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Antihypertensive effects of tannins isolated from traditional Chinese herbs as non-specific inhibitors of angiontensin converting enzyme.

机译:从中草药中提取的丹宁酸作为血管紧张素转化酶的非特异性抑制剂的降压作用。

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The tannins are natural polyphenols, able to precipitate water-soluble alkaloids and possess an inhibitory action on the angiotensin converting enzyme (ACE). We identified 18 polyphenolic compounds (tannins) from Chinese herbs and examined the in vitro effects of these tannins on ACE activity, including determination of the 50% inhibitory concentrations (IC50), specificity and mode of inhibition. We also assessed the in vivo inhibitory effect of the tannins on angiotensin I-induced blood pressure elevation in spontaneously hypertensive rats (SHR). Nine tannins with an IC50 <200 microM for ACE inhibitors were identified belonging to three tannin classes: caffeoylquinates, flavan-3-ols and gallotannins. In vitro, we found caffeoylquinates chelate the ACE zinc cofactor. Two of the flavan-3-ols: epigallocatechin-3-O-gallate and epigallocatechin-3-O-methylgallate, and one of gallotannin: 1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose were non-specific inhibitors because also reduced the activity of trypsin and chymotrypsin. The ACE inhibition of 1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose was also reduced after addition of bovine serum albumin, suggesting a non-specific mode of action. In vivo, 1,2,3,6-tetra-O-galloyl-beta-D-glucose and epigallocatechin-3-O-methylgallate had a strong dose-dependent hypotensive effect reducing the blood pressure significantly in the SHR with infusion of the angiotensin I. These findings indicate that some of the tannins isolated from herbs inhibit ACE activity non-specifically. The ACE inhibitory effect of these tannins may explain the hypotensive effects of some traditional Chinese herbs.
机译:单宁是天然的多酚,能够沉淀水溶性生物碱并对血管紧张素转化酶(ACE)具有抑制作用。我们从中草药中鉴定出18种多酚化合物(单宁),并研究了这些单宁对ACE活性的体外影响,包括测定50%抑制浓度(IC50),特异性和抑制方式。我们还评估了单宁对自发性高血压大鼠(SHR)的血管紧张素I诱导的血压升高的体内抑制作用。鉴定出九种单宁,其ACE抑制剂的IC50 <200 microM,属于三类单宁:咖啡酰奎宁酸酯,黄烷-3-醇和没食子单宁。在体外,我们发现咖啡酰奎宁酸盐与ACE锌辅因子螯合。黄烷-3-醇中的两种:表没食子儿茶素-3-O-没食子酸酯和表没食子儿茶素-3-O-甲基没食子酸酯,没食子单宁中的一种:1、2、3、4、6-五-O-没食子酰基-β-D-葡萄糖是非特异性抑制剂,因为它也降低了胰蛋白酶和胰凝乳蛋白酶的活性。添加牛血清白蛋白后,ACE对1、2、3、4、6-戊基-O-galloyl-β-D-葡萄糖的抑制作用也降低了,表明其作用方式非特异性。在体内,1,2,3,6-四-O-没食子酰基-β-D-葡萄糖和表没食子儿茶素-3-O-甲基没食子酸酯具有很强的剂量依赖性降压作用,通过注入SHR可以显着降低SHR中的血压。这些发现表明,从草药中分离出的某些单宁非特异性地抑制ACE活性。这些单宁的ACE抑制作用可以解释某些传统中草药的降压作用。

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