Artery Relaxation by Chalcones Isolated from the Roots of Angelica keiskei

Abstract

An EtOAc-soluble fraction from a 50 % EtOH extract of the roots of Angelica keiskei inhibited phenylephrine-induced vasoconstriction in rat aortic rings, while an EtOAc-insoluble fraction had no effect at 100 μg/ml. Five active substances isolated from the EtOAc-soluble fraction of the roots were identified as xanthoangelol (1), 4-hydroxyderricin (2), and xanthoangelols B (3), E (4) and F (5), which inhibited phenylephrine-induced vasoconstriction at the concentrations of 10 - 100 μg/ml. It was found that xanthoangelol (1), 4-hydroxyderricin (2), and xanthoangelols E (4) and F (5) inhibited the phenylephrine-induced vasoconstriction through endothelium-dependent endothelium-derived relaxing factor (EDRF) production and/or nitric oxide (NO) production. Among the five chalcones, xanthoangelol B (3) inhibited the phenylephrine-induced vasoconstriction most strongly, and it inhibited the phenylephrine-induced vasoconstriction in the presence or absence of endothelium and in the presence or absence of N ^G-monomethyl-L-arginine (L-NMMA) (an NO synthetase inhibitor). Furthermore, 4-hydroxyderricin (2) and xanthoangelol B (3) at concentrations of 10 - 100 μg/ml concentration-dependently inhibited the elevation of intracellular free calcium [Ca²⁺]i induced by phenylephrine. These results demonstrate that compounds 1, 2, 4 and 5 inhibit phenylephrine-induced vasoconstriction through endothelium-dependent production of EDRF/NO and/or through the reduction of the [Ca²⁺]i elevation induced by phenylephrine. On the other hand, the inhibitory mechanism of compound 3 on phenylephrine-induced vasoconstriction might involve the direct inhibition of smooth muscle functions through the reduction of [Ca²⁺]i elevation without affecting EDRF/NO production.

Artery relaxation - endothelium - chalcones - Angelica keiskei - Umbelliferae

References

• 1 Kozawa M, Morita N, Baba K, Hata K. The structure of xanthoangelol, a new chalcone from the roots of Angelica keiskei Koidzumi (Umbelliferae).  Chem. Pharm. Bull.. 1977;  25 515-6
• 2 Kozawa M, Morita N, Baba K, Hata K. Chemical components of the roots of Angelica keiskei Koidzumi. II. The structure of the chalcone derivatives.  Yakugaku Zasshi. 1978;  98 210-4
• 3 Baba K, Nakata K, Taniguchi M, Kido T, Kozawa M. Chalcones from Angelica keiskei .  Phytochemistry. 1990;  29 3907-10
• 4 Nakata K, Taniguchi M, Baba K. Three new chalcones from Angelica keiskei .  Natural Med. (Shouyakugaku Zasshi). 1999;  53 329-32
• 5 Collins P, Burman J, Chung H-I, Fox K. Hemoglobin inhibits endothelium-dependent relaxation to acetylcholine in human cornary arteries in vivo .  Circulation. 1993;  87 80-5
• 6 Furchgott R F, Zawadzki J V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.  Nature. 1980;  288 373-6
• 7 Vallance P, Collier J, Moncada S. Effect of endothelium-derived nitric oxide on periphral arteriolar tone in man.  Lancet. 1989;  28 997-1000
• 8 Sinoway L I, Hendrickson C, Davidson W R, Prophet S, Zelis R. Characteristics of flow-mediated branchial artery vasodilation in human subjects.  Circ. Res.. 1989;  64 32-42
• 9 Rapoport R M, Murad F. Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP.  Circ. Res.. 1983;  52 352-7
• 10 Rapoport R M, Waldman S A, Schwartz K, Winquist R J, Murad F. Effects of atrial natriuretic factor, sodium nitroprusside, and acetylcholine on cyclic GMP levels and relaxation in rat aorta.  Eur. J. Pharmacol.. 1985;  115 219-29
• 11 MacCullon A I, Bottrill F E, Randakk M D, Hiley C R. Characterization and modulation of EDHF-mediated relaxations in the rat isolated superior mesenteric arteila bed.  Br. J. Pharmacol.. 1997;  120 1431-8
• 12 Nabel E G, Selwyn A P, Ganz P. Large coronary arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis.  J. Am. Coll. Cardiol.. 1990;  16 349-56
• 13 Drexler H, Zeiher A M, Wollschläger H, Meinertz J, Bonzel T. Flow-dependent coronary artery dilation in humans.  Circulation. 1989;  80 466-74
• 14 Rubhanyi G M, Romero J C, Vanhoutte P M. Flow-induced release of endothelium-derived relaxing factor.  Am. J. Physiol.. 1986;  250 H1145-9
• 15 Sessa W C, Pritchard K, Seyedi N, Wang J, Hintze T H. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression.  Circ. Res.. 1994;  74 349-53