Autophagy activation is one of the survival mechanisms of ethanol-induced hepatitis in mammals. Both Curcumin and Baicalin have anti-inflammatory effects, but the mechanism of their combined action in ethanol-induced hepatitis is still unclear. This study aimed to investigate whether Curcumin combined with Baicalin can resist ethanol-induced p38 MAPK-mediated hepatitis via suppressing TSC1/eIF-2α/ATF4 pathway to activate autophagy. Rats were randomly divided into Control group, EtOH group, EtOH + Curcumin group, EtOH + Baicalin group, and EtOH + Curcumin + Baicalin group. The indicators of liver function and inflammation, and the levels of p38 MAPK and autophagy-related proteins and genes were assayed. Our study found that ethanol increased serum AST, TG, T-CHO levels and liver inflammatory cytokines (TNF-α, IL-1β, INF-γ, NO and iNOS) contents, and also reduced the levels of Beclin1 mRNA and protein, LC3B mRNA and LC3BII/I ratio, but up-regulated the levels of p-p38, P62, p-TSC1, p-eIF-2α and p-ATF4 in rats. Curcumin combined with Baicalin decreased the levels of serum AST, TG, T-CHO and liver inflammatory cytokines, down-regulated the expression of p-p38, P62, p-TSC1, p-eIF-2α and p-ATF4, as well as up-regulated the expression of Beclin1 mRNA and protein, LC3B mRNA and LC3BII/I ratio in rats. Besides, combination therapy was superior to monotherapy. Our results indicated that Curcumin combined with Baicalin can improve ethanol-induced hepatitis by inhibiting p38 MAPK and TSC1/eIF-2α/ATF4 pathway, which may be a potential therapeutic strategy for ethanol-induced hepatitis in the future.

自噬激活是乙醇诱导的哺乳动物肝炎的生存机制之一。姜黄素和黄ical苷均具有抗炎作用，但它们在乙醇诱发的肝炎中的联合作用机制仍不清楚。这项研究旨在探讨姜黄素与黄ical苷联合能否通过抑制TSC1 /eIF-2α/ ATF4途径激活自噬来抵抗乙醇诱导的p38 MAPK介导的肝炎。将大鼠随机分为对照组，EtOH组，EtOH +姜黄素组，EtOH +黄ical苷组和EtOH +姜黄素+黄ical苷组。测定肝功能和炎症的指标，以及p38 MAPK和自噬相关蛋白和基因的水平。我们的研究发现，乙醇会增加血清AST，TG，T-CHO水平和肝炎性细胞因子（TNF-α，IL-1β，INF-γ，NO和iNOS）的含量，大鼠中的p -TSC1，p -eIF-2α和p -ATF4。姜黄素联合黄ical苷可降低血清AST，TG，T-CHO和肝炎性细胞因子的水平，下调p-p38，P62，p - TSC1，p -eIF-2α和p - ATF4的表达，以及上调大鼠Beclin1 mRNA和蛋白，LC3B mRNA和LC3BII / I的表达。此外，联合疗法优于单一疗法。我们的结果表明姜黄素联合黄ical苷可通过抑制p38 MAPK和TSC1 /eIF-2α/ ATF4途径改善乙醇诱发的肝炎，这可能是将来乙醇诱发肝炎的潜在治疗策略。