Protective Effects Of Astragalus Membranaceus And Its Main Constituents On Vascular Dysfunction Induced By Homocysteine

PART ?:Astragalus membranaceus and its main constituents on the acute endothelial dysfunction induced by homocysteineObjective:This study was designed to investigate the effects of Astragalus membranaceus(AM)and its main components on homocysteine(HCY)induced acute impairment of vascular tone and to explore which underlining mechanism was involved in the protective effect of AM.Methods:Inhibitory effects of HCY and protective effects of the total extract of AM(TEA)and its constituents including Astragalus saponins(ASP),Astragalus polysaccharides(APS),Astragalus total flavonoids(ATF)and Astragaloside IV(AST-IV)on endothelium-dependent relaxation were determined by isometric tension recordings.To explore the underlining mechanism,the cultured Human umbilical vein endothelial cells(HUVECs)were used.The nitric oxide(NO)level,the nitric oxide synthase(NOS)and superoxide dismutase(SOD)activity were assayed with Kit.Furthermore,generation of reactive oxygen species(ROS)was detected by 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate(CM-H2DCF-DA).Results:HCY significantly inhibited endothelium-dependent relaxation with increased ROS levels,reduced SOD and NOS activity,decreased NO levels in HUVECs.TEA,ASP and APS(TEA>ASP>APS)improved the endothelium-dependent relaxation impaired by HCY by reversing the effects of HCY on SOD and NOS activity,ROS and NO levels.AST-IV exerted a similar effect as ASP,while ATF did not show any protective effect.Additionally,partially impaired relaxation by HCY was completely blocked due to the presence of N(?)-nitro-L-arginine-methylester(L-NAME),which could not be further altered by treatment with AM,ASP,APS or AST-IV.Finally,SOD exhibited a further improvement of the protective effects on the endothelium-dysfunction after the treatment of TEA,ASP,APS or AST-IV.Conclusion:This study demonstrated that AM potently protected endothelium-dependent relaxation against the acute injury from HCY through nitric oxide regulatory pathways,in which antioxidation played a key role.ASP may be the most important constituents of AM on the vascular protection.PART ?:Vascular protective effects of Astragalus membranaceus and its main constituents in rats with chronic hyperhomocysteinemiaObjective:Hyperhomocysteinemia(HHcy)is an important factor in cardiovascular disease.However,there is currently no cure available in western medicine for HHcy-evoked cardiovascular disease.The present study explored the vascular protective effects of Astragalus membranaceus(AM),a traditional Chinese medicine.Methods and Results:Rats with HHcy were induced by feeding high-methionine diets and treated with total extract of AM(TEA)and its constituents,including Astragalus saponins(ASP),Astragalus total flavonoids(ATF)and Astragalus polysaccharides(APS).Examination of the rats indicated that TEA and ASP controlled blood pressure and ameliorated HHcy-induced impairment of endothelium-dependent vasorelaxation by increasing the nitric oxide content and nitric oxide synthase activity of the abdominal aorta.Furthermore,they decreased the accumulation of hydrogen peroxide and superoxide anion,and attenuated the inhibition of superoxide dismutase and catalase activities in rats with HHcy.Additionally,TEA and ASP attenuated the HHcy-induced increases of matrix metalloproteinase(MMP)-2 and-9 concentrations.However,similar effects were not observed for ATF and APS.Conclusion:TEA and ASP are beneficial to vascular disease,and their effects may be attributed to protective actions against oxidation,activity of the MMPs and endothelial dysfunction.