Laboratorio de Investigación Integral Cardiometabólica, Instituto Politécnico Nacional, Ciudad de Mexico 11340, Mexico.
School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Int J Mol Sci. 2022 Aug 11;23(16):8962. doi: 10.3390/ijms23168962.
(-)-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.
(-)-表儿茶素（EC）是一类被称为类黄酮的生物分子大家族的一部分，广泛分布于植物界。多项研究表明 EC 消费具有有益作用。这些报道的许多作用是通过激活与两种特定受体的激活相关的信号通路来发挥的：G 蛋白偶联雌激素受体（GPER），一种跨膜受体，和孕烷 X 受体（PXR），它是一种核受体。然而，EC 的作用非常多样化，这两个受体不能描述完整的现象。阿立新受体或 APLNR 被归类于 G 蛋白偶联受体（GPCR）家族，能够激活 G 蛋白经典途径和β-arrestin 转导器，参与受体脱敏和内化现象。β-arrestin 在选择性药理学和所谓的“偏向激动剂”的介质中引起了关注。通过分子动力学（MD）和体外测定，我们证明了 EC 如何通过充当偏向激动剂来募集 APLN 受体的β-arrestin 处于活性构象。
