Assessment of In Vitro Airway Smooth Muscle Relaxant Activity of Rhus coriaria L. Fruit Ethanolic Extract and Its Possible Mechanisms

Abstract

Rhus coriaria L. (Anacardiaceae), also known as Sumac, is commonly used as a spice, flavoring agent, and as a traditional medicinal herb. This includes also the traditional use for treating asthma, catarrh, and common colds. The accumulating evidence supports its cardioprotective, antidiabetic, neuroprotective, anticancer, gastroprotective, antibacterial, anti-inflammatory, antiviral, antioxidant, and respiratory effects. However, there are no previous studies that have shown its effects and mechanism in the airway smooth muscle tone, and therefore, the aim of our study was to investigate the in vitro pharmacological action of R. coriaria L. extract (RCE) on the rat isolated tracheal and bronchial preparations by exploring its relaxant activity and mechanism of action. The direct relaxant effect of RCE (0.1–0.7 mg/mL) was tested in the rat bronchi and trachea rings precontracted by carbachol (CCh). In addition, the pretreatment with RCE (1 mg/mL) was tested on the bronchial and tracheal reactivity induced by CCh, potassium chloride (KCl), or CaCl₂. In addition, the cyclooxygenase inhibitor indomethacin and the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME), respectively, were used for exploring the mechanisms of RCE-induced relaxation and reduction of reactivity. Our findings demonstrated that RCE induced a concentration-dependent relaxation and a significant reduction of reactivity, significantly reduced with either indomethacin or L-NAME. In addition, RCE decreased the responsiveness to KCl and affected the extracellular Ca²⁺-induced contraction in the tissues with added CCh or KCl in Ca²⁺-free Krebs–Henseleit solution. In summary, we have shown that RCE displayed relaxant activities in the in vitro airway smooth muscles, and the possible mechanisms seems to involve the prostaglandin, nitric oxide, and Ca²⁺ pathways. Taken together, our findings indicate the potential role of RCE in the treatment of respiratory diseases with limited airflow, or obstructive respiratory diseases, and could justify its traditional use in the respiratory diseases.