矽肺
体内
炎症
药理学
纤维化
穿心莲
炎症体
医学
免疫学
穿心莲内酯
化学
生物
病理
生物技术
替代医学
作者
Zhe Song,Li Wang,Yongxia Cao,Zihan Liu,Mingliang Zhang,Zhizi Zhang,Shan Jiang,Rui-Feng Fan,Ting Hao,Ruyue Yang,Bingshun Wang,Zhenzhen Guan,Lina Zhu,Zhentao Liu,Shuya Zhang,Liang Zhao,Zhihao Xu,Haiwei Xu,Gui‐Fu Dai
标识
DOI:10.1016/j.intimp.2022.108539
摘要
Silicosis is an irreversible occupational disease caused by silica particle exposure. Abundant evidences suggest that NLRP3-mediated inflammation acts an essential role in fibrogenesis and the pathogenesis of silicosis. In the current work, we firstly reported that (8R-12S)-isoandrographolide (ISA), a diterpenoid lactone ingredient of Chinese traditional medicinal plant Andrographis paniculata (Burm.f.) Nees, could reduce pulmonary inflammation and fibrosis by inhibiting NLRP3, and thereby ameliorate silicosis. ISA administration significantly alleviated lung injury, and attenuated inflammatory response, EMT, as well as collagen deposition in the lung of silica-induced mice. Further studies verified that ISA inhibited the expressions of NLRP3 inflammasome-related proteins NLRP3, ASC and caspase-1 in vivo and in vitro, leading to the attenuation of inflammation and EMT. Additionally, the molecular docking assay indicated that ISA possibly interacted with the residues of LYS26 and GLU47 of NLRP3, implying that ISA might directly bond to protein NLRP3. Of note, ISA revealed a lower cytotoxicity but more potent therapeutic effect than andrographolide (AD), the major active extract of A. paniculata, which has been traditionally used to treat inflammation-related diseases. Taken together, our study clarified a novel role of ISA in attenuating inflammation and fibrosis in silicosis, and indicated a bright future of ISA as a lead compound for developing therapeutic drug for silicosis.
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