Vasorelaxant and Antihypertensive Effects of Extracts from the Leaves of Casimiroa edulis La Llave (Rutaceae) by NO Release and Calcium Channel Blockade.

Abstract

Background: Casimiroa edulis La Llave (Rutaceae), commonly known as "zapote blanco", is a tree widely distributed in the tropical and subtropical areas of Mexico. The decoction of its leaves is traditionally used as a natural remedy to treat hypertension and anxiety.

Objective: The present study aimed to determine the vasorelaxant and antihypertensive effects of C. edulis extracts and evaluate the acute and sub-acute toxicity of one of the most active extracts.

Methods: The hydro-alcohol and organic (hexane, dichloromethane, and methanol) extracts, obtained from the leaves of C. edulis, were evaluated on isolated aorta rat rings in the presence and absence of endothelium to determine their vasorelaxant effect. Then, most active extracts were studied to evaluate the functional mechanism of their vasorelaxant action and antihypertensive effect on spontaneously hypertensive rats (SHR). The acute and sub-acute toxicity of dichloromethane extract was evaluated following the OECD 423 and 407 protocols.

Results: The hexane (HE) and dichloromethane (DE) extracts from Casimiroa edulis induced significant vasorelaxant action on isolated rat aortic rings with (Emax 104.7 ± 1.4% and Emax 97.3 ± 6.7%, respectively) and without (Emax 94.9 ± 3.5% and Emax 67.4 ± 1.0%, respectively) endothelium, and this effect was partially endothelium-dependent. Their vasorelaxant action was modified by L-NAME (nitric oxide synthase inhibitor) and ODQ (soluble guanylyl cyclase inhibitor); however, indomethacin did not modify the effect. Also, both HE and DE significantly decreased the contraction induced by KCl in a concentration-dependent manner and the maximal effect induced by CaCl2. Moreover, DE showed a significant decrease in systolic and diastolic blood pressure in SHR at 7 hours and 15 days after treatment, respectively. Finally, the toxicity test of DE allowed classifying it in category 5, indicating it to be a non-toxic extract based on OECD guideline 423; the LD50 value was estimated to be greater than 2,000 mg/Kg and smaller than 5,000 mg/Kg in Wistar rats.

Conclusion: The results demonstrated hexane and dichloromethane extracts to exert a vasorelaxant effect through endothelium-dependent NO release and cGMP increase, as well as by calcium channel blockade. Also, dichloromethane extract showed efficacy and security as a potential antihypertensive agent.