Curcumin Alleviates High-fat Diet-induced Nonalcoholic Steatohepatitis via Improving Hepatic Endothelial Function with Microbial Biotransformation in Rats.

ABSTRACT

Hepatic endothelial function is central to the development of nonalcoholic steatohepatitis (NASH). Curcumin (Cur) is reportedly hepatoprotective, however, it remains unknown whether Cur improves hepatic endothelial function in NASH. Additionally, the poor bioavailability of Cur renders it difficult to elucidate its hepatoprotective effect, hence, its biotransformation should be considered. Herein, we investigated the effects and mechanisms of Cur and its bioconversion on hepatic endothelial function against high-fat diet-induced NASH in rats. The results revealed that Cur improved hepatic lipid accumulation, inflammation, and endothelial dysfunction by inhibiting NF-κB and PI3K/Akt/HIF-1α pathways, however, these effects were weakened via antibiotic addition, which was closely related to reduced tetrahydrocurcumin (THC) produce in the liver and intestinal content. Moreover, THC exerted a better effect than Cur on restoring liver sinusoidal endothelial cells function to attenuate steatosis and injury in L02 cells. Thus, these findings indicate that the effect of Cur on NASH is closely related to hepatic endothelial function improvement with intestinal microbial biotransformation.