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.
['Khan|Munasib|M|', 'Shah|Abdul Jabbar|AJ|', 'Gilani|Anwarul Hassan|AH|']
D000818:Animals D016084:Bronchoconstriction D001993:Bronchodilator Agents D004305:Dose-Response Relationship, Drug D005260:Female D006168:Guinea Pigs D008297:Male D009924:Organ Culture Techniques D010936:Plant Extracts D018515:Plant Leaves D051381:Rats D017207:Rats, Sprague-Dawley D014132:Trachea D020950:Vitex
crude extract Aminophylline papaverine diltiazem asthma PDE inhibition bronchodilatation carbachol bronchoconstriction guinea pig trachea