2. Academic Validation
  3. Astragaloside III activates TACE/ADAM17-dependent anti-inflammatory and growth factor signaling in endothelial cells in a p38-dependent fashion

Astragaloside III activates TACE/ADAM17-dependent anti-inflammatory and growth factor signaling in endothelial cells in a p38-dependent fashion

  • Phytother Res. 2020 May;34(5):1096-1107. doi: 10.1002/ptr.6603.
Haifang Wang 1,  Ruihua Yuan 1,  Qingwen Cao 2,  Mian Wang 1,  Dezhi Ren 3,  Xiaoyan Huang 4,  Min Wu 4,  Linping Zhang 4,  Xiangrong Zhao 4,  Xueping Huo 4,  Yalei Pan 5,  Qinshe Liu 1
Affiliations

Affiliations

  • 1 Shaanxi and Xianyang Key Laboratory of Integrated Traditional and Western Medicine for Prevention and Treatment of Cardiovascular Diseases, Institute of Integrated Medicine, Shaanxi University of Chinese Medicine, Xianyang, China.
  • 2 Division of Medical Management, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, China.
  • 3 Department of Cardiology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, China.
  • 4 Laboratory Center, Shaanxi Provincial People's Hospital, Xi'an, China.
  • 5 Shaanxi Collaborative Innovation Center of Chinese Medicine Resources Industrialization, State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Innovative Drug Research Center, Shaanxi University of Chinese Medicine, Xianyang, China.
PMID: 32197276 DOI: 10.1002/ptr.6603
Abstract

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.

Keywords

Astragaloside III; TNF-α converting enzyme; TNFR1; epidermal growth factor receptor; p38; vascular endothelial cells.

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