Sesquiterpene Lactones from Sigesbeckia glabrescens Possessing Potent Anti-inflammatory Activity by Directly Binding to IKKα/β
Sesquiterpene Lactones from Sigesbeckia glabrescens Possessing Potent Anti-inflammatory Activity by Directly Binding to IKKα/β
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DOI：
10.1021/acs.jnatprod.1c00416
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发表时间：
2021-11-02
影响因子：
5.1
通讯作者：
Wang, Anhua
中科院分区：
文献类型：
--
作者：
Gao, Xiaoxu;Shen, Xiaofei;Wang, Anhua
Chromatographic fractionation of Sigesbeckia glabrescens led to the identification of 10 new sesquiterpene lactones, named siegesbeckialides I-O (1-7) and glabrescones A-C (8-10), along with 14 known analogues. An anti-inflammatory activity assay showed that siegesbeckialide I (1) most potently inhibited LPS-induced NO production in RAW264.7 murine macrophages. Furthermore, siegesbeckialide I suppressed the protein expression of iNOS and COX2, as well as the release of PGE(2), IL-1 beta, IL-6, and TNF-alpha in LPS-stimulated RAW264.7 cells. Mechanistically, siegesbeckialide I directly binds to inhibitors of IKK alpha/beta and suppresses their phosphorylation. This leads to the inhibition of IKK alpha/beta-mediated phosphorylation and degradation of inhibitor a of NF-kappa B (I kappa B alpha), as well as the activation of NF-kappa B signaling.
