Inhibitors of Angiotensin-Converting Enzyme in Crude Drugs. II

Abstract

The effects of rhatannin, Chinese gallotannin and tannin fractions isolated from Arecae Semen, Cinnamomi Cortex, Ephedrae Herba, Epimedii Herba, Moutan Cortex, Polygoni avicularis Herba, Potentillae Herba and Rhei Rhizoma on the activities of angiotensin-converting enzyme (ACE) and other six proteases were investigated. These tannin samples had no significant effect on the activity of kallikrein, but all of them inhibited the activities of carboxypeptidase B, leucine aminopeptidase, trypsin and chymotrypsin although to lesser extents as compared to the effects on ACE. On the other hand, all the samples except for Chinese gallotannin and the fraction from Moutan Cortex, enhanced the activity of carboxypeptidase A. All the samples showed non-competitive inhibition patterns with ACE. Rhatannin and the tannin samples obtained from Arecae Semen, Ephedrae Herba, Epimedii Herba, Polygoni avicularis Herba, and Rhei Rhizoma showed more potent inhibitory effects on ACE than the other samples, and their I50values were 3.7, 1.0, 1.9, 2.9, 1.1, and 1.2μg/ml, respectively. The apparent Kivalue of rhatannin for ACE was 5 × 10 7M with Bz-Gly-His-Leu as the substrate, and this value is 5 times and 300 times higher than those of SQ 20881 (Ki= 1 × 10-7m) and SQ 14225 (Ki=1.7 × 10-9m),respectively. Thus, it is suggested that rhatannin and some of the tannin samples obtained from the above crude drugs (which are believed to have hypotensive effects) show high specificity as ACE inhibitors. © 1985, The Pharmaceutical Society of Japan. All rights reserved.