Insulin mimetic action of Aloe Emodin Glycosides from Cassia fistula stimulates glucose transport and storage an in vitro and in vivo approach

Abstract

Diabetes mellitus, the most common multi-factorial disorder in India, currently affects more than 150 million people worldwide and is predicted to affect more than 354 million by the year 2030. Insulin resistance occurs when a normal dose of the hormone insulin is incapable of eliciting metabolic responses. Development of insulin resistance is a multistep process having strong genetic and environmental influences although the exact sequence remains unknown. The present study focuses on the investigation of the anti-diabetic and anti-adipogenic activity of Cassia fistula and identifying the active molecule responsible for these effects using L6 myotubes and 3T3-L1 adipocytes. The glucose uptake analysis carried out in the presence of PI3K and IRTK inhibitors (Wortmannin and Genistein) substantiates the mechanism of action of the extract. Hence CFME was subjected to fractionation, separation and purification. Structural characterization using 1H, 13C NMR and Mass spectral analysis led to the identification of the active compound as Aloe Emodin Glycosides (AEG). HPTLC studies revealed the presence of 6.808% w/w of AEG in CFME. Oral administration of CFME and AEG for a period of 21 days augmented the phosphorylation of insulin downstream regulators such as IRß, IRS1, PI3K, Akt/PKB, GLUT4, GSK3ß and PPARand#947; in the skeletal tissue of the type 2 diabetic rats in comparison to the NPD rats. Further, an improvement in the carbohydrate metabolism in diabetic rats was observed by appropriate regulation of the hepatic enzymes such as hexokinase, glucose-6-phosphatase and fructose 1, 6-bisphosphatase with a concomitant increase in glycogen content. Interestingly, a decrease in the lipid peroxidation and improvement in the anti-oxidants (enzymic and non-enzymic) levels in the liver of diabetic rats on treatment with CFME and AEG was observed. These results suggest that AEG could serve as an interesting candidate in the drug development for the management of diabetes. newline