Antihypertensive effect of caffeic acid and its analogs through dual renin-angiotensin-aldosterone system inhibition

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• 作者：Khushwant S. Bhullar^a ; Gr&eacute ; goire Lassalle-Claux^b ; Mohamed Touaibia^b ; ¹ ; ^{mohamed.touaibia@umoncton.ca" class="auth_mail} ; H.P. Vasantha Rupasinghe^a ; ² ; ^{vrupasinghe@dal.ca" class="auth_mail}
• 关键词：Hypertension ; Renin ; Angiotensin converting enzyme ; Aldosterone ; Caffeic acid ; Polyphenols
• 刊名：European Journal of Pharmacology
• 出版年：5 May, 2014
• 年：2014
• 卷：730
• 期：Complete
• 页码：125-132
• 全文大小：526 K

文摘

Hypertension is a crucial risk factor for cardiovascular diseases and contributes to one third of global mortality. In addition to conventional antihypertensive drugs such as captopril, naturally occurring phytochemicals and their analogs are used for reducing the risk and occurrence of hypertension. Herein, we demonstrate the possible use of caffeic acid and its derivatives in the treatment of hypertension through multi-target modulation of renin-angiotensin-aldosterone system (RAAS). Caffeic acid along with its nineteen novel derivatives, chlorogenic acid, quercetin and captopril were all investigated for the inhibition of renin and angiotensin converting enzyme (ACE) activities and production of aldosterone. Compound class="boldFont">22 with CH₂CH(Ph)₂ moiety exhibited the strongest renin inhibition (IC₅₀=229 碌M) among all compounds tested (P鈮?.05). Caffeic acid was the weakest renin inhibitor (IC₅₀=5704 碌M) among all the compounds assayed. Similar to renin inhibition, compound class="boldFont">22 (IC₅₀=9.1 碌M) also exhibited about 47 times stronger ACE inhibition compared to the parent compound. Analysis of aldosterone revealed that compound class="boldFont">8 with n-Pr moiety was the strongest modulator of aldosterone production among all the derivatives (P鈮?.05). Toxicity analysis using human fibroblasts (WI-38 cells) confirmed the non-toxic manifestations of caffeic acid and its derivatives in comparison to clinically used drug captopril.