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

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. K E Y W O R D SAstragaloside III, epidermal growth factor receptor, p38, TNFR1, TNF-α converting enzyme, vascular endothelial cells

Functional characterization of a cycloartenol synthase and four glycosyltransferases in the biosynthesis of cycloastragenol-type astragalosides from Astragalus membranaceus

“…1 ) has attracted tremendous concern due to its neuroprotective 14 , hepatoprotective 15 , anticancer 16 , and antidiabetic activity 17 ; astragaloside III ( 5 , Fig. 1 ) could be a potential drug candidate for its anti-inflammatory 18 and substantial antiviral 19 activity. However, the low yield and intermittent supply of astragalosides from natural or cultivated sources of A .…”

Analysis of the Composition and Anti-Rheumatoid Arthritis Mechanism of Qintengtongbi Decoction Based on Network Pharmacology

“…All of them show a wide range of bioactivities, such as anti-inflammation and antioxidation, as reported in modern pharmacological studies. [25][26][27][28][29][30][31][32][33] From the perspective of TCM, QJ, WLX, SFT, and QFT work together to dispel wind and dampness, clear collaterals, and stop arthralgia; FJ can clear away heat, relieve dampness, clear collaterals, and alleviate pain; YYH can replenish deficiency, and strengthen the body, thereby removing evil spirits without damaging the body; FZ can drive away cold and dampness; MH can dispel wind and disperse cold, activate Yang, and cure arthralgia; HQ can protect the body, and prevent excessive spread of ephedra; FL can strengthen the spleen and clear dampness; GC can promote blood circulation, regulate the body, and remove arthralgia. The whole prescription has the effect of dispelling wind, removing dampness, dispersing cold, clearing collaterals, and relieving pain.…”