Insight into the bronchodilator activity of Vitex negundo

Context: Vitex negundo Linn. (Verbenaceae) is traditionally used in hyperactive respiratory disorders. Objective: This study explored the mechanisms underlying the effectiveness of Vitex negundo in hyperactive respiratory disorders. Materials and methods : Crude extract of V. negundo leaves was obtained. For in vivo bronchodilatory activity in anesthetized rats, different doses (1, 3, 10, 30, and 50 mg/kg) of the crude extract of V. negundo (Vn.Cr) were tested. The underlying mechanisms were studied in isolated guinea pig tracheal strips, suspended in organ baths at 37°C. Results: Intravenous doses of the crude extract of Vn.Cr showed dose-dependent bronchodilatory effect (9-50%) against carbachol (CCh; 100 μg/kg)-induced bronchoconstriction, similar to aminophylline. In isolated guinea-pig tracheal strips, Vn.Crrelaxed CCh (1 μM) and high K+ pre-contractions with respective EC50 values of 0.72 (0.48-1.10; n = 5) and 3.38 mg/mL (1.84-6.21; n = 4), similar to papaverine. Diltiazem also relaxed both contractions with more potency against high K+ pre-contraction (p<0.05). Pre-incubation of the tracheal strips with Vn.Cr potentiated the isoprenaline inhibitory concentration response curves (CRCs), similar to papaverine. Discussion: The inhibitory effect against CCh and high K+ suggests involvement of phosphodiesterase (PDE) inhibitory pathway(s), in addition to an inhibitory effect on Ca++ entry. This finding was further strengthened when pre-treatment of the tracheal strips potentiated the isoprenaline CRCs. Conclusion: Results suggest Vn.Cr possesses a combination of papaverine-like PDE inhibitor and diltiazem-like Ca++ entry blocking constituents, which partly explain its bronchodilatory effect, thus validating its medicinal importance in asthma.