期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 105, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2022.108539
关键词
Isoandrographolide; Silicosis; Pulmonary fibrosis; Inflammation; NLRP3 inflammasome
资金
- Major Science and Technology Projects of Henan Province [201111310400]
- Key Scientific and Technological Research Projects in Henan Province [212102310241]
- National Natural Science Foundation of China [81572049]
- Major Collaborative Innovation Projects in Zhengzhou [18XTZX12011]
This study firstly reported that (8R-12S)-isoandrographolide (ISA) from Andrographis paniculata can reduce pulmonary inflammation and fibrosis by inhibiting NLRP3, improving silicosis. ISA administration alleviated lung injury, attenuated inflammatory response, EMT, and collagen deposition in silica-induced mice. Further studies confirmed that ISA inhibited the expressions of NLRP3 inflammasome-related proteins, leading to the reduction of inflammation and EMT.
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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