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Astragaloside III activates TACE/ADAM17‐dependent anti‐inflammatory and growth factor signaling in endothelial cells in a p38‐dependent fashion
Author(s) -
Wang Haifang,
Yuan Ruihua,
Cao Qingwen,
Wang Mian,
Ren Dezhi,
Huang Xiaoyan,
Wu Min,
Zhang Linping,
Zhao Xiangrong,
Huo Xueping,
Pan Yalei,
Liu Qinshe
Publication year - 2020
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6603
Subject(s) - transactivation , signal transduction , cytokine , protein kinase b , epidermal growth factor receptor , p38 mitogen activated protein kinases , cancer research , phosphorylation , microbiology and biotechnology , tumor necrosis factor alpha , autocrine signalling , biology , chemistry , receptor , endocrinology , transcription factor , immunology , mapk/erk pathway , biochemistry , gene
Astragaloside III (AS‐III) is a triterpenoid saponin contained in Astragali Radix and has potent anti‐inflammatory effects on vascular endothelial cells; however, underlying mechanisms are unclear. In this study, we provided the first piece of evidence that AS‐III induced phosphorylation of TNF‐α converting enzyme (TACE) at Thr735 and enhanced its sheddase activity. As a result, AS‐III reduced surface TNFR1 level and increased content of sTNFR1 in the culture media, leading to the inhibition of NF‐κB signaling pathway and attenuation of downstream cytokine gene expression. Furthermore, AS‐III induced TACE‐dependent epidermal growth factor receptor (EGFR) transactivation and activation of downstream ERK1/2 and AKT pathways. Finally, AS‐III induced activation of p38. Both TACE activation and EGFR transactivation induced by AS‐III were significantly inhibited by p38 inhibitor SB203580. Taken together, we concluded that AS‐III activates TACE‐dependent anti‐inflammatory and growth factor signaling in vascular endothelial cells in a p38‐dependent fashion, which may contribute to its cardiovascular protective effect.