黄芩苷
脂肪肝
黄芩
体内
上睑下垂
非酒精性脂肪肝
脂肪变性
药理学
化学
纤维化
肝损伤
基因敲除
炎症
生物化学
生物
炎症体
医学
免疫学
病理
内分泌学
疾病
中医药
细胞凋亡
高效液相色谱法
替代医学
生物技术
色谱法
作者
Huilian Shi,Fei Qiao,Weiting Lu,Kaiyue Huang,Yuanyuan Wen,Lifang Ye,Yuanyuan Chen
标识
DOI:10.1016/j.ejphar.2022.175270
摘要
Being at the important pathological stage and the critical treatment period of non-alcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) which is associated with fibrosis, hepatic and liver cancer has become a serious medical problem. As one of the major effective components in Scutellaria baicalensis, baicalin takes on anti-oxidant and anti-inflammatory activities. Nevertheless, its effects on NASH and its underlying molecular mechanism have not been thoroughly understood yet. In previous study, we have clarified baicalin could inhibit pyroptosis of hepatocytes mediated by NLRP3 in vitro, but the verification in vivo and upstream mechanism still need further work. Here the NASH mouse model was induced by feeding with a high fat diet (HFD) for 8-12 weeks. Thereafter, in the following weeks, NASH mice were given with HFD plus baicalin. We, subsequently, examined their hepatic function and inflammatory response and conducted the HE staining of liver samples. Furthermore, the underlying molecular mechanism was revealed through diverse molecular biological experiments including quantitative real-time PCR (qRT-PCR), Western blotting (WB), siRNA and CCK8 assays in HepG2 cells incubated with free fatty acid, and was verified in NASH mice. The in vivo findings indicated that baicalin decreased lipid accumulation and inflammation in the liver tissues of NASH mice, as evidenced by the enhanced NRF2/HO-1 expression and the reduced NLRP3/Caspase1/GSDMD levels, and these factors were involved in the pyroptosis pathway. Meanwhile, baicalin also contributed greatly against oxidative injury. The anti-inflammatory effect of baicalin was confirmed by experiments in vitro. For another, knockdown of NRF2 obviously weakened the protective effects of baicalin and reduced the NLRP3/Caspase1/GSDMD-mediated pyroptosis. This study indicates that baicalin is able to attenuate hepatic cell pyroptosis in vivo and in vitro in the case of NASH by regulating the NRF2/HO-1/NRLP3 pathway.
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