Identification of G protein-coupled receptor 55 (GPR55) as a target of curcumin

Naoki Harada,Hiroko Horiuchi,Claus Schneider,Norio Yamamoto,Takashi Iuni,Yoshiaki Teraoka,Shigenobu Matsumura,Yoh Shinmori,Paula B Luis,Akil I Joseph,Mai Okuyama,Tomoya Kitakaze,Naoki Goshima,Ryoichi Yamaji,Yumi Arahori,Hiroshi Inui,Tohru Hira

doi:10.1038/s41538-021-00119-x

Abstract

The identification of molecular targets of bioactive food components is important to understand the mechanistic aspect of their physiological functions. Here, we have developed a screening system that enables us to determine the activation of G protein-coupled receptors (GPCRs) by food components and have identified GPR55 as a target for curcumin. Curcumin activated GPR55 and induced serum-response element- and serum-response factor-mediated transcription, which were inhibited by Rho kinase and GPR55 antagonists. Both the methoxy group and the heptadienone moiety of curcumin were required for GPR55 activation. The F1905.47 residue of GPR55 was important for the interaction with curcumin. The curcumin-induced secretion of glucagon-like peptide-1 in GLUTag cells was inhibited by a GPR55 antagonist. These results indicate that expression screening is a useful system to identify GPCRs as targets of food components and strongly suggest that curcumin activates GPR55 as an agonist, which is involved in the physiological function of curcumin.

Highlights

Curcumin is the predominant bioactive curcuminoid in turmeric (Curcuma longa), which is widely used as a spice for preparing curry
HEK293FT cells were transfected with G protein-coupled receptors (GPCRs) expression vectors and a p4xCRE-3xSRE-TATALuc2P reporter vector followed by stimulation with curcumin
After screening 258 human GPCRs, we identified G protein-coupled receptor 55 (GPR55) as a

Summary

Introduction

Curcumin is the predominant bioactive curcuminoid in turmeric (Curcuma longa), which is widely used as a spice for preparing curry. Curcumin is absorbed by the body and is partly metabolized to tetrahydrocurcumin, ferulic acid, and vanillin[1]. Tetrahydrocurcumin, a major metabolite of curcumin, can be produced by the gut microbiota[2]. Curcumin coexists as the diketo and keto-enol tautomers in solution[3]. Various activities of curcumin, such as anti-diabetic, anti-oxidative, antitumorigenic, anti-inflammatory, and neurotrophic properties, have been widely investigated[4,5,6]. The anti-diabetic property of curcumin is due to the induction of glucagon-like peptide-1 (GLP-1) secretion in intestinal L-cells[7,8,9]. The molecular mechanisms by which curcumin exerts its biological effects have not yet been fully elucidated. G protein-coupled receptors (GPCRs) are seven-transmembrane receptors that form the largest family of cell-surface receptors

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Conclusion