Benzothiazole derivatives upregulate SIRT1 and relevant genes in high-fat fed C57BL/6J mice

Abstract

SIRT1 is a protein deacetylase and regulates glucose and lipid metabolism through its deacetylase activity for a range of substrates. Growing evidence suggests that activation of SIRT1 can treat diseases such as type II diabetes and cardiovascular diseases. Therefore, novel activators of SIRT1 have aroused enormous interests among scientists. The aim of present study is to synthesize new compounds as SIRT1 activators and to investigate their effects on SIRT1 and relevant genes. The three compounds: (3-benzothiazol-2-yl) aniline (JHJ1), N-(3-(benzothiazol-2-yl)phenyl)-3,4,5-trimethoxybenzamide (JHJ2), and N-(3-(benzothiazol-2-yl)phenyl)-1H-pyrazo-3-carboxamide (JHJ3) were synthesized and their effects on SIRT1 and relevant genes to regulate glucose and lipid metabolism in high-fat diet fed C57BL/6J mice were also addressed. The results showed that relative mRNA expressions of SIRT1, FoxO1, PPARγ, and PGC-1α were significantly up-regulated in the liver, and the glucose, plasma total-cholesterol, hepatic cholesterol, and total triglyceride concentration were markedly lowered by JHJ1, JHJ2, and JHJ3 supplementation, respectively. These results suggest that benzothiazole derivatives HJ1, JHJ2, and JHJ3 supplementation could modulate the plasma lipids metabolism and blood glucose-lowering action in high-fat fed mice through regulation of SIRT1 and relevant genes.