The Traditional Japanese Medicine Rikkunshito Promotes Gastric Emptying via the Antagonistic Action of the 5‐HT₃ Receptor Pathway in Rats

Abstract

The traditional Japanese medicine rikkunshito ameliorates the nitric oxide-associated delay in gastric emptying. Whether rikkunshito affects gastric motility associated with 5-hydroxytryptamine (serotonin: 5-HT) receptors or dopamine receptors is unknown. We examined the effects of rikkunshito on the delay in gastric emptying induced by 5-HT or dopamine using the phenol red method in male Wistar rats. 5-HT (0.01–1.0 mg kg−1, i.p.) dose dependently delayed gastric emptying, similar to the effect of the 5-HT3 receptor agonist 1-(3-chlorophenyl) biguanide (0.01–1.0 mg kg−1, i.p.). Dopamine also dose dependently delayed gastric emptying. The 5-HT3 receptor antagonist ondansetron (0.04–4.0 mg kg−1) and rikkunshito (125–500 mg kg−1) significantly suppressed the delay in gastric emptying caused by 5-HT or 1-(3-chlorophenyl) biguanide. Hesperidin (the most active ingredient in rikkunshito) suppressed the 5-HT-induced delayed gastric emptying in a dose-dependent manner, the maximum effect of which was similar to that of ondansetron (0.4 mg kg−1). The improvement obtained by rikkunshito or ondansetron in delaying gastric emptying was completely blocked by pretreatment with atropine. Rikkunshito appears to improve delay in gastric emptying via the antagonistic action of the 5-HT3 receptor pathway.

Rikkunshito, a Kampo Medicine, Ameliorates Post-operative Ileus by Anti-inflammatory Action

“…These findings might indicate the possibility that RKT clinically ameliorates POI through improvements in both Until now, several mechanisms for the gastroprokinetic action of RKT have been reported. RKT increases gastric emptying by the 5-HT 3 receptor antagonism in rats (2). Efficacy of RKT was reported to be comparable to the 5-HT 3 antagonist ondansetron.…”

“…These flavonoids also induce prokinetic ability through improvement of ghrelin release owing to the 5-HT 2B and 5-HT 2C receptor antagonistic action (3). Moreover it was demonstrated that hesperidin showed pharmacological efficacy in enhancing gastric motility via antagonism of a 5-HT 3 receptor-associated pathway (2). These flavonoids and herbs may have multiple actions including anti-inflammatory ability.…”

“…RKT promotes delayed gastric emptying through antagonistic action against the 5-HT 3 receptor (2). RKT is also known as a prescription to increase appetite, and its action mechanisms were mediated from inhibition of 5-HT 2B and 5-HT 2C receptors (3).…”

New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line

“…Additionally, increasing evidence from experimental animal models has shown that rikkunshito ameliorates several types of anorexia (23,24,57). It has been reported that with rikkushito there is an increase in the secretion of the orexigenic hormone ghrelin by the inhibition of 5-HT2B/2C receptors, an enhancement of ghrelin receptor (GHSR) signaling efficiency, and a facilitation of gastric emptying and gastric adaptive relaxation, all of which may contribute to ameliorate anorexia (24,32,57,60,64). Herein, we examined specifically the efficacy of rikkunshito in ameliorating anorexia symptoms in our novel cancer cachexia rat models.…”

Effect of rikkunshito, a Japanese herbal medicine, on gastrointestinal symptoms and ghrelin levels in gastric cancer patients after gastrectomy

“…Rikkunshito, which was obtained from Tsumura (Tokyo, Japan), has 8 main constituents: Glycyrrhizae radix (4.7 %), Zingiberis rhizoma (2.3 %), Atractylodis lanceae rhizoma (18.6 %), Zizyphi fructus (9.3 %), Aurantii nobilis pericarpium (9.3 %), Ginseng radix (18.6 %), Pinelliae tuber (18.6 %), and Hoelen (18.6 %). More detailed descriptions of all the substances that are known to be included in rikkunshito are found in a previous report [26]. Patients who had undergone gastrectomy invariably received 2.5 g of rikkunshito before each meal (7.5 g/day) for 4 weeks.…”