Isolation and chemical and pharmacological characterization of potential trace amine-associated receptor antagonist from plant sources

• Main Author: Natividad, Gaudencio M.
• Published: Cardiff University 2010
• Subjects: 615.321
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.584891

The present study describes the preliminary evaluation of Philippine medicinal plants <italic>Artemisia vulgaris, Chrysanthemum coronarium, Moringa oleifera, Sesbania grandiflora</italic> and <italic>Vitex negundo</italic> for their antagonistic activity at selected biogenic amine receptors on smooth muscle of the airways, gastrointestinal tract and vascular system. The antagonistic activity of these plants were studied against dose-response curves for contractions of the guinea pig ileum, trachea and aorta to 5-hydroxytryptamine (5-HT2 receptors), methacholine (M3 muscarinic receptors), histamine (Hi receptors), phenylephrine (d -adrenoceptors) and P-phenylethylamine (trace amine-associated receptors, TAARi). The methanolic extracts of <italic>S. grandiflora</italic> (flowers and leaves) revealed the presence of histamine Hi receptor and muscarinic M3 receptor antagonist in the ileum. The <italic>A. vulgaris</italic> chloroform (AV-CHC13) and methanol (AV-MeOH) extracts, and the acid-base extract of <italic> V. negundo</italic> (VN-E) showed histamine Hi antagonism in the ileum and trachea. Further analysis of AV-CHCI3 isolated two major components yomogin and l,2,3,4-diepoxy-ll(13)-eudesmen-12,8-olide. Yomogin a sesquiterpene lactone exhibited a novel histamine Hi receptor antagonism in the ileum. Repeated exposure of aortic rings to phenylephrine and (3-PEA CRCs produced significant increases in maximum vascular tension due to enhanced intracellular Ca2+ mobilization. Both the AV-CHCI3 and VN-E inhibited this enhanced response. Further analysis of AV-CHCI3 revealed that it is probably inhibiting the increase of vascular tone mediated via intracellular Ca2+ release regulated by ryanodine. This study further validates the traditional use of <italic>S. grandiflora, A. vulgaris</italic> and <italic>V. negundo</italic> in the treatment of hyperactive gut, asthma and hypertension.