Pharmacological basis for medicinal use of Ziziphyus nummularia (Rhamnaceae) leaves in gastrointestinal disorders

Purpose: To explore the pharmacological basis for the folkloric use of Ziziphus nummularia for treating diarrhea and gastrointestinal spasm. Methods: Ziziphus nummularia crude extract (Zn.Cr) was investigated for antidiarrheal activity (50, 100 and 300 mg/kg) in terms of reduction diarrhea droppings as well as for antisecretory activity (300 and 1000 mg/kg) in castor-oil induced model in mice. The effect of the extract on potassium chloride (KCl, 80 mM)-induced contractions in isolated rabbit jejunum tissues were was also examined. Furthermore, the antiulcer properties of the extract was assessed in an ethanol-induced gastrointestinal ulcer model. Results: Zn.Cr (50 – 1000 mg/kg) exhibited protective effect against castor oil-induced diarrhea (p < 0.05, p < 0.01 vs saline group) and intestinal fluid accumulation (p < 0.001 vs. castor oil group) in mice. In isolated rabbit jejunum model, Zn.Cr concentration-dependently (0.01, 0.1, 0.3, 0.5, 1 and 3 mg/mL) caused relaxation of spontaneous and KCl-induced contractions, similar to verapamil. Calcium antagonistic effect was indicated, as pretreatment of intestinal tissues with Zn.Cr (0.3, 0.5 and 1.0 mg/mL) produced a rightward shift in Ca²⁺ concentration-response curves, with suppression of maximum contraction. In ethanol-induced gastric ulceration assay, Zn.Cr (300 and 1000 mg/kg) caused 52.5 and 93.6 % inhibition, respectively (p < 0.001 vs. saline group). Conclusion: These results reveal that Ziziphus nummularia possesses anti-diarrheal, anti-secretory, anti-spasmodic and anti-ulcer actions, mediated possibly through voltage-gated Ca2+channel blockade.