[Effect of astragaloside â
£ on angiotensin â
¡-induced inflammatory response of vascular endothelial cells and mechanism].
Zhongguo Zhong Yao Za Zhi
; 47(21): 5900-5907, 2022 Nov.
Article
en Zh
| MEDLINE
| ID: mdl-36472009
ABSTRACT
This study was designed to determine the inhibitory effect of astragaloside â
£(AS-â
£), a principal bioactive component extracted from the Chinese medicinal Astragali Radix, on the inflammatory response of vascular endothelial cells induced by angiotensin â
¡(Ang â
¡), the most major pathogenic factor for cardiovascular diseases, and to clarify the role of calcium(Ca~(2+))/phosphatidylinosi-tol-3-kinase(PI3K)/protein kinase B(Akt)/endothelial nitric oxide synthase(eNOS)/nitric oxide(NO) pathway in the process. To be specific, human umbilical vein endothelial cells(HUVECs) were cultured in the presence of AS-â
£ with or without the specific inhibitor of NO synthase(NG-monomethyl-L-arginine, L-NMMA), inhibitor of PI3K/Akt signaling pathway(LY294002), or Ca~(2+)-chelating agent(ethylene glycol tetraacetic acid, EGTA) prior to Ang â
¡ stimulation. The inhibitory effect of AS-â
£ on Ang â
¡-induced inflammatory response and the involved mechanism was determined with enzyme-linked immunosorbent assay(ELISA), cell-based ELISA assay, Western blot, and monocyte adhesion assay which determined the fluorescently labeled human monocytic cell line(THP-1) adhered to Ang â
¡-stimulated endothelial cells. AS-â
£ increased the production of NO by HUVECs in a dose-and time-dependent manner(P<0.05) and raised the level of phosphorylated eNOS(P<0.05). The above AS-â
£-induced changes were abolished by pretreatment with L-NMMA, LY294002, or EGTA. Compared with the control group, Ang â
¡ obviously enhanced the production and release of cytokines(tumor necrosis factor-α, interleukin-6), chemokines(monocyte chemoattractant protein-1) and adhesion molecules(intercellular adhesion molecule-1, vascular cellular adhesion molecule-1), and the number of monocytes adhered to HUVECs(P<0.05), which were accompanied by the enhanced levels of phosphorylated inhibitor of nuclear factor-κBα protein and activities of nuclear factor-κB(NF-κB)(P<0.05). This study also demonstrated that Ang â
¡-induced inflammatory response was inhibited by pretreatment with AS-â
£(P<0.05). In addition, the inhibitory effect of AS-â
£ was abrogated by pretreatment with L-NMMA, LY294002, or EGTA(P<0.05). This study provides a direct link between AS-â
£ and Ca~(2+)/PI3K/Akt/eNOS/NO pathway in AS-â
£-mediated anti-inflammatory actions in endothelial cells exposed to Ang â
¡. The results indicate that AS-â
£ attenuates endothelial cell-mediated inflammatory response induced by Ang â
¡ via the activation of Ca~(2+)/PI3K/Akt/eNOS/NO signaling pathway.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Angiotensina II
/
Proteínas Proto-Oncogénicas c-akt
Idioma:
Zh
Revista:
Zhongguo Zhong Yao Za Zhi
Año:
2022
Tipo del documento:
Article
País de afiliación:
China