Baicalin attenuates hepatic injury in non-alcoholic steatohepatitis cell model by suppressing inflammasome-dependent GSDMD-mediated cell pyroptosis
Baicalin attenuates hepatic injury in non-alcoholic steatohepatitis cell model by suppressing inflammasome-dependent GSDMD-mediated cell pyroptosis
复制标题
黄芩苷通过抑制炎症小体依赖性 GSDMD 介导的细胞焦亡减轻非酒精性脂肪性肝炎细胞模型的肝损伤
DOI：
10.1016/j.intimp.2020.106195
复制
发表时间：
2020-04-01
影响因子：
5.6
通讯作者：
Chen, Yuanyuan
中科院分区：
文献类型：
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作者：
Shi, Huilian;Zhang, Yanliang;Chen, Yuanyuan
黄芩苷（Baicalin，BA）是一种黄酮苷类化合物，是治疗非酒精性脂肪性肝炎（NASH）的中草药黄芩的主要成分。但BA对NASH的作用机制尚不清楚。本实验通过体外实验研究了BA对肝细胞的促炎作用。通过游离脂肪酸（free fatty acids，FFA）诱导的NASH HepG 2细胞模型，我们发现BA可以改善FFA诱导的肝细胞形态学损伤和死亡。通过转录组筛选发现，BA处理后，NLR pyrin domain containing 3（Nlrp 3）、gasdermin D（Gsdmd）和白细胞介素-1 β（IL-1 β）的表达显著下调。进一步的分析证实，BA可以降低NLRP 3和GSDMD的水平，以及IL-1 β和IL-18的释放，从而减少焦亡。Gsdmd基因敲低可减弱BA的增效作用。结论：BA可通过阻断NLRP 3-GSDMD信号通路减轻肝细胞的凋亡。
Baicalin (BA), a flavone glycoside, is the constituent of Scutellaria baicalensis, a Chinese herbal medicine used to treat non-alcoholic steatohepatitis (NASH). However, the mechanism of BA on NASH is still not clear. Here, the improving effect of BA on hepatocyte through inhibition of pyroprosis was investigated in vitro. With a cell model of NASH exposing HepG2 cells in free fatty acids (FFA), we revealed that BA could improve hepatocyte from FFA-induced morphological damage and death. And then through transcriptomes screening, a significant down-regulation of NLR pyrin domain containing 3 (Nlrp3), gasdermin D (Gsdmd), andinterleukin-1 beta (IL-1 beta) expression were found after BA treatment. Further analysis confirmed that BA could decrease the levels of NLRP3 and GSDMD, as well as the release of IL-1 beta and IL-18, resulting in the reduction of pyroptosis. Moreover, the improving effect of BA could be attenuated by Gsdmd knockdown. In conclusion, BA can reduce pyroptosis of hepatocyte by blocking NLRP3-GSDMD signaling in vitro.