Inhibitory effect of catechin-related compounds on renin activity

Abstract

Renin is a crucial enzyme in the renin-angiotensin system, and the inhibition of its activity is considered as a useful approach to the treatment of hypertension. The inhibitory effect of catechinrelated compounds on renin was investigated in this work. It was found that epigallocatechin gallate (EGCg) possessed the strongest activity with an IC 50 value of 44.53 μM and acted in an uncompetitive manner. Gallated catechins exerted higher inhibition than the ungallated forms, and gallic acid exhibited an inhibitory potency close to that of epicatechin gallate (ECg). Results indicated that the galloyl moiety and ortho-trihydroxy phenyl structures might be favorable for the renin-inhibitory activity of these compounds.Hypertension is significantly associated with the incidence of various cardiovascular diseases. The renin-angiotensin system (RAS) plays an important role in regulating blood pressure in animals, and its inhibition has been well established as an approach to the treatment of hypertension (15). In this system, renin (EC 3.4.23.15) and angiotensin I-converting enzyme (ACE; EC 3.4.15.1) are two key enzymes. Renin can cleave the N-terminus of angiotensinogen to yield angiotensin I, which is an inactive peptide and may further be processed by ACE to produce angiotensin II, a potent vasoconstrictor. Since the conversion catalyzed by renin is the rate-limiting step, it is thought that direct renin inhibition could lead to better suppression of high blood pressure than ACE inhibition can (2). Although many ACE inhibitors derived from foodstuffs have been identified in the past (7), only a few reports on natural renin inhibitors were available (6,11,20,21). Studies have supported that polyphenol-containing materials such as black and green tea (14), red wine (12), cocoa extract (5, 17) and azuki bean seed coats (13) could reduce blood pressure in several experimental hypertensive models. The mechanisms underlying this effect were proposed to be attributable to vasodilator action, the attenuation of vascular oxidative stress and inflammation, and the ability to reduce arginase-2 activity (18), as well as the inhibitory effect against ACE (1, 3). Nevertheless, to date, not much attention has been paid to their potential renin-inhibitory activities. Recently, researchers found that saponins (8, 20, 21), baicalin (6), and the polyphenolic extracts of two green leafy vegetables (2) showed renin-inhibitory activities, which thus suggested the promising prospect of discovering polyphenolic compounds as candidates for renin inhibitors. Catechins represent a major class of polyphenols and are widely distributed in plants. There are four principal kinds of catechins, that is, epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate; the beneficial effects of these compounds on health have been continually studied (4, 10). In the present work, we investigated whether catechin-related compounds could exert renin-inhibitory activities in vitro and also primarily elucidated their structure-act...

Acute and Sub-Acute Antihypertensive Effects of Syzygium polyanthum Leaf Extracts with Determination of Gallic Acid using HPLC Analysis

“…12 In addition, some in vitro studies have demonstrated renin-inhibitory activity and vasorelaxation effect by gallic acid. Li et al 13 reported that gallic acid possessed inhibitory activity towards renin, an important enzyme that can cleave the angiotensinogen to yield angiotensin I. This is the rate-limiting step in the production of angiotensin II, a potent vasoconstrictor.…”

“…Among the identified compounds, gallic acid were previously shown to have some potentials with respect to antihypertensive action. Oral gallic acid was found to significantly reduce blood pressure of diabetic rats 12 and to exhibit renin-inhibitory 13 and vasorelaxation 14,15 effects. However, none has identified the phytochemicals in aqueous decoction of this plant leaf as traditionally prepared.…”

Epigallocatechin Gallate: A Review of Its Beneficial Properties to Prevent Metabolic Syndrome

“…However, in a recent in vitro study, it has been reported inhibitory properties of EGCG with an inhibitory concentration 50 (IC 50 ) value of 44.53 μM. Furthermore, this study revealed that EGCG acted in an uncompetitive manner and suggested that galloyl moiety and ortho-trihydroxy phenyl structures might be favorable for the renin-inhibitory activity of EGCG [ 138 ]. The beneficial properties of EGCG have been examined on spontaneously hypertensive rats (SHR), a model of hypertension, insulin resistance and obesity.…”

Thermoase-Derived Flaxseed Protein Hydrolysates and Membrane Ultrafiltration Peptide Fractions Have Systolic Blood Pressure-Lowering Effects in Spontaneously Hypertensive Rats

“…The renin-angiotensin-aldosterone system (RAAS), which is an important signaling pathway credited with the regulation of extracellular fluid volume, arterial pressure, and tissue perfusion has received significant attention from investigators recently because of its potential as an excellent target for blood pressure lowering agents [3,4,5,6]. Renin and angiotensin I-converting enzyme (ACE) play key roles in the RAAS pathway; renin is responsible for catalyzing hydrolytic production of the inactive decapeptide angiotensin I (AT-I) from the N -terminus of the plasma protein angiotensinogen in what has been recognized as the initial and rate-determining reaction.…”