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绿茶、南非路易波士茶和依那普利抑制血管紧张素转换酶的药理学机制——酶动力学研究。

The pharmacological mechanism of angiotensin-converting enzyme inhibition by green tea, Rooibos and enalaprilat - a study on enzyme kinetics.

机构信息

Department of Medical and Health Sciences, Division of Drug Research/Pharmacology, Faculty of Health Sciences, Linköping University, Sweden.

出版信息

Phytother Res. 2012 Apr;26(4):517-21. doi: 10.1002/ptr.3588. Epub 2011 Sep 8.

Abstract

Green tea (Camellia sinensis L.) and Rooibos (Aspalathus linearis Dahlg.) inhibit angiotensin-converting enzyme (ACE) in vitro and in vivo. The ACE inhibitor enalaprilat has been described previously as a competitive inhibitor and sometimes as a non-competitive inhibitor. The aim of this study was to investigate the pharmacological mechanism of ACE inhibition of green tea and Rooibos by enzyme kinetics, and to compare this with enalaprilat. A Michaelis-Menten kinetics and Lineweaver-Burk graph showed mean values of V(max)  = 3.73 µM and K(m)  = 0.71 µM for green tea, of V(max)  = 6.76 µM and K(m)  = 0.78 µM for Rooibos, of V(max)  = 12.54 µM and K(m)  = 2.77 µM for enalaprilat, and of V(max)  = 51.33 µM and K(m)  = 9.22 µM for the PBS control. Incubating serum with green tea or Rooibos saturated with zinc chloride did not change the inhibitory effect. Enalaprilat preincubated with zinc chloride showed a decrease in the inhibitory effect. In conclusion, green tea, Rooibos and enalaprilat seem to inhibit ACE activity using a mixed inhibitor mechanism.

摘要

绿茶(Camellia sinensis L.)和路易波士茶(Aspalathus linearis Dahlg.)在体外和体内均能抑制血管紧张素转换酶(ACE)。先前已有文献报道,依那普利拉是一种竞争性抑制剂,有时也被认为是非竞争性抑制剂。本研究旨在通过酶动力学研究绿茶和路易波士茶抑制 ACE 的药理机制,并与依那普利拉进行比较。米氏动力学和 Lineweaver-Burk 图显示,绿茶的 Vmax 值为 3.73 μM,Km 值为 0.71 μM;路易波士茶的 Vmax 值为 6.76 μM,Km 值为 0.78 μM;依那普利拉的 Vmax 值为 12.54 μM,Km 值为 2.77 μM;PBS 对照组的 Vmax 值为 51.33 μM,Km 值为 9.22 μM。用氯化锌饱和处理的血清孵育绿茶或路易波士茶不会改变抑制作用。用氯化锌预孵育的依那普利拉显示出抑制作用的降低。综上所述,绿茶、路易波士茶和依那普利拉似乎通过混合抑制剂机制抑制 ACE 活性。

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