Imperatorin is responsible for the vasodilatation activity of Angelica Dahurica var. Formosana regulated by nitric oxide in an endothelium-dependent manner.
OBJECTIVE
To demonstrate the vasodilatation activity of the coumarin-containing Angelica dahurica var. formosana and to further analyze active components in the herb extracts.


METHODS
(1) The vasodilatation effects induced by different extracts (cyclohexane, ethyl acetate, acetone, methanol, 95 % ethanol and water) of Angelica dahurica var. formosana on mouse thoracic aorta pre-contracted with phenylephrine were investigated. (2) The amount of imperatorin and isoimperatorin in each extract was measured by high-performance liquid chromatography. (3) The vasodilatation effects of imperatorin and isoimperatorin on mouse thoracic aorta were compared using the same in vitro method. (4) The vasodilatation mechanism of imperatorin in the mouse thoracic aorta pre-contracted with phenylephrine was studied using the methods of denuded endothelium, NG-nitro-L-arginine methylester (L-NAME, a nitric oxide synthase inhibitor), and propranolol.


RESULTS
(1) The cyclohexane and ethyl acetate extracts of Angelica dahurica var. formosana decreased the maximal response of phenylephrine-induced mouse thoracic aorta contraction dose-dependently, with 50% inhibiting concentration (IC(50)) values of 35.3+/-12.4 mg/L and 40.5+/-12.0 mg/L, respectively. The vasodilatation effect of imperatorin and isoimperatorin was dose-dependent. (2) The cyclohexane extract, showing the strongest vasodilatation effect, possessed the highest contents of imperatorin (4.09%) and isoimperatorin (0.27%, w/w). There was a correlation between the vasodilatation activity and the contents of imperatorin and isoimperatorin in the extracts. (3) The vasodilatation effect of imperatorin was about 4-fold stronger than that of isoimperatorin. (4) The vasodilatation effect of imperatorin was signifificantly attenuated to 24.88%+/-4.06% in the denuded endothelium group compared with the intact endothelium group. And 1 mmol/L L-NAME reduced the imperatorin-induced vasorelaxation by 32.18 %+/-11.29 %.


CONCLUSIONS
The principal effective component of Angelica dahurica var. Formosana was found to be imperatorin. Imperatorin-induced vasodilatation is at least partially regulated by nitric oxide, and has no correlation to beta-receptor.
Nie
Hong
H
College of Pharmacy, Jinan University, Guangzhou, China. tnieh@jnu.edu.cn
Meng
Lan-zhen
LZ
Zhou
Jiu-yao
JY
Fan
Xiao-feng
XF
Luo-
Yong
Y
Zhang
Guang-wen
GW
D029969:Angelica / Q000737:chemistry; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000502:physiology*; D011564:Furocoumarins / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D011564:Furocoumarins; D010936:Plant Extracts; C055542:isoimperatorin; D010656:Phenylephrine; D009569:Nitric Oxide; D011433:Propranolol; C031534:imperatorin; D019331:NG-Nitroarginine Methyl Ester