Inhibitory Effect of the Norlignan 2-(2′-Hydroxy-4′,6′-dimethoxyphenyl)-5-[(E)-propenyl]benzofuran from Krameria tomentosa on Acetylcholine-Induced Relaxation of the Rat Aorta

Abstract

In this work, we studied the effect of the norlignan 2-(2′-hydroxy-4′,6′-dimethoxyphenyl)-5-[(E)-propenyl]benzofuran (DMPP) in the rat aorta. In aortic rings with intact endothelium, DMPP inhibited in a concentration-dependent manner the vasodilator effect produced by acetylcholine with an IC₅₀ value of 31.2 ± 6.3 μM. DMPP also inhibited basal nitric oxide production. In endothelium-denuded vessels DMPP was without effect whereas superoxide dismutase (SOD) was effective in potentiating responses to the NO donor SIN-1. Contractile effects of carbachol in guinea-pig ileum and trachea were unaffected by DMPP. It is concluded that DMPP inhibits the endothelium-dependent relaxation induced by acetylcholine in the rat aorta without affecting receptor or smooth muscle cells function. Decreased nitric oxide production by endothelial cells seems to be the mechanism involved in the inhibitory effect of DMPP.

References

• 1 Silva S AS, Castro J CM, Silva T G, Cunha E VL, Barbosa-Filho J M, Silva M S. Kramentosan, a new trinorlignan from the roots of Krameria tomentosa .  Nat Prod Lett. 2001;  15 323-9
• 2 Achenbach H, Gross J, Dominguez X A, Cano G, Star J V, Brussolo L DC. et al . Lignans, neolignans and norneolignans from Krameria cystisoides .  Phytochemistry. 1987;  26 1159-66
• 3 Achenbach H, Utz W, Usubillaga A, Rodriguez H A. Studies on Krameriaceae. 7. Lignans from Krameria ixina .  Phytochemistry. 1991;  30 3753-7
• 4 Achenbach H, Utz W, Sanchez H V, Touche E MG, Verde J S, Dominguez X A. Neolignans, nor-neolignans and other compounds from roots of Krameria grayi .  Phytochemistry. 1995;  39 413-5
• 5 Son H J, Lee H J, Yun-Choi S H, Ryu J H. Inhibitors of nitric oxide synthesis and TNF-alpha expression from Magnolia obovata in activated macrophages.  Planta Med. 2000;  66 469-71
• 6 Taniguichi C, Homma M, Takano O, Hirano T, Oka K, Aoyagi Y. et al . Pharmacological effects of urinary products obtained after treatment with saiboku-to, a herbal medicine for bronchial asthma, on type IV allergic reaction.  Planta Med. 2000;  66 607-11
• 7 Lee A K, Sung S H, Kim Y C, Kim S G. Inhibition of lipopolysaccharide-inducible nitric oxide synthase, TNF-α and COX-2 expression by sauchinone effects on I-κBα phosphorylation, C/EBP and AP-1 activation.  Br J Pharmacol. 2003;  139 11-20
• 8 Lemos V S, Freitas M R, Muller B, Lino Y D, Queiroga C EG, Cortes S F. Dioclein, a new nitric oxide- and endothelium-dependent vasodilator flavonoid.  Eur J Pharmacol. 1999;  386 41-6
• 9 Privat C, Lantoine F, Bedioui F, Millanvoyc van Brussel E, Devynck J, Devynck M A. Nitric oxide production by endothelial cells: comparison of three methods of quantification.  Life Sci. 1997;  61 1193-202
• 10 Eglen R M, Reddy H, Watson N, Challiss R A. Muscarinic acetylcholine receptor subtypes in smooth muscle.  Trends Pharmacol Sci. 1994;  15 114-9
• 11 Fleming I, Busse R. NO: the primary EDRF.  J Mol Cell Cardiol. 1999;  31 5-14
• 12 Moncada S, Palmer R MJ, Higgs E A. Biosynthesis and endogenous roles of nitric oxide.  Pharmacol Rev. 1991;  43 109-42
• 13 Butler A R, Flitney F W, Williams D LH. NO, nitrosonium ions, nitroxide ions, nitrosothiols and iron-nitrosyls in biology: a chemist’s perspective.  Trends Pharmacol Sci. 1995;  16 18-22
• 14 Satoh M, Matsuo K, Kiriya H, Mashino T, Hirobe M, Takayanagi I. Inhibitory effect of a fullerene derivative, monomalonic acid C₆₀, on nitric oxide-dependent relaxation of aortic smooth muscle.  Gen Pharmacol. 1997;  29 345-51
• 15 Feelisch M, Ostrowski J, Noack E. On the mechanism of NO release from sydnonimines.  J Cardiovasc Pharmacol. 1989;  14 S13-22