B-Type Trimeric Procyanidins Attenuate Nonalcoholic Hepatic Steatosis Through AMPK/mTOR Signaling Pathway in Oleic Acid-Induced HepG2 Cells and High-Fat Diet- Fed Zebrafish.

Abstract

NAFLD is one of the most common and rapidly increasing liver diseases. Procyanidin C1 and procyanidin C2, B-type trimeric procyanidins, show beneficial effects on regulating lipid metabolism. However, the mechanism underlying these effects remain elusive. Therefore, we investigated the anti-NAFLD effects and mechanisms of procyanidin C1 and procyanidin C2 on HFD- induced zebrafish and OA-treated HepG2 cells. Network pharmacology, molecular docking and molecular dynamics simulations were used to predict potential targets and analyze intermolecular forces. The results demonstrated that procyanidin C1 and procyanidin C2 significantly reduce lipid accumulation and oxidative stress in both HFD-induced zebrafish and OA-treated HepG2 cell. And, treatment with procyanidin C1 and procyanidin C2 significantly enhance fatty acid oxidation and improve mitochondria function. Furthermore, procyanidin C1 and procyanidin C2 increased phosphorylated AMPKα levels and inhibited phosphorylated mTOR, along with downstream lipogenic proteins such as SREBP-1c, FAS, ACC, SCD-1 and PPARγ.