Molecular target of piperine in the inhibition of lipid droplet accumulation in macrophages
Molecular target of piperine in the inhibition of lipid droplet accumulation in macrophages
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DOI：
10.1248/bpb.31.1063
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发表时间：
2008-06-01
影响因子：
2
通讯作者：
Tomoda, Hiroshi
中科院分区：
文献类型：
--
作者：
Matsuda, Daisuke;Ohte, Satoshi;Tomoda, Hiroshi
发现从胡椒属植物中分离的生物碱胡椒碱抑制小鼠巨噬细胞中的脂滴积累，特别是抑制胆固醇酯（CE）合成（IC 50：25 μ M）。胆固醇从溶酶体到脂滴的代谢被抑制，IC_（50）相似（18 μ M），表明抑制位点是溶酶体和内质网之间的步骤之一。因此，研究了胡椒碱对从小鼠巨噬细胞和肝脏制备的微粒体中酰基辅酶A：胆固醇酰基转移酶（ACAT）活性的影响，以表明化合物在两种情况下都抑制活性（IC 50：分别为9.1，7.0 μ M）。此外，胡椒碱在使用ACAT 1或ACAT 2表达细胞的基于细胞的测定中发现抑制ACAT 1和ACAT 2同工酶的程度相似（IC 50：分别为16，18 μ M）。因此，表明胡椒碱抑制巨噬细胞ACAT以减少CE合成，导致脂滴减少。
An alkaloid piperine isolated from the Piper Nigrum was found to inhibit lipid droplet accumulation in mouse macrophages, and especially inhibited cholesteryl ester (CE) synthesis (IC50: 25 mu M). The metabolism of cholesterol from lysosome to lipid droplet was inhibited with a similar IC50 (18 mu M), indicating that the site of inhibition is one of the steps between the lysosomes and the endoplasmic reticulum. Therefore, effects of piperine on acyl-CoA:cholesterol acyltransferase (ACAT) activity in the microsomes prepared from mouse macrophage and liver were studied, to show that the compounds inhibited the activity in both cases (IC50: 9.1, 7.0 mu M, respectively). Furthermore, piperine,vas found to inhibit both ACAT1 and ACAT2 isozymes to a similar extent (IC50: 16, 18 mu M respectively) in cell-based assays using ACAT1- or ACAT2-expressing cells. Thus, it was suggested that piperine inhibited macrophage ACAT to decrease CE synthesis, leading to a reduction of lipid droplets.