Tetracera asiatica flavonoids attenuate alcohol-induced liver injury by suppressing oxidative stress and inflammation mediated by the Keap-1/Nrf2/HO-1, NF-κB/MAPK and PERK/Nrf2 signaling pathways in alcoholic liver injury rats.

Alcoholic liver disease is regarded as a leading reason for liver cirrhosis. This study aimed to investigate the protective effect of tetracera asiatica flavonoids (TAF) on alcoholic liver injury (ALI) and explore the associated mechanisms. An ALI rat model was established and then divided into four groups, including ALI group, low-dose TAF (l-TAF) group, medium-dose TAF (m-TAF) group, and high-dose TAF (h-TAF) group. Levels of ALT, AST, ALB, SOD, MDA, NO, CAT, TG, TNF-α, IL-1β, Nrf2, Keap1, HO-1, NQO-1, and GSH-Px were measured in ALI rats in different groups. Pathological changes and inflammatory infiltration were examined using HE staining. Western blot was used to detect expressions of Nrf2, MAPK p38, PERK, NF-κB, ERK1/2 and anti-JNK1/2/3. The results showed that TAF protected against alcoholic liver injury in ALI rats by decreasing ALT and AST levels and inhibiting inflammatory response. TAF significantly reversed alcohol-induced increase in NO (P < 0.05), and remarkably decreased levels of TNF-α (P < 0.001) and IL-1β (P < 0.01), compared with the ALI group. TAF significantly increased the transcription of Nrf2, Keap1, HO-1, NQO-1 and GSH-Px gene (all P < 0.05) and inhibited the alcohol-induced upregulation of MAPK p38 expression (P < 0.001), p-NF-κB/NF-κB ratio (P < 0.001), p-ERK/1/2/ERK1/2 ratio (P < 0.05), and p-JNK1/2/3/JNK1/2/2 ratio (P < 0.05), compared with the ALI group (all P < 0.001). TAF obviously reversed effects of ALI modeling, and remarkably downregulated the expression of PERK and upregulated Nrf2 (all P < 0.001) compared with the ALI rats. In conclusion, TAF attenuates alcohol-induced livery injury through suppressing Keap-1/Nrf2/HO-1, NF-κB/MAPK and PERK/Nrf2 signaling pathways mediated oxidative stress and inflammation in ALI rats.