Nobiletin attenuates lipopolysaccharide/D-galactosamine-induced liver injury in mice by activating the Nrf2 antioxidant pathway and subsequently inhibiting NF-κB-mediated cytokine production

作者：Zhenxing He, Xuanfei Li, Hao Chen, Kunlun He, Yiming Liu, Junhua Gong, Jianping Gong · 发表于：Molecular Medicine Reports · 年份：2016 · DOI：10.3892/mmr.2016.5943 · 被引用次数：38 · 研究领域：Bioactive Compounds in Plants、Ginger and Zingiberaceae research、Bioactive natural compounds

Inflammation and oxidative stress serve an important role in the development of lipopolysaccharide/D-galactosamine (LPS/GalN)‑induced acute liver injury. Nobiletin, which is found in high quantities in the peel of citrus fruits, is able to modulate immune responses, including inflammatory response and oxidative stress. The present study aimed to evaluate the protective effects of nobiletin on LPS/GalN‑induced acute liver injury. Male C57BL/6 mice were intraperitoneally treated with nobiletin (50, 100 and 200 mg/kg) 2 h prior to LPS/GalN injection. Liver injury was observed in the LPS/GalN group, as demonstrated by increased levels of serum hepatic enzymes and hepatic inflammatory mediators, as well as by histopathological alterations. Treatment with nobiletin reduced serum alanine aminotransferase and aspartate aminotransferase levels, improved hepatic structure, and suppressed hepatic interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α production 24 h after LPS/GalN exposure. Western blot analysis revealed that nobiletin treatment inhibited inducible nitric oxide synthase and cyclooxygenase‑2 liver expression. In addition, nobiletin suppressed LPS/GalN‑induced phosphorylation and degradation of inhibitor of nuclear factor (NF)‑κB (IκB)α, as well as NF‑κB p65 translocation into the nucleus. Nobiletin also upregulated the expression of nuclear NF‑E2‑related factor 2 (Nrf2) and cytoplasmic heme oxygenase‑1. In conclusion, these results indicate that nobiletin serves a protect...