Antihypertensive effects of tannins isolated from traditional Chinese herbs as non-specific inhibitors of angiontensin converting enzyme.
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.
Liu
Ju-Chi
JC
Division of Cardiovascular Medicine, Taipei Medical University-Wan Fang Hospital, No 111, Hsing Lung Road, Section 3, Wen Shan District, Taipei City 117, Taiwan.
Hsu
Feng-Lin
FL
Tsai
Jen-Chen
JC
Chan
Paul
P
Liu
Jenny Ya-Hsin
JY
Thomas
G Neil
GN
Tomlinson
Brian
B
Lo
Ming-Yu
MY
Lin
Jung-Yaw
JY
D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002712:Chlorides / Q000494:pharmacology; D002918:Chymotrypsin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D006973:Hypertension / Q000188:drug therapy*; D020128:Inhibitory Concentration 50; D008516:Medicine, Chinese Traditional; D009067:Mouthwashes / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D013379:Substrate Specificity; D013634:Tannins / Q000302:isolation & purification / Q000494:pharmacology*; D014357:Trypsin / Q000378:metabolism; D017967:Zinc Compounds / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002712:Chlorides; D004365:Drugs, Chinese Herbal; D009067:Mouthwashes; D013634:Tannins; D017967:Zinc Compounds; C016837:zinc chloride; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D002918:Chymotrypsin; D014357:Trypsin