Effects of Syzygium aromaticum (L.) Merr. & LM Perry (Cloves) Extract on Uterine Contractions and its Underlying Mechanisms: An Ex vivo Study

Abstract

Abnormal uterine contractility contributes significantly to gynaecological and obstetric disorders such as dysmenorrhea and preterm labour, and current tocolytic therapies are often limited by adverse effects, cost, and inconsistent efficacy. These limitations have stimulated interest in plant-derived agents with smooth muscle relaxant properties. Syzygium aromaticum (clove) is traditionally used for pain and spasms, but its effects on uterine smooth muscle and underlying mechanisms have not been previously reported. In this study, the effects of a hydroethanol extract of Syzygium aromaticum (SAE) was investigated on uterine contractility using isolated uterine strips from non-pregnant Swiss albino mice. Uterine tissues were mounted in organ baths containing aerated physiological solution, and isometric contractions were recorded after equilibration. Cumulative concentrations of SAE (6.25-200 μg/mL) were assessed on spontaneous uterine contractions as well as contractions induced by oxytocin, prostaglandin F2α, potassium chloride, and methacholine. To elucidate the mechanism of action, experiments were conducted in the presence of propranolol and tetraethylammonium, and in the calcium-free medium containing EDTA. Contractile responses were quantified by measuring amplitude, frequency, and area under the curve. SAE produced a concentration-dependent and reversible inhibition on spontaneous uterine contractions, significantly reducing contractile amplitude, frequency, and overall activity. The extract markedly suppressed oxytocin-, prostaglandin F2α-, and methacholine-induced contractions but showed no significant effect on high potassium-induced tonic contractions. In calcium-free conditions, SAE completely abolished oxytocin-induced contractions. The inhibitory effect persisted despite β-adrenergic blockade and potassium channel inhibition. In conclusion, SAE exhibits potent uterine relaxant activity mediated primarily via suppression of receptor-operated signaling and intracellular calcium release, providing pharmacological support for its traditional use in uterine spasmodic disorders.