swertiamarin and Insulin-Resistance

Conventional drugs have limitations due to prevalence of contraindications in PCOS patients. To explore the potential effects of swertiamarin, on abrupted insulin and steroidogenic signaling in human luteinized granulosa cells from PCOS patients with or without insulin resistance.. hLGCs from 8 controls and 16 PCOS patients were classified for insulin resistance based on down regulation of protein expression of insulin receptor-β (INSR- β) as shown in our previous paper. Cells were grouped as control, PCOS-IR and PCOS-NIR, treated with swertiamarin (66 µM) and metformin (1 mM). Expression of key molecules involved in insulin signaling, fat metabolism, IGF system and steroidogenesis were compared between groups.. Swertiamarin significantly (P < 0.05) reversed the expression of INSR-β, PI(3)K, p-Akt, PKC-ζ, PPARγ, (P < 0.01) IRS (Ser 307) and IGF system in PCOS-IR group and was equally potent to metformin. In the same group, candidate genes viz SREBP1c, FAS, ACC-1 and CPT-1 were down regulated by swertiamarin (P < 0.001) and metformin (P < 0.001). Significant upregulation was demonstrated in expression of StAR, CYP19A1, 17β-HSD and 3β-HSD when treated with swertiamarin (P < 0.01) and metformin (P < 0.01) in PCOS-IR followed by increase in 17β-HSD and 3β-HSD enzyme activity along with estradiol and progesterone secretions. However, swertiamarin did not reveal any effect on PCOS-NIR group as compared to metformin that significantly (P < 0.01) reversed all the parameters related to steroidogenesis and down regulated basal expression of insulin signaling genes.. Swertiamarin, presents itself as a potential fertility drug in hLGCs from PCOS-IR patients.

Topics: Female; Granulosa Cells; Humans; Insulin; Insulin Resistance; Metformin; Polycystic Ovary Syndrome

Obesity is a risk factor for many metabolic diseases. Efficient therapeutic strategies are urgently needed. Swertiamarin (STM) prevents obesity and the associated insulin resistance and inflammation. However, the therapeutic effects of STM on preexisting obesity remain unclear. Therefore, in this study we aim to investigate the effects of STM on energy expenditure and fat browning in mice with preexisting obesity. C57BL/6J mice are fed with a high-fat diet (HFD) for 8 weeks to induce obesity and then gavaged (or not) with STM for 10 weeks. The whole-body energy metabolism of mice is examined by indirect calorimetry. The results show that after 10 weeks of treatment, STM markedly prevents HFD-induced weight gain, chronic inflammation, insulin resistance, and hepatic steatosis. STM promotes oxygen consumption and energy expenditure. The level of uncoupling protein 1 is enhanced in the brown and white adipose tissues of STM-treated mice. STM increases the phosphorylation of AMP-activated protein kinase and the expressions of genes involved in fat oxidation, reducing fat deposition in skeletal muscles. Meanwhile, STM does not affect the intestinal microbiotic composition. Overall, STM supplementation may serve as a potential therapy for obesity.

Topics: Adipose Tissue; Adipose Tissue, Brown; Animals; Diet, High-Fat; Energy Metabolism; Inflammation; Insulin Resistance; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Oxidative Stress

Obesity is characterized by low-grade chronic inflammation, which underlies insulin resistance and non-alcoholic fatty liver disease (NAFLD). Swertiamarin is a secoiridoid glycoside that has been reported to ameliorate diabetes and NAFLD in animal models. However, the effects of swertiamarin on obesity-related inflammation and insulin resistance have not been fully elucidated. Thus, this study investigated the effects of swertiamarin on inflammation and insulin resistance in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed a HFD or HFD containing swertiamarin for 8 weeks. Obesity-induced insulin resistance and inflammation were assessed in the epididymal white adipose tissue (eWAT) and livers of the mice. Swertiamarin attenuated HFD-induced weight gain, glucose intolerance, oxidative stress, and insulin resistance, and enhanced insulin signalling in mice. Compared to HFD-fed mice, the swertiamarin-treated mice exhibited increased lipolysis and reduced adipocyte hypertrophy and macrophage infiltration in eWAT. Moreover, swertiamarin alleviated HFD-mediated hepatic steatosis and inflammation by suppressing activation of the p38 MAPK and NF-κB pathways within the eWAT and liver of obese mice. In conclusion, supplementation with swertiamarin attenuated weight gain and hepatic steatosis, and alleviated obesity-associated inflammation and insulin resistance, in obese mice.

Topics: Animals; Chronic Disease; Diet, High-Fat; Dietary Supplements; Inflammation; Insulin Resistance; Iridoid Glucosides; Male; Mice; Mice, Inbred C57BL; Obesity; Pyrones

Swertiamarin, a bitter secoiridoid glycoside, is an antidiabetic drug with lipid lowering activity meliorates insulin resistance in Type 2 Diabetes condition. Therefore, the study was designed to explore the antioxidant and hypolipidemic activity of swertiamarin in ameliorating NAFLD caused due to hepatic lipid accumulation, inflammation and insulin resistance. Steatosis was induced in HepG2 cells by supplementing 1mM oleic acid (OA) for 24h which was marked by significant accumulation of lipid droplets. This was determined by Oil Red O (ORO) staining and triglyceride accumulation. Swertiamarin (25μg/ml) decreased triglyceride content by 2 folds and effectively reduced LDH release (50%) activity by protecting membrane integrity thus, preventing apoptosis evidenced by reduced cleavage of Caspase 3 and PARP1. We observed that swertiamarin significantly increased the expressions of major insulin signaling proteins like Insulin receptor (IR), PI(3)K, pAkt with concomitant reduction in p307 IRS-1. AMPK was activated by swertiamarin action, thus restoring insulin sensitivity in hepatocytes. In addition, qPCR results confirmed OA up-regulated Sterol Regulatory Element Binding Protein (SREBP)-1c and fatty acid synthase (FAS), resulting in increased fatty acid synthesis. Swertiamarin effectively modulated PPAR-α, a major potential regulator of carbohydrate metabolism which, in turn, decreased the levels of the gluconeogenic enzyme PEPCK, further restricting hepatic glucose production and fatty acid synthesis. Cumulatively, swertiamarin targets potential metabolic regulators AMPK and PPAR-α, through which it regulates hepatic glycemic burden, fat accumulation, insulin resistance and ROS in hepatic steatosis which emphasizes clinical significance of swertiamarin in regulating metabolism and as a suitable candidate for treating NAFLD.

Topics: AMP-Activated Protein Kinases; Apoptosis; Caspase 3; Cell Membrane; Enzyme Activation; Fatty Liver; Gene Expression Regulation; Gluconeogenesis; Hep G2 Cells; Hepatocytes; Humans; Inflammation; Insulin; Insulin Resistance; Iridoid Glucosides; Lipogenesis; Oleic Acid; Oxidative Stress; Poly(ADP-ribose) Polymerases; Protective Agents; Pyrones; Reproducibility of Results; Signal Transduction; Triglycerides

Dyslipidaemia is one of the major risk factors for cardiovascular disease in diabetes mellitus. Lipid changes associated with diabetes mellitus are attributed to increases in free fatty acid flux, secondary to insulin resistance. In the present study, we have investigated the beneficial effects of swertiamarin on dyslipidaemic conditions associated with type 2 diabetes in streptozotocin-induced type 2 diabetic rats. Swertiamarin (50 mg/kg, i.p.) administered once a day for 6 weeks resulted in significant (p < 0.001) reductions in serum triglycerides, cholesterol and low-density lipoprotein levels in diabetic animals as compared with diabetic control animals. Serum fasting glucose was significantly (p < 0.05) decreased, moreover, the insulin sensitivity index was significantly (p < 0.05) increased in swertiamarin treated animals. Overall the data suggest that swertiamarin has beneficial effects on diabetic associated complications such as dyslipidaemia.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dyslipidemias; Gentianaceae; Hypoglycemic Agents; Insulin Resistance; Iridoid Glucosides; Lipase; Lipoproteins, LDL; Male; Phytotherapy; Pyrones; Rats; Streptozocin