| dc.description | Previous studies have described the antispasmodic effect of mangiferin, a natural glucoside xanthone (2-C-b-Dglucopyranosyl-1,3,6,7-tetrahydroxyxanthone)
that is present in mango trees and other plants, but its mechanism of action
remains unknown. The aim of this study was to examine the potential contribution of the nitric oxide-cyclic GMP pathway
to the antispasmodic effect of mangiferin on isolated tracheal rings preparations. The functional effect of mangiferin on
allergic and non-allergic contraction of guinea pig tracheal rings was assessed in conventional organ baths. Cultured
tracheal rings were exposed to mangiferin or vehicle, and nitric oxide synthase (NOS) 3 and cyclic GMP (cGMP) levels were
quantified using western blotting and enzyme immunoassays, respectively. Mangiferin (0.1–10 mM) inhibited tracheal
contractions induced by distinct stimuli, such as allergen, histamine, 5-hydroxytryptamine or carbachol, in a concentrationdependent
manner. Mangiferin also caused marked relaxation of tracheal rings that were precontracted by carbachol,
suggesting that it has both anti-contraction and relaxant properties that are prevented by removing the epithelium. The
effect of mangiferin was inhibited by the nitric oxide synthase inhibitor, Nv-nitro-L-arginine methyl ester (L-NAME)
(100 mM), and the soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 mM), but not
the adenylate cyclase inhibitor, 9-(tetrahydro-2-furyl)adenine (SQ22536) (100 mM). The antispasmodic effect of mangiferin
was also sensitive to K+ channel blockers, such as tetraethylammonium (TEA), glibenclamide and apamin. Furthermore,
mangiferin inhibited Ca2+
-induced contractions in K+ (60 mM)-depolarised tracheal rings preparations. In addition,
mangiferin increased NOS3 protein levels and cGMP intracellular levels in cultured tracheal rings. Finally, mangiferininduced
increase in cGMP levels was abrogated by co-incubation with either ODQ or L-NAME. These data suggest that the
antispasmodic effect of mangiferin is mediated by epithelium-nitric oxide- and cGMP-dependent mechanisms. | |
