Rice Bran Phenolic Extract Confers Protective Effects against Alcoholic Liver Disease in Mice by Alleviating Mitochondrial Dysfunction via the PGC-1α-TFAM Pathway Mediated by microRNA-494-3p

The initiation and development of alcoholic liver disease (ALD) is mediated, at least partly, by mitochondria dysfunction, which is regulated by PPAR gamma coactivator-1a (PGC-1 alpha) via mitochondria transcription factor A (TFAM). Then, PGC-1 alpha expression was regulated by several microRNAs. This research investigated the hepatoprotective effects of the rice bran phenolic extract (RBPE) on mice fed with an ethanol-containing diet via the microRNAs-PGC-1a-TFAM signal pathway. RBPE treatment protected against alcoholic liver injury, as indicated by decreased serum aminotransferase activities and hepatic triglyceride accumulation, together with alleviated oxidative stress in serum and the liver. RBPE treatment alleviated ethanol-induced mitochondrial dysfunction through altering the membrane potential, mtDNA content, and respiratory chain complex enzyme activities in mitochondria, resulting in increased hepatic ATP production. Decreased cytoplasmic cytochrome c contents, caspase-3 activity, and Bax/BcI-2 ratio were detected in the liver of RBPE-treated mice, indicating that the RBPE might inhibit ethanol-induced hepatocellular apoptosis. Furthermore, ethanol-induced decreases in the mRNA and protein expression of PGC-la and TFAM were remarkably alleviated in RBPE-treated mice. RBPE treatment to ethanol-fed mice could also downregulate the expression of microRNA-494-3p, which regulates PGC-1 alpha expression directly. Therefore, the RBPE might exert protection against ALD by alleviating mitochondrial dysfunction and the resulting hepatocyte apoptosis via the PGC-1 alpha-TFAM signal pathway mediated by microRNA-494-3p.