Sesquiterpene Lactones from <i>Sigesbeckia glabrescens</i> Possessing Potent Anti-inflammatory Activity by Directly Binding to IKKα/β
Xiaoxu Gao, Xiaofei Shen, Yingying Zheng, Luyao Yang, Xiaoyu Zhang, Gaosheng Hu, Jing‐Ming Jia, An‐Hua Wang
Abstract
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 PGE2, IL-1β, IL-6, and TNF-α in LPS-stimulated RAW264.7 cells. Mechanistically, siegesbeckialide I directly binds to inhibitors of IKKα/β and suppresses their phosphorylation. This leads to the inhibition of IKKα/β-mediated phosphorylation and degradation of inhibitor α of NF-κB (IκBα), as well as the activation of NF-κB signaling.