Syzygium cumini ameliorates high fat diet induced glucose intolerance, insulin resistance, weight gain, hepatic injury and nephrotoxicity through modulation of PTP1B and PPARγ signaling

Abstract Metabolic disorders are majorly associated with insulin resistance and an impaired glucose tolerance. Since, many of the currently available drugs exhibit adverse effects and are resistant to therapies, natural products are a promising alternate in the alleviation of complex metabolic disorders. In the current study, Syzygium cumini methanolic extract (SCE) was investigated for its anti‐diabetic and anti‐adipogenic potential using C57BL/6 mice fed on high fat diet (HFD). The HFD fed obese mice were treated with 200 mg/kg SCE and compared with positive controls Metformin, Pioglitazone and Sodium Orthovanadate. The biometabolites in SCE were characterized using Fourier transform infrared and gas chromatography and mass spectroscopy. A reduction in blood glucose levels with improved insulin sensitivity and glucose tolerance was observed in SCE‐treated HFD obese mice. Histopathological and biochemical investigations showed a reduction in hepatic injury and nephrotoxicity in SCE‐administered HFD mice. Results showed inhibition of PTP1B and an upregulation of IRS1 and PKB‐mediated signaling in skeletal muscle. A significant decrease in lipid markers such as TC, TG, LDL‐c and VLDL‐c levels were observed with increased HDL‐c in SCE‐treated HFD mice. A significant decrease in weight and adiposity was observed in SCE‐administered HFD mice in comparison to controls. This decrease could be due to the partial agonism of PPARγ and an increased expression of adiponectin, an insulin sensitizer. Hence, the dual‐modulatory effect of SCE, partly due to the presence of 26% Pyrogallol, could be useful in the management of diabetes and its associated maladies.