Hydro-alcoholic extract of Matricaria recutita exhibited dual anti-spasmodic effect via modulation of Ca(2+) channels, NO and PKA(2)-kinase pathway in rabbit jejunum

OBJECTIVE: Several studies have shown the antispasmodic activity of Matricaria recutita 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, Ca(2+)channels, activation of PKA(2 )and NO release in isolated rabbit jejunum. MATERIALS AND METHODS: 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 PKA(2). RESULTS: M. recutita inhibited spontaneous smooth muscle contractility of the jejunum in a concentration-dependent manner (3 × 10(-3)–1.3 × 10(-2 )mg/ml) and reduced both K(+)- and Ca(2+)-induced contractions, which is similar to the effect of verapamil. The antispasmodic effect of M. recutita was inhibited by H89 (a PKA(2 )inhibitor). The myorelaxant effect of M. recutita increased in the presence of ACh/His and H89. 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 Ca(2+) channels, activating His and ACh receptors, releasing NO, and activating PKA(2).