Gastrouterine Smooth Muscle Tone Modulatory Action of Neem Fruit Extract is Mediated via Muscarinic Receptors and Ca2+ Channels

Introduction: Neem (scientific name Azadirachta indica A. Juss) is a popular medicinal plant in South Asia. We show here the smooth muscle stimulant and relaxant properties of the neem fruit extract. Materials and Methods: Neem fruit were soaked in 70% aqueous-methanol, then dried to obtain a thick brown extract (Ai.Cr). Different isolated gastrointestinal and uterine tissue preparations were obtained and were maintained in tissue baths with a physiological salt solution. Results: The extract exhibited a stimulant effect in increasing concentrations (0.03 to 3.0 mg/ml) in isolated rabbit jejunum. When this activity of the extract was challenged with a ganglion blocker hexamethonium, it was not blocked. It was completely antagonized when challenged with atropine, a cholinergic blocker. Once the spasmogenic effect was blocked, Ai.Cr exhibited a spasmolytic effect (1-10 mg/ml). Ai.Cr was also able to suppress K+ (80 mM) sustained contractions in jejunum in increasing concentrations (0.03-3 mg/ml), indicating calcium channel blockade (CCB). Likewise, Ai.Cr exhibited an atropine-sensitive stimulant response (0.03-5 mg/ml) followed by a CCB-type relaxant effect (0.3-3 mg/ ml) in stomach fundus and ileum preparations of rat. In rat uterus, the crude extract in increasing concentrations (0.1-10 mg/ml), exhibited uterotonic activity that was partially sensitive to atropine. This indicated that there is an additional stimulant component(s) active in uterine tissues. Conclusion: These results show a combination of spasmogenic and spasmolytic effects of Ai.Cr on smooth muscles from rabbits and rats mediated possibly via muscarinic and CCB mechanisms.