Pharmacological basis for the medicinal use of Holarrhena antidysenterica in gut motility disorders

Context: Holarrhena antidysenterica Wall. (Apocynaceae) is widely used in traditional medical system for treatment of constipation, colic, and diarrhea. Aim: This study was carried out to provide pharmacological basis for medicinal use of Holarrhena antidysenterica in gastrointestinal disorders. Materials and methods: Hydro-ethanolic crude extract of Holarrhena antidysenterica (HaCE) and its fractions were studied in various gastrointestinal isolated tissue preparations. Results: In guinea pig ileum tissues, HaCE at 0.3-10mg/mL caused pyrilamine-sensitive spasmogenic effect. When tested in spontaneously contracting rabbit jejunum preparations, HaCE (0.01-3.0mg/mL) caused moderate stimulation, followed by a relaxant effect at next higher concentrations. In presence of pyrilamine, the contractile effect was blocked and the relaxation was observed at lower concentrations (0.01-0.3mg/mL). HaCE inhibited the high K⁺ (80mM)-induced contractions at concentration range of 0.01-1.0mg/mL and shifted Ca⁺⁺ concentration response curves to the right, like that caused by verapamil. Activity-directed fractionation revealed that the spasmogenic component was concentrated in the aqueous fraction, while the spasmolytic component was concentrated in the organic fraction. Discussion and conclusion: These results indicate that the gut stimulant and relaxant activities of Holarrhena antidysenterica are mediated possibly through activation of histamine receptors and Ca⁺⁺ channel blockade, respectively and this study provides sound mechanistic background for its usefulness in gut motility disorders such as constipation, colic, and possibly diarrhea.