Preventive effect of salicin ether against type-2 diabetes mellitus through targeting PPARγ-regulated gene expression

Abstract

Diabetes mellitus is the syndrome associated with metabolism having complicated pathogenesis and its morbidity rate is rapidly increasing every year. The present study investigated the preventive effect of salicin ether against type-2 diabetes and explored the underlying mechanism. Salicin ether reduced PPARγ-LBD level and transcriptional property of RXRα-PPARγ in 293T cells. The rosiglitazone significantly (p<0.01) increased grease droplet accumulation in adipocytes in comparison to control adipocytes. Increased grease droplet accumulation by rosiglitazone in adipocytes was reversed on treatment with salicin ether in dose-dependent manner. Salicin ether treatment of the adipocytes effectively suppressed rosiglitazone induced expression of FAS, C/EBPα, aP2, and HMG-CoA genes. Treatment of the adipocytes with salicin ether led to a prominent decrease in rosiglitazone mediated increase in aP2, CHIP, and C/EBPα protein expression. The inhibitory effect of rosiglitazone on expression of p-Akt/t-Akt, PPARa, p-FoxO1/t-FoxO1, and p-AMPK/t-AMPK was significantly (p<0.01) alleviated in the adipocytes by salicin ether. In summary, the present study demonstrated that salicin ether suppressed PPARγ activity and adipocyte differentiation. Moreover, the activation of FoxO1/Akt/AMPK was up-regulated and FAS/EBPα/aP2/HMG-CoA level inhibited by salicin ether in the adipocytes. Thus, salicin ether may be studied further for possible role in the treatment of diabetes.