Sesamin Protects against APAP-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Inflammatory Response via Deactivation of HMGB1/TLR4/NFκB Signal in Mice.

Acetaminophen (APAP) overdose would lead to liver toxicity and even acute liver failure in severe cases by triggering an inflammatory response and oxidative stress. Sesamin has been reported to possess anti-inflammatory and antioxidant actions in several animal disease models. In the present study, the effects and mechanisms of sesamin on APAP-induced acute liver injury (ALI) were explored. The results showed that pretreatment with sesamin significantly alleviated APAP-induced ALI, as indicated by decreased serum aminotransferase activities, hepatic pathological damages, and hepatic cellular apoptosis. But sesamin has no significant effects on the expression of cytochrome P450 2E1 (CYP2E1), APAP-cysteine adducts (APAP-CYS) production, and glutathione content in the liver of APAP-administered mice. Moreover, APAP-induced liver oxidative stress and inflammatory response also were remarkedly attenuated by sesamin, including reducing hepatic reactive oxygen species levels, promoting antioxidant generation, and inhibiting the expression of TNF-α and IL-1ß, as well as decreasing inflammatory cell recruitment. Notably, sesamin inhibited serum high-mobility group box 1 (HMGB1) releases and blocked hepatic activation of Toll-like receptor 4 (TLR4)-interleukin 1 receptor-associated kinase 3-nuclear factor kappa B (NF-κB) signaling pathway in APAP-administered mice. These findings indicated that sesamin could mitigate APAP-induced ALI through suppression of oxidative stress and inflammatory response, which might be mediated by the deactivation of HMGB1/TLR4/NF-κB signaling in mice.

Chlorogenic acid ameliorated concanavalin A-induced hepatitis by suppression of Toll-like receptor 4 signaling in mice.

Chlorogenic acid (CGA), one of the most abundant dietary polyphenolic compounds, has been reported to exhibit anti-inflammatory ability. However, the hepatoprotective effects and molecular mechanisms of CGA on concanavalin A (Con A)-induced hepatitis have not been explored. In the present study, we found that pretreatment with CGA dose-dependently inhibited the elevation of plasma aminotransferases and alleviated hepatic pathological damage as well as hepatocyte apoptosis in Con A-exposed mice. Additionally, CGA markedly suppressed the production of serum tumor necrosis factor (TNF)-α and interferon (IFN)-γ, alleviated the infiltration of hepatic macrophages, neutrophils, and activated CD4+ T lymphocytes in Con A-primed mice. Moreover, CGA downregulated Con A-induced hepatic expression of adhesion molecules (ICAM-1, VCAM-1 and ELAM-1) mRNA and protein, and inhibited Con A-activated Toll-like receptor (TLR) 4 signal molecules including TLR4, p-IRAK1, p-IκB, and p-p38. Finally, our results also showed that CGA exhibited a therapeutic effect, which CGA posttreatment improved hepatic damage at 1, 3, and 6h after Con A. Taken together, these data suggested that CGA could effectively prevent mice from Con A-induced hepatitis, which might be through suppressing the activation of TLR4 signaling, downregulating the expression of adhesion molecules, and alleviating the infiltration and activation of hepatic leukocytes and the production of pro-inflammatory cytokines.