Rice Bran Phenolic Extract Protects against Alcoholic Liver Injury in Mice by Alleviating Intestinal Microbiota Dysbiosis, Barrier Dysfunction, and Liver Inflammation Mediated by the Endotoxin-TLR4-NF-κB Pathway.

Alcoholic liver injury, known as the most general result of chronic alcohol intake, is induced by inflammatory responses, which is activated by intestine-derived endotoxins formed from intestinal dysbiosis. The hepatoprotective activity of rice bran phenolic extract (RBPE) on ethanol-fed mice was investigated for the first time in this study, and the underlying mechanism was explored from gut microbiota, barrier function, and hepatic inflammation. Mice were fed an alcohol-containing liquid diet alone or in mixture with RBPE for 8 weeks. RBPE treatment mitigated ethanol-induced liver damage, evidenced by the declined lipid profile levels and hepatic function markers. Moreover, ethanol intake induced intestinal microbiota dysbiosis, which was attenuated by RBPE supplementation. RBPE treatment improved the alcohol-induced decrease in the expression of ZO-1, Claudin-1, Claudin-4, and Reg3g, revealing the ameliorative effect of RBPE on intestinal barrier dysfunction. Furthermore, RBPE treatment repressed the alcohol-induced trigger of the hepatic endotoxin-TLR4-NF-κB pathway, followed by the mitigated liver inflammation. The findings indicate that RBPE supplementation ameliorates intestinal microbiota dysbiosis and barrier dysfunction, inactivates the endotoxin-TLR4-NF-κB pathway, and represses inflammatory responses in liver, and therefore, intake of RBPE or brown rice may be an effective way to mitigate alcoholic liver injury.