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후박 잎에서 분리한 Acyl-CoA

후박 잎에서 분리한 Acyl-CoA
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대학원 약학과
이화여자대학교 대학원
Atherosclerosis is a major death cause in western industrialized contries. A diagnosing system, medical prevention, and treatment of it is not sufficient so far. A direct acting antiatherosclerotic agent is eagerly waited. Acyl CoA:Cholesterol Acyltransferase(ACAT) is responsible for the acylation of cholesterol to cholesteryl esters, a transformation which can be essential in not only cholesteryl esters accumulation at arterial walls but also the absorption of cholesterol in the intestine and the excretion of cholesterol in the liver. Therefore, ACAT inhibitor is an attractive target for prediction and treatment of hypercholesterolemia and atherosclerosis. In these recent years the pharmaceutical experimental data demonstrated that the therapeutical potential of an ACAT inhibitor can be markedly enhanced when the compound directly affects ACAT activity in target tissues such as the liver or the arterial wall. A large number of synthetic and microbial ACAT inhibitors have been reported. However, the inhibitors have not been used clinically because of various side effects including hepatic toxicity. Therefore, new types of ACAT inhibitor are highly demanded to develope as a hypolipidemic as well as antiatherosclerotic agent. In the course of searching ACAT inhibitors from natural plant sources, the extract of Machilus thunbergii leaves was showed inhibition activity for ACAT enzyme assay system using rat liver microsomes. In order to identify the active compound for ACAT inhibition, we carried out c18 column chromatography, silicagel column chromatography, HPLC so as to separate a neolignan of benzofuran type, licarin A. This compound inhibited ACAT with an IC_(50) of 25 ㎍/㎖, and it's methyl ether(acuminatin) was synthesized and it's IC_(50) for ACAT was 12.5 ㎍/㎖. These results suggest that licarin A and acuminatin would be used as antiatherosclerotic agents by inhibition of ACAT.;천연물로부터 새로운 형태의 ACAT 저해물질을 검색하는 과정중에 후박잎의 추출물로부터 그 활성을 확인하였다. 후박(Machilus thunbergii Sieb and Zucc.)은 녹나무과(Lauraceae) 식물로 주로 수피를 약용으로 사용하여 왔다. 본 실험에서는 후박 잎으로부터 ACAT 저해활성을 확인하였으므로 그 성분을 밝히고자 C_(18) column chromatography, silicagel column chroma-tography, HPLC 과정을 수행하여, benzofuran 형의 neolignan 계 물질인 licarin A를 분리하였다. licarin A의 ACAT에 대한 IC_(50)값은 25㎍/㎖였으며, 그 유도체 O-methyl ether(acuminatin)을 합성하여 ACAT 활성 저해도를 측정한 결과 IC_(50) 값은 12.5㎍/㎖이었다. 이상의 사실로 미루어 불 때, ACAT 저해활성을 보인 licarin A및 그 유도체 acuminatin은 고콜레스테롤혈증과 동맥경화증의 치료에 효과적일 것으로 사료된다.
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