Curcumin combined with Baicalin attenuated ethanol-induced hepatitis by suppressing p38 MAPK and TSC1/ eIF-2α/ATF4 pathways in rats
2021
Wang, Xiaoxia | Chang, Xuhong | Zhan, Haibing | Li, Chengyun | Zhang, Qiong | Li, Sheng | Sun, Yingbiao
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.
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