Investigation of Mammal Arginase Inhibitory Properties of Natural Ubiquitous Polyphenols by Using an Optimized Colorimetric Microplate Assay

Abstract

Polyphenols are plant secondary metabolites which possess many positive effects on human health. Although these beneficial effects could be mediated through an increase in nitric oxide synthase activity, little is known regarding the inhibitory effect of polyphenols on mammal arginase, an enzyme which competes with nitric oxide synthase for their common substrate, L-arginine. The aim of the present study was to determine the potential of a series of polyphenols as mammalian arginase inhibitors and to identify some structure-activity relationships. For this purpose, we first developed a simple and cost-effective colorimetric microplate method using commercially-available mammal bovine liver arginase (b-ARG 1). Among the ten tested polyphenolic compounds [chlorogenic acid, piceatannol, resveratrol, (-)-epicatechin, taxifolin, quercetin, fisetin, caffeic acid, quinic acid, and kaempferol], cholorogenic acid and piceatannol exhibited the highest inhibitory activities (IC = 10.6 and 12.1 µM, respectively) but were however less active as ()-(2-Boronoethyl)-L-cysteine (IC = 3.3 µM), used as reference compound. Enzyme kinetic studies showed that both chlorogenic acid and piceatannol are competitive arginase inhibitors. Structural data identified the importance of the caffeoyl (3,4-dihydroxycinnamoyl)-part and of the catechol function in the inhibitory activity of the tested compounds. These results identified chlorogenic acid and piceatannol as two potential core structures for the design of new arginase inhibitors.

Arginase inhibitory and antioxidant activities in Syzygium cumini (L.) Skeels leaves extracts collected from three different locations of java

“…Adding antioxidants may contribute beneficial effect in the therapy since oxidative stress plays a critical role in endothelial function 4 . Previous studies reported that some plant extract rich in polyphenols such as cocoa bean 5 , Caesalpinia sappan 6 , Scutellaria indica 7 , and plant-derived polyphenols such as chlorogenic acid, epicatechin, quercetin 8 exhibited arginase inhibitory effect.…”

Inhibitory Effect on Arginase and Total Phenolic Content Determination of Extracts from Different parts of Melastoma malabathricum L.

“…1 Endothelial dysfunction is primarily due to reduction in Nitric Oxide (NO) bioavailabilty, impairment of endothelium-dependent vasorelaxation caused by a loss of nitric oxide bioactivity in the vessel wall. 2 Endothelial dysfunction can result from and/or contribute to several disease development, as occured in hypertension, diabetes mellitus and hypercholesterolemia.…”

“…2 Endothelial dysfunction can result from and/or contribute to several disease development, as occured in hypertension, diabetes mellitus and hypercholesterolemia. [1][2] Arginase is manganese metalloenzyme. 3 Upregulation of Arginase can reduce the bioavailability of NO through competition between arginase with Nitric Oxide Syhthase (NOS) in using L-arginine as substrate, which can cause endothelial dysfunction.…”

“…3 Upregulation of Arginase can reduce the bioavailability of NO through competition between arginase with Nitric Oxide Syhthase (NOS) in using L-arginine as substrate, which can cause endothelial dysfunction. [1][2] Potent inhibitor arginase such as S-(2-boronoethyl)-L-cysteine (BEC), 2-(S)-amino-6-boronohexanoic acid (ABH)) and (omega)-hydroxy-nor-L-arginine (nor-NOHA) have some problem to be more developed. BEC and ABH might confer a potential toxicity and pharmacokinetic problem due to their boronic acid functionality.…”

“…Previous study showed that phenolic compounds such as quercetin, kaempferol, epicatechin has inhibitory effect on bovine arginase with IC 50 31.2, 179.1, and 19.9 µg/ml. 1 Melastoma malabathricum containing those three phenolic compounds 6 and other phenolic compounds so we hypothesized that extracts from different plant of this plant may have arginase inhibitory effects. The plant were also chosen based on their pharmacological effect on patogenesis some diseases related to upregulation of arginase such as hypertension, 7-8 hyperlipidemia 9 and wound healing.…”