Waltheria indica L. (Malvaceae) has been recognized in traditional medicine for various therapeutic effects, including anti-inflammatory, antioxidant, anticancer and bronchorelaxant activities. This study aimed to investigate the relaxant effects of Waltheria indica extracts on rat tracheal smooth muscle and to explore the involvement of ?2-adrenergic and muscarinic receptors, calcium and potassium channels, nitric oxide (NO), and the cyclooxygenase pathway in this response. Tracheal rings were contracted with KCl (80 mM) or acetylcholine (10 ?M), and cumulative concentrations of W. indica extract (10, 30, 100, 300, 1000,2000 and 3000 µg/ml) were added to the organ bath at 15 min intervals. Isoprenaline (10, 30, 100, 300, 1000, 2000 and 3000 µg/ml) was used as a positive control in unincubated tissue. The relaxant effects of W. indica extracts were assessed in unincubated tissues and tissues incubated with propranolol, atropine, glibenclamide, indomethacin, tetraethylammonium (TEA), methylene blue and N (gamma)-nitro-L-arginine methyl ester (L-NAME). W. indica showed a concentration-dependent relaxant effect on unincubated isolated tracheal rings contracted by KCl (80 mM) or acetylcholine (10 ?M) (P < 0.01 to p < 0.001). There was no significant difference in the relaxant effects of W. indica between the tissues unincubated and those incubated with glibenclamide, TEA, indomethacin, and L-NAME. The relaxant effects were significantly weaker in tissues incubated with methylene blue and atropine than in unincubated tissues. The relaxant effects of different concentrations of W. indica extract were not significantly different from those of isoprenaline. W. indica extracts showed potent relaxing effects on isolated rat tracheal rings. The results suggest that stimulation of soluble guanylate cyclase and/or blockade of muscarinic receptors may be plausible mechanisms underlying the plant's relaxing effects.

Keywords: GMPc release; Muscarinic receptor; Waltheria indica; Smooth muscle; Soluble guanylate cyclase