Ghrelin receptor is activated by naringin and naringenin, constituents of a prokinetic agent Poncirus fructus

Abstract

Ethnopharmacological relevance: Poncirus fructus (PF), also known as a dried immature fruit of Poncirus trifoliata (L) Raf. (Rutaceae), has long been traditionally used for the various gastrointestinal disorders in Eastern Asia. Aim of study: The aqueous extract of PF (PF-W) has the strong prokinetic effect, yet the underlying mechanism is still elusive. The present study investigated whether PF-W has any effect on motilin receptor or ghrelin receptor, since these receptors enhance intestinal motility when activated. Materials and methods: The effect of PF-W and its components on motilin or ghrelin receptor was determined by calcium imaging and whole-cell patch clamp methods. Results: PF-W activates the ghrelin receptor, but not the motilin receptor, resulting in a transient increase of intracellular calcium levels. Furthermore, among various constituents of PF, only naringin and naringenin evoked the intracellular calcium augmentation via the ghrelin receptor. Moreover, cortistatin-8 - a ghrelin receptor inhibitor - specifically blocked naringin- and naringenin-induced calcium increases. In addition, naringin and naringenin induced inward currents in ghrelin receptor-expressing cells under whole-cell patch clamp configuration. Conclusion: PF-W activates the ghrelin receptor, and naringin and naringenin are key constituents responsible for the activation of ghrelin receptor. Therefore, the present study suggests that the ghrelin receptor is a molecular entity responsible for the strong prokinetic activity of PF-W. (C) 2013 Elsevier Ireland Ltd. All rights reserved.