Antihypertensive activity of flowering twigs of Calotropis procera (Ait.) is predominantly mediated through vasorelaxant pathway

Objective: To evaluate the crude methanolic (Cp.Cr) and aqueous (Cp.Aq) extracts of Calotropis procera Aiton for acute toxicity and antihypertensive effects, validating its ethnomedicinal use in cardiovascular disorders. Methods: Phytochemical screening was conducted to determine the chemical constituents of C. procera. Acute toxicity was assessed in BALB/C mice using oral doses of 10, 100, 1000, 1500, and 2000 mg/kg. Vasorelaxant effects were evaluated using rabbit aortic strips pre-contracted with 1 µM norepinephrine and 80 mM potassium chloride (high K⁺) to explore the mechanism of action. Antihypertensive activity was assessed in hypertensive Sprague-Dawley rats at doses of 1 and 10 mg/kg orally, using the tail-cuff method to measure systolic blood pressure. Results: Phytochemical analysis revealed the presence of flavonoids, saponins, cardiac glycosides, and terpenoids. The extract was non-toxic up to 1500 mg/kg, while a 75% mortality rate was observed at 2000 mg/kg. Both Cp.Cr and Cp.Aq induced dose-dependent relaxation in K⁺ and norepinephrine-induced contractions. The EC₅₀ for Cp.Aq was 0.15 mg/ml for KCl-induced and 0.13 mg/ml for NE-induced contractions. A significant reduction in systolic blood pressure (p<0.05) was observed, particularly with the aqueous fraction of C. procera. Conclusion: The flowering twigs of C. procera exhibit significant antihypertensive effects, likely mediated through vasorelaxation via inhibition of voltage-gated calcium channels. These findings support its potential use in hypertension management and provide evidence of its safety and pharmacological efficacy.