6-Gingerol, a major ingredient of ginger, attenuated cisplatin-induced pica in rats via regulating 5-HT3R/Ca2+/CaMKII/ERK1/2 signaling pathway. (January 2023)

• Record Type: Journal Article
• Authors: Mo, Ziyao; Xian, Yihong; Zhang, Ruifang; Dai, Yongzhao; Chen, Weijian; Nie, Ke
• Is Part Of: Journal of functional foods. Volume 100(2023)
• Publication Date: 2023-01
• Subjects: 6-gingerol -- Cisplatin -- Chemotherapy-induced nausea and vomiting -- 5-HT3R -- Ca2+/CaMKII/ERK1/2 signaling; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2022.105389
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: Confirmed the antiemetic effect of 6-gingerol by establishing a rat model of pica. 6-gingerol's antiemetic effect against CINV was related to blocking 5-HT3 receptor. Elucidated the antiemetic mechanisms of 6-gingerol via regulating 5-HT3 R mediated Ca 2+ /CaMKII/ERK1/2 signaling pathway. Abstract: 6-gingerol, the representative single ingredient in ginger, was demonstrated antiemetic properties against CINV via blocking the 5-hydroxytryptamine 3 receptors (5-HT3 Rs), however, its underlying mechanism has not been fully clarified. Emerging evidence suggested that the 5-HT3 R-mediated activation of calcium/calmodulin-dependent protein kinase II/extracellular signal-regulated kinase 1/2 (Ca 2+ /CaMKII/ERK1/2) signaling pathway may contribute to the occurrence of CINV. We first verified the antiemetic action of 6-gingerol via a cisplatin-induced pica model of rats, and found that 6-gingerol significantly reduced the kaolin intake. Further, 6-gingerol markedly down-regulated the expression of 5-HT3 Rs and the levels of calmodulin, CaMKII, p-CaMKII, ERK1/2, p-ERK1/2, and β-arrestin2. Additionally, we demonstrated that 6-gingerol significantly decreased the level of intracellular Ca 2+ in NG108-15 cells, and inhibited the Ca 2+ /CaMKII/ERK1/2 signaling pathway mediated by 5-HT3 Rs. Taken together, 6-gingerol has an antiemetic effect against CINV, and the underlying mechanism may be related to the inhibition of the 5-HT3 R-mediated Ca 2+ /CaMKII/ERK1/2 signaling pathway.