Astragaloside IV improves homocysteine-induced acute phase endothelial dysfunction via antioxidation.
Astragaloside IV, the major active component extracted from Astragalus membranaceus, exerts multipotent activities under pathophysiological conditions. Hyperhomocysteinemia, an independent risk factor for cardiovascular disease, induces oxidative stress leading to endothelial dysfunction. We investigated the effect of astragaloside IV on acute phase endothelial dysfunction induced by homocysteine. In a concentration-dependent manner, endothelial dysfunction was induced by homocysteine. In organ bath experiment using rat aortic rings, treatment with astragaloside IV resulted in an improvement of the impaired endothelium-dependent vasorelaxation by homocysteine as reflected by the higher maximal vasorelaxation to acetylcholine. However, the presence of N(omega)-nitro-L-arginine methyl ester hydrochloride could abolish the protective effect of astragaloside IV on homocysteine-induced vasomotor dysfunction. In human umbilical vein endothelial cells culture experiment, exposure to astragaloside IV significantly ameliorated the homocysteine-induced inactivation of nitric oxide-nitric oxide synthase signal pathway via reducing oxygen species and increasing the activity of superoxide dismutase. Additionally, pretreatment with superoxide dismutase showed a similar effect to astragaloside IV on attenuation of the homocysteine-induced endothelial dysfunction. These data support the view that astragaloside IV might be advantageous in the treatment of endothelial dysfunction induced by disturbed nitric oxide-nitric oxide synthase pathway due to oxidative stress in hyperhomocysteinemia.
Qiu
Li-Hong
LH
Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University.
Xie
Xian-Ji
XJ
Zhang
Bi-Qi
BQ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000166:cytology; D027885:Astragalus propinquus / Q000737:chemistry*; D018929:Cell Culture Techniques; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D014471:Umbilical Veins / Q000166:cytology; D014652:Vascular Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D000975:Antioxidants; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D012503:Saponins; D014315:Triterpenes; D006710:Homocysteine; D009569:Nitric Oxide; C052064:astragaloside A; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D000109:Acetylcholine