Inhibition of carbachol-induced gastrointestinal motility mediates the antidiarrheal activity of <i>Combretum platypetalum</i> (Welw.) Hutch & Dalziel leaf extract

Purpose: To evaluate the mechanism of antidiarrheal activity of the leaves of Combretum platypetalum (Welw.) Hutch & Dalziel (Combretaceae) in Swiss albino mice. Methods: The study employed bioactivity-guided fractionation of the extract, which was separated using hexane, ethyl acetate, and butanol. Further fractionation was done with vacuum liquid chromatography (VLC). The antidiarrheal activity of the extracts (100 - 400 mg/kg) and fractions (100 - 200 mg/kg) was evaluated using the charcoal meal antimotility and castor oil-induced antisecretory activity models with 3 mg/kg loperamide standard. The antimotility mechanism of the most active VLC fraction was assessed by measuring gastrointestinal transit (GT) and gastric emptying (GE). Results: Maximum antimotility effect was achieved at 400 mg/kg extract (70.14 %), surpassing loperamide (61.88 %; p < 0.01). In the GT test, the control group's charcoal meal traversed a long distance (peristaltic index, PI: 91.48 %), which was significantly reduced (p < 0.001) with ethyl acetate fraction treatment at 50, 100, and 200 mg/kg, showing PIs of 23.46 %, 20.18 and 51.74 %, respectively. GT significantly increased (p < 0.05) with carbachol and serotonin (10 mg/kg) and 30 mg/kg metoclopramide by 83.5, 69.1 and 68.9 %, respectively, compared to control animals (44.3 ± 5.5 %). Pre-treatment with VLC fraction (200 mg/kg) significantly (p < 0.05) inhibited carbachol's action on GE (75.6 vs 27.6 %) but had no significant impact on metoclopramide and serotonin's actions on GE. Conclusion: Combretum platypetalum's antidiarrheal activity is mediated by an antimotility mechanism, specifically through the inhibition of carbachol-induced GT and GE.