Prokinetic effects of Citrus reticulata and Citrus aurantium extract with/without Bupleurum chinense using multistress-induced delayed gastric emptying models

Abstract

Context

Citrus aurantium L (Rutaceae) (Au) and Citrus reticulata Blanco (Rutaceae) (Ci) are commonly used as couplet prokinetics and Bupleurum chinense DC. (Umbelliferae) (Bup) is an herbal antidepressant in traditional Chinese medicine.

Objective

This study evaluates the synergistic prokinetic effects of Bup with Au and Ci in mice suffering from multistress-induced delayed gastric emptying (DGE).

Materials and methods

Kunming mice were divided into four groups: control, DGE, AuCi and AuCiBup. Mice were gavaged with AuCi (14.25 g/kg) or AuCiBup (22.13 g/kg) extract for 12 days. Gastric reminder rate, intestinal driving ratio, sucrose preference and open field test were examined, and serotonin (5-HT), motilin (MTL), substance P (SP), 5-HT ₄R and c-kit were assayed. Intracellular Ca ²⁺ levels in primary cultured gastric smooth muscle cells (GSMCs) were determined.

Results

Both AuCi and AuCiBup treatment significantly reduced gastric residual rate (39.5% and 67.7%, p < 0.01). Higher serum levels of 5-HT, MTL and SP were observed in treatment groups (AuCi: 0.060 mg/L, AuCiBup: 0.089 mg/L, DGE: 0.025 mg/L, p < 0.01). The expression of 5-HT ₄R and c-kit in the antrum and duodenum was upregulated after treatment (AuCi and AuCiBup, 4.3-times, 2.8-times to DGE, p < 0.01). Medicated serums of AuCi and AuCiBup effectively increased the influx of Ca ²⁺ into GSMCs in vitro (1.8-times, p < 0.01). In terms of 5-HT ₄R expression, circulatory contents of 5-HT and SP and Ca ²⁺ influx, AuCiBup demonstrated better prokinetic effects than AuCi.

Conclusions

These findings indicate the potential for developing combination therapy with antidepressants and prokinetics in gastrointestinal dysmotility management.