School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People's Republic of China.
J Nat Prod. 2021 Nov 26;84(11):2808-2821. doi: 10.1021/acs.jnatprod.1c00416. Epub 2021 Nov 2.
Chromatographic fractionation of led to the identification of 10 new sesquiterpene lactones, named siegesbeckialides I-O (-) and glabrescones A-C (-), along with 14 known analogues. An anti-inflammatory activity assay showed that siegesbeckialide I () 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, 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.
对进行色谱分离，得到了 10 种新的倍半萜内酯，分别命名为 siegesbeckialides I-O（-）和 glabrescones A-C（-），以及 14 种已知类似物。抗炎活性测定表明，siegesbeckialide I（）最有效地抑制 LPS 诱导的 RAW264.7 鼠巨噬细胞中 NO 的产生。此外，siegesbeckialide I 抑制 LPS 刺激的 RAW264.7 细胞中 iNOS 和 COX2 的蛋白表达以及 PGE、IL-1β、IL-6 和 TNF-α的释放。在机制上，siegesbeckialide I 直接与 IKKα/β 的抑制剂结合，并抑制其磷酸化。这导致 IKKα/β 介导的 NF-κB（IκBα）抑制剂 α 的磷酸化和降解以及 NF-κB 信号的激活受到抑制。
