Prokinetic effects of LD02GIFRO on functional gastrointestinal disorder in rats

LD02GIFRO is a novel prokinetic agent formulated with Poncirus fructus and Zanthoxylum sp. fruits. The aim of the present study was to evaluate the effect of LD02GIFRO on delayed gastrointestinal transit (GIT) and colorectal hypersensitivity. To investigate the effect of LD02GIFRO, a rat model of delayed GIT was induced via three mechanisms; postoperative ileus (POI), morphine, and POI plus morphine. Visceromotor responses (VMR) to colorectal distension (CRD) were also evaluated. POI was induced by laparotomy surgery and manipulation of the small intestine under anesthesia, and GIT was calculated by measuring the length that Evans Blue travelled through the gastrointestinal tract in a given time. Oral administration of 260 mg/kg LD02GIFRO caused Evans Blue to migrate significantly further in the delayed GIT models induced by POI, morphine and POI plus morphine compared with the control (P<0.05). This effect was inhibited by atropine, a muscarinic receptor antagonist, and completely abolished by GR125487, a 5-HT₄-receptor antagonist. Furthermore, intraperitoneal administration of 600 and 900 mg/kg LD02GIFRO significantly reduced VMR to CRD in acute and chronic colorectal hypersensitive rat models, induced by acetic acid and trinitrobenzenesulfonic acid, to almost normal levels (P<0.01). In the present study, LD02GIFRO successfully ameliorated delayed GIT models and colorectal hypersensitivity models, suggesting that LD02GIFRO may be an effective therapeutic treatment for patients with functional gastrointestinal disorders and abnormalities in GIT.