Swertisin rich fraction from Enicostema littorale ameliorates hyperglycemia and hyperlipidemia in high-fat fed diet and low dose streptozotacin induced type 2 diabetes mellitus in rats.

Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. A lot of research has been done on this plant for its antidiabetic activity. However, there are no reports on flavonoids from E. littorale for its antidiabetic activity and their mechanism of action. Thus, the aim of this study is to evaluate the antidiabetic activity of Swertisin rich flavonoid fraction (SRF) from Enicostema littorale blume and their mechanism of action. Type 2 Diabetes Mellitus rat model was established by inducing insulin resistance using high fat diet and low dose of streptozotacin injection and was authenticated by HOMA index. The antidiabetic effect of SRF was evaluated on diabetic rats to investigate its long term effects on fasting blood glucose, OGTT, weight of rats, insulin, liver profile, lipid profile, kidney profile, histopathology of liver and pancreas. In addition, antioxidant activity by lipid peroxidation and catalase assay, ex vivo assays and hepatic glycogen content were performed to determine its effect on glycogenesis and hepatic glucose production. Furthermore, the mechanism of action of SRF was evaluated by Real time PCR and the mRNA expression was quantified for Glucokinase (GCK), Insulin receptor substrate (IRS-1), Glucose transporter-2 (GLUT-2) and Glucose transporter-4 (GLUT-4) genes. Treatment of diabetic rats with SRF demonstrated significant (p<0.0001) dose dependant hypoglycemic activity as compared to positive control metformin group. A decrease in liver, lipid and kidney function tests was seen as compared to diabetic control indicating normalization of organ function tests. Also, antioxidant activity showed significant decrease in malondialdehyde (MDA) content in liver (p<0.001) as compared to pancreas and increased catalytic activity in liver, kidney, spleen and pancreas. The hepatic glycogen content was significantly (p<0.001) increased in SRF treated rats indicating its inhibition of hepatic glucose production. Furthermore, ex vivo assays showed the significant (p<0.05) increase in glucose uptake by diaphragm. The mRNA expression for GCK, IRS-1, GLUT-2 and GLUT-4 genes showed significant up regulation as compared to diabetic control indicating its mechanism via insulin signalling pathway. The studies suggest that SRF ameliorates the insulin resistance by increasing glucose uptake and sensitizing cells towards insulin via IRS1/PI3K/Akt2 pathway.

Mokashi P ，Bhatt LK ，Khanna A ，Pandita N ... -  《-》

Flavonoids from Enicostema littorale blume enhances glucose uptake of cells in insulin resistant human liver cancer (HepG2) cell line via IRS-1/PI3K/Akt pathway.

Diabetes mellitus has spread over the world with 347 million people affected. Insulin resistance is a main pathogenic event in Type 2 Diabetes Mellitus (T2DM) leading to a reduction in glucose uptake by peripheral tissue and increased hepatic glucose output. In this study, we have isolated four flavonoid rich fractions fraction A (FA), fraction B (FB), fraction C (FC) and fraction D (FD) from Enicostema littorale. All the fractions were preliminary screened for TLC fingerprinting, total flavonoid content. Total eight flavonoids were identified by LC/MS. Insulin resistant HepG2 (IR/HepG2) model was established by inducing insulin resistance in HepG2 cells to investigate the effect of these fractions on IR/HepG2 cell line for their glucose uptake. The results showed the significant dose dependant increase in glucose uptake of cells treated with FD. It showed significant activity at a concentration of 10μg/ml. The LC/MS results of FD demonstrated the presence of C-glycoside Swertisin which could be responsible for the effect. Further, to investigate the mechanism of action, gene expression for insulin receptor substrate 1 (IRS-1), protein kinase B (Akt-2) and glucose transporter 4 (GLUT-4) genes were evaluated by real time PCR. A significant upregulation of these genes was observed in FD treated samples, thereby indicating the enhancement of glucose uptake rate of cells via IRS-1/PI3K/Akt pathway.

Mokashi P ，Khanna A ，Pandita N 《-》

Antidiabetic effect of polysaccharides from Pleurotus ostreatus in streptozotocin-induced diabetic rats.

This study was performed to evaluate the effects of total polysaccharides extracted from Pleurotus ostreatus on type 2 diabetes. Rats were administered with high-fat diet and streptozotocin (STZ) to induce diabetes. The rats were then treated with 100, 200, and 400 mg/kg/d POP or vehicle for 4 weeks. Our experiments indicated that POP reduces hyperglycemia and hyperlipidemia levels, improves insulin resistance, and increases glycogen storage by activating GSK3 phosphorylation and GLUT4 translocation. Moreover, POP reduces the risk of oxidative damage by increasing superoxide dismutase(SOD), catalase(CAT), and glutathione peroxidase(GSH-Px) activities and decreasing malonaldehyde(MDA) level. These results suggest that POP exerts antidiabetic effect on STZ-induced diabetic rats.

Zhang Y ，Hu T ，Zhou H ，Zhang Y ，Jin G ，Yang Y ... -  《-》

Extract of Woodfordia fruticosa flowers ameliorates hyperglycemia, oxidative stress and improves β-cell function in streptozotocin-nicotinamide induced diabetic rats.

Arya A ，Al-Obaidi MM ，Karim RB ，Taha H ，Khan AK ，Shahid N ，Sayem AS ，Looi CY ，Mustafa MR ，Mohd MA ，Ali HM ... -  《-》

Isolated flavonoids from Ficus racemosa stem bark possess antidiabetic, hypolipidemic and protective effects in albino Wistar rats.

Ficus racemosa (FR) has been used for thousands of years in Ayurvedic system of medicine in India and is closely associated with prevention, treatment and cure of various human ailments like obesity and diabetes. It is popularly known as gular. A vast and wide range of chemical compounds like polyphenols, friedelane-type triterpenes, norfriedelane type triterpene, eudesmane-type sesquiterpene including various glycosides had been isolated from this plant. However, no detail studies related to isolation of flavonoids has been reported previously with their antidiabetic, hypolipidemic and toxicological consequences. The present study was undertaken to evaluate antidiabetic, hypolipidemic and toxicological assessments of flavonoids isolated from Ficus racemosa (FR) stem bark. We isolated four flavonoids from stem bark of FR and structures were confirmed by Infrared spectroscopy (IR), Nuclear Magnetic Resonance (NMR) (both 1D and 2D), mass spectroscopy (MS). Later, these flavonoids were administered to streptozotocin (STZ) rats once in a day for a period of seven days at 100mg/kg dose. We measured blood glucose level and body weight changes at different days (1st, 3rd, 5th and 7th days). Serum lipid profiles were also estimated to investigate the hypolipidemic potential of flavonoids in the similar experiment. Various oxidative stress parameters in pancreas and liver and hepatic biomarker enzymes in plasma were also determined to investigate the toxicity potential of isolated flavonoids. Finally, we performed docking studies to find out the mechanism of action. Our results collectively suggested that four flavonoids reduced blood glucose level and restored body weight, signifying antidiabetic action. There were reduction of other lipid profile parameters and increase of high density lipoprotein (HDL) during administration of flavonoids, also signifying hypolipidemic action. Various oxidative stress biomarkers and hepatic enzymes levels were also normalized with respect to diabetic control at the same time. Docking studies revealed that isolated flavonoids showed their antidiabetic potential via binding to PPARγ and GLUT1 receptors. The isolated four flavonoids demonstrated good antidiabetic, hypolipidemic and antioxidant properties in STZ diabetic rats which supported the use of FR stem bark as useful supplementary drug for future antidiabetic therapy.

Keshari AK ，Kumar G ，Kushwaha PS ，Bhardwaj M ，Kumar P ，Rawat A ，Kumar D ，Prakash A ，Ghosh B ，Saha S ... -  《-》