Hydro-alcoholic extract of Matricaria recutita exhibited dual anti-spasmodic effect via modulation of Ca2+ channels, NO and PKA2-kinase pathway in rabbit jejunum

Abstract

Objective: Several studies have shown the antispasmodic activity of Matricariarecutita without detailing the underlying mechanism(s). The present study was designed to determine whether the antispasmodic mechanisms of M. recutita extract mediated via histaminergic/cholinergic receptors, Ca²⁺channels, activation of PKA₂and NO release in isolated rabbit jejunum.<br /> Methods and Materials: The concentration- dependent (3 × 10^-3–1.3 × 10^-2 mg/ml) antispasmodic effect of the hydro-alcoholic extract of M. recutita flowers was studied in isolated rabbit jejunum. The isolated jejunum preparations were divided into seven groups, including the pharmacological probes that modulate cholinergic, histaminergic, and nitrergic receptors, as well as PKA₂. <br /> Results: M. recutita inhibited spontaneous smooth muscle contractility of the jejunum in a concentration-dependent manner (3 × 10^-3–1.3 × 10^-2mg/ml) and reduced both K⁺- and Ca²⁺-induced contractions, which is similar to the effect of verapamil. The antispasmodic effect of M. recutita wasinhibited by H89 (a PKA₂inhibitor). The myorelaxant effect of M. recutita increased in the presence of ACh/His and H89. <br /> Conclusion: M. recutita evoked antispasmodic and spasmolytic effects mediated through different signaling pathways. Our results have shown this dual inhibitory effect is mediated by blocking Ca²⁺ channels, activating His and ACh receptors, releasing NO, and activating PKA₂.