(-)-Epicatechin Is a Biased Ligand of Apelin Receptor

Abstract

(-)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids and is widely distributed in the plant kingdom. Several studies have shown the beneficial effects of EC consumption. Many of these reported effects are exerted by activating the signaling pathways associated with the activation of two specific receptors: the G protein-coupled estrogen receptor (GPER), a transmembrane receptor, and the pregnane X receptor (PXR), which is a nuclear receptor. However, the effects of EC are so diverse that these two receptors cannot describe the complete phenomenon. The apelin receptor or APLNR is classified within the G protein-coupled receptor (GPCR) family, and is capable of activating the G protein canonical pathways and the β-arrestin transducer, which participates in the phenomenon of receptor desensitization and internalization. β-arrestin gained interest in selective pharmacology and mediators of the so-called “biased agonism”. With molecular dynamics (MD) and in vitro assays, we demonstrate how EC can recruit the β-arrestin in the active conformation of the APLN receptor acting as a biased agonist.

Chronic Effects of Apelin on Cardiovascular Regulation and Angiotensin II-Induced Hypertension

“…Therefore, it is crucial to design APJ receptor biased agonists in order to stimulate the APJ-mediated signaling pathways selectively: G protein-dependent versus β-arrestin recruitment-dependent. Research on APJ receptor biased agonists is under intense investigation currently [17][18][19][20]. To examine this hypothesis, our research group is currently designing and evaluating the efficacy of novel APJ receptor biased agonists [18].…”