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

抄録

Bavachin is a natural product isolated from Psoralea corylifolia L. that has been applied as a traditional medicine in Asia countries. However, the anti-inflammatory effects of bavachin on LPS-induced inflammation and NLRP3 inflammasome activation by macrophages remain unclear. Murine macrophage cell line J774A.1 cells and murine peritoneal macrophages were pre-treated with bavachin following LPS treatment. The concentration of NO in the cell culture supernatant was detected by Griess reagent. The productions of PGE2, IL-6 and IL-12p40 in the cell culture supernatant were examined by ELISA. The expressions of iNOS, COX-2, mPGES-1 and MAPKs were analyzed using Western blotting. NF-kB activity was assayed by 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-1b in the culture supernatant was measured. The expressions of NLRP3, ASC, caspase-1 and IL-1b were analyzed using Western blotting. The formation of inflammasome complex was observed by immunofluorescence microscopy. Bavachin suppressed LPS-induced NO and PGE2 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-kB. Additionally, bavachin suppressed NLRP3 inflammasome-derived IL-1b secretion, decreased caspase-1 activation, repressed mature IL-1b 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. Our experimental results indicated anti-inflammatory effects of bavachin through attenuating LPS-induced inflammation and inhibiting the activation of NLRP3 inflammasome in macrophages. These results suggest that bavachin might have potential in treating inflammatory and autoimmune diseases.