Planta Med 2018; 84(05): 277-295
DOI: 10.1055/s-0044-100398
Georg Thieme Verlag KG Stuttgart · New York

Phenolic Compounds as Arginase Inhibitors: New Insights Regarding Endothelial Dysfunction Treatment

Bruno Rodrigo Minozzo
1  Department of Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa, Paraná, Brazil
Daniel Fernandes
2  Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
Flávio Luís Beltrame
1  Department of Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa, Paraná, Brazil
› Author Affiliations
Further Information

Publication History

received 05 August 2017
revised 09 December 2017

accepted 31 December 2017

Publication Date:
17 January 2018 (online)


Endothelial dysfunction is characterised by the low bioavailability of nitric oxide with a relevant negative impact on the nitric oxide/cGMP pathway. The loss of nitric oxide/cGMP signaling may be caused by an increased arginase activity. Plant-derived substances, especially polyphenols, are compounds that have the potential to inhibit arginase activity and they may represent an attractive therapeutic option to combat clinical outcomes related to endothelial dysfunction. An extensive review was carried out using all available data published in English in the Pubmed database, and without restriction regarding the year of publication. Despite the increased number of new substances that have been tested as arginase inhibitors, it is rare to find a compound that satisfies all the toxicological criteria to be used in the development of a new drug. On the other hand, recent data have shown that substances from plants have great potential to be applied as arginase inhibitors, most of which are polyphenols. Of the relevant mechanisms in this process, the inhibition of arginase by natural products seems to act against endothelial dysfunction by reestablishing the vascular function and elevating nitric oxide levels (by increasing the amounts of substrate (L-arginine, and endothelial nitric oxide synthase activation and stabilisation) as well as decreasing the generation of reactive species (formed by uncoupledendothelial nitric oxide synthase). This review summarises several topics regarding arginase inhibition by natural substances as well as indicating this pathway as an emergent strategy to elevate nitric oxide levels in disorders involving endothelial dysfunction. In addition, some aspects regarding structural activity and future perspectives are discussed.