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Abstract Title:

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

Abstract Source:

Eur J Pharmacol. 2014 May 5 ;730:125-32. Epub 2014 Mar 11. PMID: 24631256

Abstract Author(s):

Khushwant S Bhullar, Grégoire Lassalle-Claux, Mohamed Touaibia, H P Vasantha Rupasinghe

Article Affiliation:

Khushwant S Bhullar

Abstract:

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 22 with CH2CH(Ph)2 moiety exhibited the strongest renin inhibition (IC50=229µM) among all compounds tested (P≤0.05). Caffeic acid was the weakest renin inhibitor (IC50=5704µM) among all the compounds assayed. Similar to renin inhibition, compound 22 (IC50=9.1µM) also exhibited about 47 times stronger ACE inhibition compared to the parent compound. Analysis of aldosterone revealed that compound 8 with n-Pr moiety was the strongest modulator of aldosterone production among all the derivatives (P≤0.05). Toxicity analysis using human fibroblasts (WI-38 cells) confirmed the non-toxic manifestations of caffeic acid and its derivatives in comparison to clinically useddrug captopril.

Study Type : In Vitro Study

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