Molecular Target of Decursins in the Inhibition of Lipid Droplet Accumulation in Macrophages(Pharmacognosy)

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概要

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• During screening for inhibitors of lipid droplet accumulation in mouse peritoneal macrophages, two coumarins identified as decursin and decursinol angelate were isolated from the roots of Angelicae gigantis. The cellular molecular target of these inhibitors in macrophages was studied. Decursin and decursinol angelate inhibited cholesteryl ester (CE) synthesis with IC_<50> values of 9.7 and 10.1μM, respectively, whereas they enhanced triacylglycerol (TG) synthesis. Lysosomal metabolism of cholesterol to CE was inhibited by the compounds, indicating that the site of inhibition is one of the steps between the exiting of cholesterol from the lysosomes and CE synthesis in the endoplasmic reticulum. Therefore, acyl-CoA: cholesterol acyltransferase (ACAT) activity in the microsomal fractions prepared from mouse macrophages was studied, and the results showed inhibition of this activity by decursin and decursinol angelate with IC_<50> values of 43 and 22μM, respectively. Thus, it was concluded that the compounds inhibit macrophage ACAT activity to decrease CE synthesis, leading to a reduction of lipid droplets in macrophages.

• 公益社団法人日本薬学会の論文
• 2006-05-01

著者

• Takayanagi H

  School Of Pharmaceutical Sciences Kitasato University

• Takayanagi H

  Kitasato Univ. Tokyo Jpn

• Kawagishi Hirokazu

  Department Of Applied Biological Chemistry Faculty Of Agriculture Shizuoka University

• TOMODA Hiroshi

  School of Pharmacy, Kitasato University

• Namatame I

  Kitasato Institute For Life Sciences And Graduate School Of Infection Control Sciences Kitasato Univ

• Tomoda Hiroshi

  School Of Pharmaceutical Sciences Kitasato University

• NAMATAME Ichiji

  Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato Uni

• Ohshiro Taichi

  Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato Uni

• Toyama Hirohide

  Institute For Chemical Research Kyoto University

• Ohshiro Taichi

  Graduate School Of Pharmaceutical Sciences Kitasato University:(present Office)department Of Medhici

• Namatame Ichiji

  Kitasato Institute For Life Sciences And Graduate School Of Infection Control Sciences Kitasato Univ

• LEE Eun

  PNE Co., Ltd.

• Lee Eun

  Pne Co. Ltd.

• Kawagishi Hirokazu

  Department Of Applied Biochemistry Faculty Of Agriculture Shizuoka University

• KAWAGISHI Hirokazu

  Department of Agricultural Chemistry, Faculty of Agriculture

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