Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Department of Infectious Diseases, Nanjing, Jiangsu, China; Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Infectious Diseases, Nanjing, Jiangsu, China.
Nanjing Hospital of TCM, Department of Infectious Diseases, Nanjing, Jiangsu, China; Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Department of Infectious Diseases, Nanjing, Jiangsu, China.
Int Immunopharmacol. 2020 Apr;81:106195. doi: 10.1016/j.intimp.2020.106195. Epub 2020 Feb 3.
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-1β) 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-1β 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.
黄芩苷（BA）是一种黄酮糖苷，是中药黄芩的成分，用于治疗非酒精性脂肪性肝炎（NASH）。然而，BA 对 NASH 的作用机制尚不清楚。本研究在体外研究了 BA 通过抑制细胞焦亡改善肝细胞的作用。在游离脂肪酸（FFA）暴露 HepG2 细胞的 NASH 细胞模型中，我们发现 BA 可改善 FFA 诱导的肝细胞形态损伤和死亡。然后通过转录组筛选，发现 BA 处理后 NLR 家族含pyrin 结构域蛋白 3（Nlrp3）、gasdermin D（Gsdmd）和白细胞介素-1β（IL-1β）的表达显著下调。进一步分析证实，BA 可降低 NLRP3 和 GSDMD 的水平，以及 IL-1β和 IL-18 的释放，从而减少细胞焦亡。此外，Gsdmd 敲低可减弱 BA 的改善作用。综上所述，BA 可通过阻断 NLRP3-GSDMD 信号通路减少体外肝细胞焦亡。
