Correction: Mangiferin Prevents Guinea Pig Tracheal Contraction via Activation of the Nitric Oxide-Cyclic GMP Pathway

Abstract

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 Ca 2+ -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.