Astragaloside IV Improves Vasodilatation Function by Regulating the PI3K/Akt/eNOS Signaling Pathway in Rat Aorta Endothelial Cells

Abstract

Coronary heart disease (CHD) remains a major public health burden. Endothelial-dependent coronary artery vasoreactivity is a significant indicator of vascular function. Endothelial dysfunction is characterized by decreased nitric oxide (NO) bioavailability and predicts late cardiovascular events. Astragaloside IV (AGIV) is the main active component of the herb Astragalus membranaceus. Although it shows a significant protective effect against vascular endothelial dysfunction, the mechanisms of AGIV promoting the vascular dilation have not been elucidated. This study investigated the vasodilator effect of AGIV on rat aortic rings and the underlying effect of AGIV via the PI3K/Akt/eNOS signaling pathway. We measured the relaxation of isolated RARs after different concentrations of AGIV treatment. Rat aorta endothelial cells were cultured with different doses of AGIV, dimethylsulfoxide, and NG-nitro L-arginine methyl ester. The expression of phosphorylated (p)-Akt and -endothelial nitric oxide synthase (p-eNOS) were tested by Western blot analysis. The messenger (m)RNA expression of eNOS was quantified by real-time polymerase chain reaction. AGIV exerted a vasodilator effect on the aortic rings and increased the NO content in a concentration-dependent manner. The vasorelaxation was suppressed by an eNOS inhibitor. AGIV regulated the PI3K/Akt/eNOS signaling pathway via phosphorylation of Akt at Ser⁴⁷³ and dephosphorylation of eNOS at Thr⁴⁹⁵. The mRNA expression of eNOS was remarkably upregulated by AGIV. AGIV significantly induced the dilation of the aortic rings, leading to the vasodilator response by enhancing the eNOS release via the PI3K/Akt/eNOS signaling pathway.

Protective Effect of Astragaloside IV on High Glucose-Induced Endothelial Dysfunction via Inhibition of P2X7R Dependent P38 MAPK Signaling Pathway

“…Astragaloside IV (As-IV) is a natural nonsynthetic bioactive saponin extracted from the dried root of Astragalus membranaceus [ 13 ] and was widely observed to exert anti-inflammatory and antioxidation effects in various cells and animal models [ 14 – 17 ]. The potent ability of As-IV to restore endothelial dysfunction has also been demonstrated [ 18 ] which is consistent with our previous reports [ 19 ]. Although there is evidence that As-IV has the potential to prevent endothelial dysfunction, the exact mechanism by which As-IV acts against endothelial dysfunction remains unclear.…”

Astragaloside IV inhibits oxidized low‑density lipoprotein‑induced endothelial damage via upregulation of miR‑140‑3p

“…Our previous findings demonstrated that ASV significantly inhibited epithelial-mesenchymal transition induced by transforming growth factor-β1 during the progression of lung fibrosis (11). In addition, previous findings suggested that ASV induced vasodilation by regulating nitric oxide production in the endothelium (12) and it improvesd vascular endothelial dysfunction induced by hyperglycemia via the toll-like receptor 4/nuclear factor (NF)-κB signaling pathway (13). Although the protective effects of ASV on endothelial dysfunction have been reported, the detailed molecular mechanisms remain unclear.…”

Astragaloside IV Regulates the PI3K/Akt/HO-1 Signaling Pathway and Inhibits H9c2 Cardiomyocyte Injury Induced by Hypoxia–Reoxygenation

“…A recently study showed that, a Chinese herbal medicine extract (TFCC) protects against myocardial injury and enhances cellular antioxidant defense capacity by inducing the phosphorylation of Akt, which subsequently activates the Nrf2/HO-1 signaling pathway. 29) In addition, two studies showed that AS-IV has protective effects on the cardiovascular system by regulating the PI3K/Akt signaling pathway. 30,31) However, whether AS-IV further induces HO-1 expression by regulating the PI3K/Akt signaling pathway and its downstream effectors remains unclear.…”