Gingerol inhibits cisplatin-induced acute and delayed emesis in rats and minks by regulating the central and peripheral 5-HT, SP, and DA systems

Abstract

Gingerol, a biologically active component in ginger, has shown antiemetic properties. Our study aimed to explore the underlying mechanisms of gingerol on protecting rats and minks from chemotherapy-induced nausea and vomiting. The preventive impact of gingerol was evaluated in the pica model of rats and the vomiting model of minks induced by cisplatin at every 6 h continuously for a duration of 72 h. Animals were arbitrarily separated into blank control group, simple gingerol control group, cisplatin control group, cisplatin + metoclopramide group, cisplatin + three different doses gingerol group (low-dose; middle-dose; high-dose). The area postrema as well as ileum damage were assessed using H&E stain. The levels of 5-TH, 5-HT3 receptor, TPH, SERT, SP, NK1 receptor, PPT, NEP, DA, D2R, TH, and DAT were determined using immunohistochemistry or qRT-PCR in rats and minks. All indicators were measured in the area postrema along with ileum. The kaolin intake by rats and the incidence of CINV of minks were significantly decreased after pretreatment with gingerol in a dosage-dependent way for the duration of 0–24-h and 24–72-h. Gingerol markedly decreased the levels of 5-TH, 5-HT3 receptor, TPH, SP, NK1 receptor, PPT, DA, D2R, TH, alleviated area postrema as well as ileum damage, and increased the accumulation of SERT, NEP, DAT in the area postrema along with ileum of rats and minks. Gingerol alleviates cisplatin-induced kaolin intake of rats and emesis of minks possibly by regulating central and peripheral 5-HT system, SP system and DA system. Graphic abstract

<p>[6]-Gingerol Ameliorates Cisplatin-Induced Pica by Regulating the TPH/MAO-A/SERT/5-HT/5-HT₃ Receptor System in Rats</p>

“…14 Gingerol, the main pungent component of ginger, is a mixture of various substances, consisting of [6]-gingerol, [8]-gingerol, [10]-gingerol, [6]-shogaol, etc. 15 Qian et al 13,24,25 and Tian et al 26 reported that gingerol has an activity against cisplatin-induced emesis in mink and cisplatin-induced pica in rats by downregulating 5-HT, dopamine (DA) and substance P (SP) expression and regulating the central and peripheral 5-HT, SP, and DA systems.…”

Ginger relieves intestinal hypersensitivity of diarrhea predominant irritable bowel syndrome by inhibiting proinflammatory reaction

“…Ginger root is the rhizome of the Zingiber officinale Roscoe, which usually contains 1–3% oil. The dosage of ginger is usually standardized according to the curcumin content, which is believed to have antibacterial effects [ 10 ], analgesics [ 11 ], antiemetics [ 12 ] and other physiological effects. In Micromedex (an evidence-based clinical reference tool for hospitals and physicians; www.micromedex.com ) ginger is classified as a broad-spectrum antiemetic drug, which can effectively treat nausea and pregnancy-related vomiting and surgery [ 13 , 14 ].…”

Cannabis, a Miracle Drug with Polyvalent Therapeutic Utility: Preclinical and Clinical-Based Evidence

“…Chemoreceptor trigger zone present in the area postrema allows the chemotactic and other emetic-promoting substances to cross BBB and stimulate the different sections of the DVC [69]. DVC contains various receptors such as D1, D2, 5-HT3, NK1, CB1, and CB2, and these receptors are involved significantly in the induction of emesis [70,71]. Not only CNS but PNS also plays a major role in the etiol- ogy of emesis.…”