Patchouli alcohol ameliorates acute liver injury via inhibiting oxidative stress and gut-origin LPS leakage in rats.

Abstract Alcoholism represents a predisposing factor for liver-related morbidity and mortality worldwide. Pogostemon cablin has been widely used in China for the treatment of digestive system diseases. Patchouli oil, the major active fraction of Pogostemon cablin, can ameliorate alcohol-induced acute liver injury (ALI). However, patchouli alcohol (PA), a principal bioactive ingredient of PO, exerts a protection against ALI remains elusive. The present work focused on the hepatoprotection of PA against acute ethanol-induced hepatotoxicity in rats. In this study, male Wistar rats orally received PA (10, 20, or 40 mg/kg), PO (400 mg/kg) and silymarin (200 mg/kg) for ten days. On the 8th day, the rats orally received 65% ethanol (10 mL/kg, 6.5 g/kg) every 12 h for 3 days. Results showed that PA was found to reduce alcohol-induced ALI, as evidenced by significantly alleviated histopathological alterations, decreased the elevation of ALT and AST levels, and enhanced the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities. Additionally, PA markedly suppressed ROS levels and increased antioxidant enzyme activities via the CYP2E1/ROS/Nrf2/HO-1 pathway. PA regulated lipid accumulation by markedly inhibiting the expression of lipogenesis-related genes and stimulating that of lipolysis-related genes, which were associated with the activation of the AMPK pathway. What’s more, PA pretreatment also restored acute alcohol-induced alterations in gut barrier function, colonic histopathology, and gut microbiota richness and evenness. PA pretreatment alleviated gut-origin LPS-induced inflammation by inhibiting the MyD88/TLR4/NF-κB signal pathway. In general, PA ameliorates ethanol-induced ALI via restoration of CYP2E1/ROS/Nrf2/HO-1-mediated oxidative stress and AMPK-mediated fat accumulation, as well as alleviation of gut-LPS-leakage-induced inflammation regulated by the MyD88/TLR4/NF-κB signaling pathway.