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Bavachin attenuates LPS-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages
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Bavachin attenuates LPS-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages

Yung-Li Hung, Shu-Chi Wang, Katsuhiko Suzuki, Shih-Hua Fang, Chi-Shuo Chen, Wei-Chung Cheng, Chia-Cheng Su, Hsin-Chih Yeh, Hung-Pin Tu, Po-Len Liu, …
Phytomedicine, 卷.59, 152785
06/2019
PMID: 31009850

摘要

Bavachin Inflammation Macrophage mPGES-1 NLRP3 inflammasome Molecular Medicine Pharmacology Pharmaceutical Science Drug Discovery Complementary and Alternative Medicine
Background: Bavachin is a natural product isolated from Psoralea corylifolia L. that has been applied as a traditional medicine in Asian countries. However, the anti-inflammatory effects of bavachin on LPS-induced inflammation and NLRP3 inflammasome activation by macrophages remain unclear. Purpose: We investigated the anti-inflammatory effects of bavachin on LPS-activated murine macrophage cell line J774A.1 cells and murine peritoneal macrophages. Methods: J774A.1 cells and murine peritoneal macrophages were pre-treated with bavachin following LPS treatment. The concentrations of NO, PGE 2 , IL-6 and IL-12p40 in cell culture supernatant were analyzed. The expressions of iNOS, COX-2, mPGES-1 and MAPKs were analyzed using Western blotting, while NF-κB activity was detected using promoter reporter assay. To examine the activation of NLRP3 inflammasome, J774A.1 cells were incubated with LPS, and then treated with bavachin following treatment with ATP. The concentration of IL-1β in the cell culture supernatant was measured. The expressions of NLRP3, ASC, caspase-1 and IL-1β were analyzed using Western blotting. The formation of inflammasome complex was observed by immunofluorescence microscopy. Results: Bavachin suppressed LPS-induced NO and PGE 2 production, and decreased iNOS and mPGES-1 expression. Bavachin also reduced LPS-induced IL-6 and IL-12p40 production and decreased the activation of MAPKs and NF-κB. Additionally, bavachin suppressed NLRP3 inflammasome-derived IL-1β secretion, decreased caspase-1 activation, repressed mature IL-1β expression, and inhibited inflammasome complex formation. Furthermore, bavachin also suppressed the production of NO, IL-6 and IL-12p40 by LPS-stimulated murine peritoneal macrophages. Conclusion: Our experimental results indicated anti-inflammatory effects of bavachin exhibit attenuation of LPS-induced inflammation and inhibit activation of NLRP3 inflammasome in macrophages. These results suggest that bavachin might have potential in treating inflammatory and autoimmune diseases.

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https://doi.org/10.1016/j.phymed.2018.12.008檢視
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