當歸成分이 肝의 藥物代謝 酵素活性에 미치는 影響

Abstract

간의 약물대사효소 활성에 현저한 영향을 미치는 것으로 豫知된 Angelica속 식물 생약중 當歸로 부터 有效成분을 糾明하고자 당귀 MeoH추출물의 係統的 分劃을 통해 얻은 각 분획물중 가장 활성이 큰 ether분획물로 부터 pyranocoumarin계열 물질인 decursin을 분리하였다. 간 약물대사에 미치는 영향에 대해서는 hexobarbital 수면시간, 혈중 hexobarbital 농도측정, aminopyrine, aniline, hexobarbital 대사량 측정 및 Cyt.p-450의 정량등을 지표로 검토한 결과 decursin을 hexobarbital 수면시간 연장, 혈중 hexobarbital 농도증가, 각종 효소활성의 감소, Cyt. P-450의 감소등을 나타내어 간의 약물대사효소 활성 억제작용이 있음이 입증되었다.;The methanolic extract of the roots of Angelica gigas exhibited a significant prolongation of hexobarbital (HB)-induced sleeping time. Systematic fractionation and liquid chromatography of an ether soluble fraction, monitoring by bio-assay, led to the isolation of an active principle which was identified as decursin, a pyranocoumarin by spectral analysis. Decursin, with a single treatment in mice was found to show not only a significant prolongation of HB-induced sleeping time but also an increase in serum HB concentration. It was also noted that decursin caused a significant inhibition of hepatic drug metabolizing enzymes such as aminopyrine N-demethylase , aniline hydroxylase and hexobarbital hydroxylase accompanied by a concomitant loss of cytochrome P-450 concentration. These findings and the results that the destruction of cytochrome P-450 by decursin in vitro required NADPH-generating system strongly suggested that cytochrome P-450 was specifically destroyed in a metabolic process and as a consequence, a significant inhibition of substrate metabolism might be occured.