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

Hepatic endothelial function is central to the developmentof nonalcoholicsteatohepatitis (NASH). Curcumin (Cur) is reportedly hepatoprotective,however, it remains unknown whether Cur improves hepatic endothelialfunction in NASH. Additionally, the poor bioavailability of Cur rendersit difficult to elucidate its hepatoprotective effect, hence, itsbiotransformation should be considered. Herein, we investigated theeffects and mechanisms of Cur and its bioconversion on hepatic endothelialfunction against high-fat diet-induced NASH in rats. The results revealedthat Cur improved hepatic lipid accumulation, inflammation, and endothelialdysfunction by inhibiting NF-& kappa;B and PI3K/Akt/HIF-1 & alpha; pathways,however, these effects were weakened via antibiotic addition, whichwas closely related to reduced tetrahydrocurcumin (THC) produce inthe liver and intestinal content. Moreover, THC exerted a better effectthan Cur on restoring liver sinusoidal endothelial cells functionto attenuate steatosis and injury in L02 cells. Thus, these findingsindicate that the effect of Cur on NASH is closely related to hepaticendothelial function improvement with intestinal microbial biotransformation.