing α-glucosidase and UF-HPLC-MS presents high efficiency for rapidly screening and identifying potential inhibitors of α-glucosidase from complex natural products, and could be further explored as a valuable high-throughput screening (HTS) platform in the early anti-diabetic drug discovery stage. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a chronic disease, typified by hyperglycemia resulting from failures in complex multifactorial metabolic functions, that requires life-long medication. Prolonged uncontrolled hyperglycemia leads to micro- and macro-vascular complications. Although antidiabetic drugs are prescribed as the first-line treatment, many of them lose efficacy over time or have severe side effects. There is a lack of in-depth study on the patents filed concerning the use of natural compounds to manage diabetes. Thus, this patent analysis provides a comprehensive report on the antidiabetic therapeutic activity of 6 phytocompounds when taken alone or in combinations. Four patent databases were searched, and 17,649 patents filed between 2001 and 2021 were retrieved. Of these, 139 patents for antidiabetic therapeutic aids that included berberine, curcumin, gingerol, gymnemic acid, gymnemagenin and mangiferin were analyzed. The results showed that these compounds alone or in combinations, targeting acetyl-coenzyme A carboxylase 2, serine/threonine protein kinase, α-amylase, α-glucosidase, lipooxygenase, phosphorylase, peroxisome proliferator-activated receptor-γ (PPARγ), protein tyrosine phosphatase 1B, PPARγ co-activator-1α, phosphoinositide 3-kinase and protein phosphatase 1 regulatory subunit 3C, could regulate glucose metabolism which are validated by pharmacological rationale. Synergism, or combination therapy, including different phytocompounds and plant extracts, has been studied extensively and found effective, whereas the efficacy of commercial drugs in combination with phytocompounds has not been studied in detail. Curcumin, gymnemic acid and mangiferin were found to be effective against diabetes-related complications. Please cite this article as: DasNandy A, Virge R, Hegde HV, Chattopadhyay D. A review of patent literature on the regulation of glucose metabolism by six phytocompounds in the management of diabetes mellitus and its complications. J Integr Med. 2023; 21(3): 226-235., (Copyright © 2023 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)