The Vascular Effects Of Astragalus Membranaceus Bunge (Leguminosae) And Its Active Compositions

The roots of Astragalus membranaceus Bunge (Leguminosae) are amongst the most popular and important "Qi (pronounce chee) tonifying" adaptogenic herbs in China, their use dates back more than 2000 years, and are recorded in Shen Nong's Materia Medica. According to ethnobotancical data collected in China, A. membranaceus has widely been prescribed for centuries for cardiovascular disease such as viral myocarditis, myocardial infarction and heart failure, because A. membranaceus is alleged to possess the effects of antioxidative damage, immune-stimulation, antiviral infection, and inotropic action. And whether A. membranaceus possesses the accommodative effect on blood vessels has been paid more and more attentions. Some clinical trails have poved that A. membranaceus not only has hypotensive effect, but also it can make angina pectoris in patients with coronary artery disease remitted by 80%, and make the display of electrocardiogram improved by 75%. Additionally, it is also demonstrated in some experiments that A. membranaceus can lower the blood pressure of spontaneously hypertesive rats, but not affect the blood pressure of Wistar Kyoto rats;A. membranaceus can increase the flow of the coronary artery and improve myocardial ischemia of rabbits. The further studies indicate A. membranaceus can relax the vessels of the animal limbs, ears, and renals in vivo, but has no similar effects on visceral vessel. Its underlying mechanism is considered to be associated with neurohumor factors. However, up to now thefollowing problems are still not well answered: 1) Does A. membranaceus posses a direct effect on vessels? 2) If it is ture, what is the underlying mechanism? 3) On earth, what compositions of A. membranaceus take part in the effect on vessels?— * Vascular Effect of Total Extract From Astragalus Membranaceus Bunge. [OBJECTIVE]To verify the effect of total extract of Astragalus Membranaceus Bunge {A. membranaceus) on isolated thoracic aorta in Sprague-Dawley rat. [METHODS]Isometric tension recordings were applied to evaluate the effects of A. membranaceus on resting, phenylephrine (PE)-preconstricting or KCl-preconstricting aortic rings with or without the endothelium. Using the corresponding activator and blocking agent such as L-N(co)-nitro- arginine methyl ester (L-NAME), methyl-thioninium chloride (MC), phosphoramidon (PA), caffeine (CF), and phorbol-12,13-diacetate (PD), the underlying mechnism of vasorelaxation-induced by A. membranaceus was determined. [RESULTS]1 > All doses of A. membranaceus exhibited negligible vasomotor actions on aortic rings with or without endothelium at resting tension.2^ All doses of A. membranaceus had no dilatation-effect on rings stimulated by KC1 with or without endothelium at resting tension.3 -. All doses of A. membranaceus produced dose-dependent relaxation in endothelium- denuded rings. However, in endothelium-intact rings, the low doses of A. membranaceus showed a more significant relaxation than that in denuded ones, while the high dose of A. membranaceus induced a transient contraction.4 > Preincubation of the intact rings with Z-NAME or MC markedly, incompletely inhibited A. membranaceus-'mduced relaxation. And pretreatment of endothelium-intact rings with PA significantly attenuated transient contraction by A. membranaceus.5> In the experiment with Ca2+-free medium, A. membranaceus could inhibit thecontraction induced by PE, but adding CaC^ into the organ bath induced a similar enhancement of contraction by PE. Furthermore, A. membranaceus failed to induce an attenuation of contractile response by PD and CF. [CONCLUSION]A. membranaceus have diphasic effects of relaxation and contraction on the aorta rings. The nitric oxide signaling and Ca2+-handling pathway are involved in the A. membranaceus extract- induced vasodilatation, whilst the effect of transient contraction by A. membranaceus is related with endothelin release.^- * Effect of Homocysteine On Isolated Thoracic Aorta In Sprague-Dawley Rats [OBJECTIVE]To verify the effect of homocysteine (HCY) on isolated thoracic aorta in Sprague-Dawley rat. [METHODS]1 * Isometric tension recordings were applied to evaluate the endothelium-dependent and independent vascular effects of HCY. Using simvastatin (SIM), mevalonate (MV), squalestatin (SQS), squalene (SQE), and superoxide dismutase (SOD), the underlying mechnism of vasorelaxation-impaired by HCY was determined.2 ^ Human umbilical vein endothelial cells (HUVECs) were isolated and cultured. After incubating HUVECs with HCY alone, SIM plus HCY or SQS plus HCY, the content of cholesterol (CHL) or nitric oxide (NO) and the activity of NO synthase (NOS) were detected.[RESULTS]K In a dose and time-dependent manner, incubation with HCY caused an impairment of endothelium-dependent relaxation to acetylcholine (ACH). However, endothelium-independent relaxation to sodium nitroprusside was unaffected by HCY.Additionally, Incubation with HCY increased intra/extra-cellular CHL. Following the change of CHL, the intracellular NOS activity and extracellular NOcontent were reduced.2> The inhibitory effect of HCY on relaxant responses could be completely eliminated by SIM. Using MV to co-incubate the rings together with SIM, the effect of SIM-induced response could be partially counteracted.Additionally, SIM prevented HCY produced-accumulation of CHL in HUVECs and in cultured media. With coincubation of SIM and HCY, the inhibitions of NOS activity and NO content caused by HCY were significantly attenuated.3 > The administration of SQS alone only partially reversed the inhibitory effect of HCY. Moreover, when the coincubating dose of SQE in the organ bath was cumulated, the effect of SQS was fully inverted.Additionally, SQS also reduced accumulation of CHL both in and out HUVECs. However, SQS improved both NOS activity and NO production more slightly than that of SIM.4^ Pretreatment of the intact rings with SOD, the impairment of endothelium-dependent vasorelaxation induced by HCY could be improved completely in a dose dependent manner.Additionally, based on the effect of SQS on HCY-impairment to vasorelaxation, adding extra SOD into the organ bath, the protective effect of SQS could be further potentiated [CONCLUSION]The oxidant effect is associated with the endothelium-dependent vasorelaxant dysfunction caused by HCY. The direct inhibition of NO-NOS system and the indirect inhibition of NO-NOS system via activating CHL pathway by the oxidant effect of HCY are considered to be contributed to the underlying mechanism.J=- > Protective Effects of Total Extract From Astragalus Membranaceus BungeOn Homocysteine-Induced Vasodilation Dysfunction [OBJECTIVE]To verify the protective effects of total extract From A. membranaceus on HCY-induced vasodilation dysfunction[METHODS]According to the result of the HCY-induced impairment of endothelium-dependent vasorelaxant dysfunction, isometric tension recordings were applied to evaluate the effects of A. membranaceus on the relaxation of the aortic rings treated with HCY to ACH. Furthermore, this effect of A. membranaceus was compared with that of SOD. [RESULTS]Preincubation of rings with the total extract from A. membranaceus partially attenuated the relaxant impairment of HCY on endothelium-intact aortic rings in a dose-dependent manner, but this effect was much slighter than that of SOD. [CONCLUSION]The total extract from A. membranaceus can prevent the inhibition of HCY-induced endothelium-dependent relaxation in isolated aortic rings, which may be related to scavenging oxygen free radicals.c?, The Effects of Different Active Compositions From AstragalusMembranaceus Bunge On Vasomotor Function [OBJECTIVE]To determine the active compositions of A. membranaceus specific to vasomotor function. [METHODS]Isometric tension recordings were applied to evaluate the effects of each active composition such as polysaccharide, saponin, and aminobutyric acid from A. membranaceus on PE- preconstricting or HCY-pretreating aortic rings. [RESULTS]1 -. All doses of astragalus polysaccharide (APS), astragalus saponin (ASP), and aminobutyric acid (GABA) exhibited negligible vasomotor actions on aortic rings with or without endothelium precontracted with PE.2^ Similar with the effect of total extract from A. membranaceus preincubation of rings with both APS and ASP partially attenuated the relaxant impairment of HCYon endothelium-intact aortic rings, but GABA had no analogous effect. The order ofthe effect was total extract>ASP> APS> GABA.[CONCLUSION]All of APS, ASP, and GABA alone are not associated with the vasorelaxant effects on aortic rings pretreated by PE, while APS and ASP can prevent the inhibition of Hcy-induced endothelium- dependent relaxation in isolated aortic rings, which may be related to the anti-oxidant effect, and ASP showed the optimal effect.