荭草酮可减轻 LPS 诱导的炎症反应，并抑制巨噬细胞中 NLRP3 炎性体的激活。
Bavachin attenuates LPS-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages.
机构信息
Graduate School of Sport Sciences, Waseda University, Tokorozawa 359-1192, Japan.
Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
出版信息
Phytomedicine. 2019 Jun;59:152785. doi: 10.1016/j.phymed.2018.12.008. Epub 2018 Dec 10.
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, 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 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.
背景
补骨脂素是从 Psoralea corylifolia L. 中分离出来的一种天然产物，已在亚洲国家作为传统药物应用。然而，补骨脂素对 LPS 诱导的炎症和巨噬细胞中 NLRP3 炎性体激活的抗炎作用尚不清楚。
目的
我们研究了补骨脂素对 LPS 激活的小鼠巨噬细胞系 J774A.1 细胞和小鼠腹腔巨噬细胞的抗炎作用。
方法
用 LPS 处理后，用补骨脂素预处理 J774A.1 细胞和小鼠腹腔巨噬细胞。分析细胞培养上清液中 NO、PGE、IL-6 和 IL-12p40 的浓度。用 Western blot 分析 iNOS、COX-2、mPGES-1 和 MAPKs 的表达，用启动子报告基因检测法检测 NF-κB 活性。为了研究 NLRP3 炎性体的激活，用 LPS 孵育 J774A.1 细胞，然后用 ATP 处理后用补骨脂素处理。测量细胞培养上清液中 IL-1β 的浓度。用 Western blot 分析 NLRP3、ASC、caspase-1 和 IL-1β 的表达。用免疫荧光显微镜观察炎性体复合物的形成。
结果
补骨脂素抑制 LPS 诱导的 NO 和 PGE 的产生，并降低 iNOS 和 mPGES-1 的表达。补骨脂素还降低 LPS 诱导的 IL-6 和 IL-12p40 的产生，并降低 MAPKs 和 NF-κB 的激活。此外，补骨脂素抑制 NLRP3 炎性体衍生的 IL-1β 的分泌，减少 caspase-1 的激活，抑制成熟 IL-1β 的表达，并抑制炎性体复合物的形成。此外，补骨脂素还抑制 LPS 刺激的小鼠腹腔巨噬细胞中 NO、IL-6 和 IL-12p40 的产生。
结论
我们的实验结果表明，补骨脂素具有抗炎作用，可减轻 LPS 诱导的炎症，并抑制巨噬细胞中 NLRP3 炎性体的激活。这些结果表明，补骨脂素可能具有治疗炎症性和自身免疫性疾病的潜力。
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