Methanolic leaf extract of Gymnema sylvestre augments glucose uptake and ameliorates Insulin resistance by upregulating GLUT-4, PPAR- and #947;, adiponectin and leptin levels in vitro

Background:In previous studies, Sharma et al. has already isolated an anti-hyperglycemic compound from the fruit pulp of Eugenia jambolana using HPLC and other chromatographic techniques. However, the effect of antihyperglycemic compound (FIIc) on the expression of Glucose transporters and Kv 1.3 potassium channel in Streptozotocin-Nicotinamide induced diabetic rats has not been studied so far. Objective:To study the effect of HPLC purified herbal anti-hyperglycemic compound (FIIc) on the expression of GLUT-4, GLUT-8 and Kv 1.3 potassium channel in Streptozotocin-Nicotinamide induced diabetic rats.Methods: 24 Male Wistar rats were taken and diabetes was induced in group B, C and D rats (n=6 each) by injecting Streptozotocin at a dose of 45 mg/kg of body weight 15 minutes after the administration of Nicotinamide at a dose of 230 mg/kg of body weight, intraperitoneally to overnight fasted rats. Active compound (FIIc) was orally administered to group C and Pioglitazone to group D at a dose of 20 mg/kg of body weight for 6 weeks respectively. Serum was separated for the estimation of Adiponectin and TNF alpha at week 0 and week 6 of the study. Real time mRNA expression of GLUT-4, GLUT-8 and Kv 1.3 potassium channel was measured and compared between healthy and diabetic control rats. Expression of GLUT-4, GLUT-8 and Kv 1.3 potassium channel was also measured at protein level through Immunohistochemistry and compared between healthy and diabetic controls.Results: After treatment with FIIc for 6 weeks there was a 1.28 folds increase in GLUT-4 mRNA expression in skeletal muscles and 2.67 folds increase in GLUT-8 mRNA expression in liver tissues of group C rats as compared to group B rats. However, Kv 1.3 potassium channel mRNA expression was found to be at par among the four study groups. TNF alpha levels were found to be significantly decreased in group C rats as compared to group B. A slight increase in serum Adiponectin level was observed in group C as compared to group B, which was found to be statistically insignificant. Conclusion:FIIc treatment for 6 weeks significantly increases the expression of GLUT-4, GLUT-8 mRNA expression in liver and skeletal muscles leading to increased peripheral insulin sensitivity.

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“…al. [46]. In our study we also observed increased expression of GLUT-4 in the skeletal muscles of FIIc treated rats.…”

Section: Discussionsupporting

confidence: 79%

Herbal Anti-Hyperglycemic Compound Increases Expression of Glucose Transporter Molecules in Diabetic Rats

Jafri¹,

Sharma²,

Khurana³

et al. 2019

J Diabetes Metab

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“…At 100 μ g concentration, the increase was 1-fold (p<0.05). In a similar previous study conducted, methanolic leaf extract of Gymnema sylvestre (MLGS) demonstrated a significant and dose-dependent increase in glucose uptake in all the concentrations of MLGS studied [ 39 ]. TG at 50 and 100 μ g elevated GLUT2 levels comparable to standard DAG (deacylgymnemic acid).…”

Section: Discussionmentioning

confidence: 81%

In Vitro Antidiabetic Effects of Isolated Triterpene Glycoside Fraction from Gymnema sylvestre

Shenoy

Prashanth

Manonmani

2018

Evidence-Based Complementary and Alternative Medicine

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A triterpene glycoside (TG) fraction isolated and purified from ethanolic extract of Gymnema sylvestre (EEGS) was investigated for blood glucose control benefit using in vitro methods. The HPLC purified active fraction TG was characterized using FTIR, LC-MS, and NMR. The purified fraction (TG) exhibited effective inhibition of yeast α-glucosidase, sucrase, maltase, and pancreatic α-amylase with IC50 values 3.16 ± 0.05 μg/mL, 74.07 ± 0.51, 5.69 ± 0.02, and 1.17 ± 0.24 μg/mL, respectively, compared to control. TG was characterized to be a mixture of triterpene glycosides: gymnemic acids I, IV, and VII and gymnemagenin. In vitro studies were performed using mouse pancreatic β-cell lines (MIN6). TG did not exhibit any toxic effects on β-cell viability and showed protection against H2O2 induced ROS generation. There was up to 1.34-fold increase in glucose stimulated insulin secretion (p<0.05) in a dose-dependent manner relative to standard antidiabetic drug glibenclamide. Also, there was further one-fold enhancement in the expression of GLUT2 compared to commercial standard DAG (deacylgymnemic acid). Thus, the present study highlights the effective isolation and therapeutic potential of TG, making it a functional food ingredient and a safe nutraceutical candidate for management of diabetes.

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“…Presence of phytochemicals like gallic acid [41], ellagic acid [42], berberine [43] and quercetin [44] with reported activation of AMPK pathway substantiated the observed glucose uptake by MD-1 in the absence of insulin. Reported amelioration of insulin resistance by the constituent herbs [45, 46] lends support to the HAEF mediated 2-DG uptake in the presence of insulin.…”

Section: Discussionmentioning

confidence: 91%

MD-1, a poly herbal formulation indicated in diabetes mellitus ameliorates glucose uptake and inhibits adipogenesis – an in vitro study

Telapolu

Kalachavedu

Punnoose³

et al. 2018

BMC Complement Altern Med

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BackgroundType 2 Diabetes (T2D) is a polygenic disease requiring a multipronged therapeutic approach. In the current scenario, the use of polyherbals is increasing among the diabetics. MD-1, a poly herbal formulation is constituted as a mixture of six popular anti diabetic herbs, used in the management of Diabetes mellitus (DM). The physicochemical, biochemical and in vitro efficacy studies have been carried out to ascertain the possible mechanisms underlying the anti-diabetic action of MD-1.MethodsMD-1 was evaluated for residual toxins as per Ayurvedic Pharmacoepia of India (API) procedures. The hydro alcoholic extract of the formulation (HAEF) was evaluated for anti oxidant activity against 2, 2-diphenyl-1-picrylhydrazil (DPPH) and nitric oxide radicals in vitro. The effect of HAEF on carbohydrate digestive enzymes α-glucosidase and α-amylase was studied using biochemical assays. HAEF was studied for its glucose lowering potential in L6 myotubes and 3T3L1 preadipocytes, using 2-deoxy-D-[1-3H] glucose (2-DG) uptake assay. Effect of MD-1 on adipogenesis was evaluated in 3T3L1 adipocytes using oil O red staining. The effect of HAEF on mRNA expression of peroxisome proliferator activated receptor gamma (PPARγ) and glucose transporter 4 (GLUT4) in 3T3L1 adiocytes was investigated by reverse transcriptase polymerase chain reaction (RT-PCR). Statistical analysis was performed by student t-test, ANOVA.ResultsResidual toxins present within the API limits and HAEF demonstrated strong antioxidant potential and significantly inhibited the α-glucosidase (IC50 63.6 ± 0.46 μg/mL) and α-amylase (IC50 242.81 ± 1.26 μg/mL) activity. HAEF significantly (p < 0.05) enhanced the insulin stimulated glucose uptake in both the cell lines studied. Unlike standard pioglitazone (PGZ), HAEF modulated the mRNA expression of PPARγ and GLUT4 (p < 0.0001) in 3T3L1 adipocytes, without inducing adipogenesis.ConclusionPhysicochemical parameters established in the study may serve as reference standards in regular quality control. Absence of residual toxins underpins the safety. The enhanced glucose uptake and favorable modulation of insulin sensitivity through a plausible weak PPARγ agonism is similar to the distinct PPARγ activation pattern of several reported natural compound agonists. The differential binding modes of such dynamic combinatorial ligands within the formulation unlike synthetic ligands like thiozolidinediones (TZD) can be linked to the safe mitigation of diabetic complications by MD-1.

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Methanolic leaf extract of Gymnema sylvestre augments glucose uptake and ameliorates Insulin resistance by upregulating GLUT-4, PPAR- and #947;, adiponectin and leptin levels in vitro

Cited by 17 publications

References 39 publications

Herbal Anti-Hyperglycemic Compound Increases Expression of Glucose Transporter Molecules in Diabetic Rats

Herbal Anti-Hyperglycemic Compound Increases Expression of Glucose Transporter Molecules in Diabetic Rats

In Vitro Antidiabetic Effects of Isolated Triterpene Glycoside Fraction from Gymnema sylvestre

MD-1, a poly herbal formulation indicated in diabetes mellitus ameliorates glucose uptake and inhibits adipogenesis – an in vitro study

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