Artery relaxation by chalcones isolated from the roots of Angelica keiskei.
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 micrograms/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 micrograms/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 NG-monomethyl-L-arginine (L-NMMA) (an NO synthetase inhibitor). Furthermore, 4-hydroxyderricin (2) and xanthoangelol B (3) at concentrations of 10-100 micrograms/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.
Matsuura
M
M
Second Department of Medical Biochemistry, School of Medicine, Ehime University, Ehime, Japan.
Kimura
Y
Y
Nakata
K
K
Baba
K
K
Okuda
H
H
D000818:Animals; D001011:Aorta / Q000187:drug effects; D019661:Apiaceae / Q000737:chemistry*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002599:Chalcone / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D046508:Culture Techniques; D006152:Cyclic GMP / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D010936:Plant Extracts; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D002599:Chalcone; D006152:Cyclic GMP; D002118:Calcium