Gut modulatory effects of Daphne oleoides are mediated through cholinergic and Ca ⁺⁺ antagonist mechanisms

Context: The present study describes the spasmogenic and spasmolytic activities of Daphne oleoides Schreb. (Thymelaeaceae), exploring the possible underlying pharmacological mechanisms. Aim: Pharmacological investigation of Daphne oleoides to provide evidence for its therapeutic application in gastrointestinal motility disorders. Materials and methods: Methanol crude extract of Daphne oleoides (Do.Cr) was studied in gastrointestinal isolated tissues. Results: In spontaneously contracting rabbit jejunum preparations, Do.Cr at 0.3-3.0 mg/mL caused moderate stimulation, followed by relaxant effect at the next higher concentrations (5.0-10 mg/mL). In presence of atropine, spasmogenic effect was blocked and the relaxation was emerged, suggesting that the spasmogenic effect of Daphne oleoides is mediated through activation of muscarinic receptors. When tested against the high K ⁺ (80 mM)-induced contractions, Do.Cr (0.3-5.0 mg/mL), like verapamil, inhibited the induced contractions, suggesting Ca ⁺⁺ channel blockade (CCB) effect. The CCB effect was further confirmed when pre-treatment of the tissue with Do.Cr shifted the Ca ⁺⁺ concentration-response curves to the right, similar to that caused by verapamil. Discussion and conclusion: These results indicate that Daphne oleoides exhibits gut excitatory and inhibitory effects, occurred via cholinergic and Ca ⁺⁺ antagonistic pathways, respectively.