Peschel Dieter, Koerting Ramona, Nass Norbert
BMBF Group Molecular Nutrition Halle, Institute of Nutritional Sciences, Martin-Luther University Halle-Wittenberg, D-06108 Halle, Germany.
J Nutr Biochem. 2007 Feb;18(2):113-9. doi: 10.1016/j.jnutbio.2006.03.007. Epub 2006 May 18.
Curcuminoids, the yellow pigments of curcuma, exhibit anticarcinogenic, antioxidative and hypocholesterolemic activities. To understand the molecular basis for the hypocholesterolemic effects, we examined the effects of curcumin on hepatic gene expression, using the human hepatoma cell line HepG2 as a model system. Curcumin treatment caused an up to sevenfold, concentration-dependent increase in LDL-receptor mRNA, whereas mRNAs of the genes encoding the sterol biosynthetic enzymes HMG CoA reductase and farnesyl diphosphate synthase were only slightly increased at high curcumin concentrations where cell viability was reduced. Expression of the regulatory SREBP genes was moderately increased, whereas mRNAs of the PPARalpha target genes CD36/fatty acid translocase and fatty acid binding protein 1 were down-regulated. LXRalpha expression and accumulation of mRNA of the LXRalpha target gene ABCg1 were increased at low curcumin concentrations. Although curcumin strongly inhibited alkaline phosphatase activity, an activation of a retinoic acid response element reporter employing secreted alkaline phosphatase was observed. These changes in gene expression are consistent with the proposed hypocholesterolemic effect of curcumin.
姜黄素类化合物是姜黄中的黄色色素，具有抗癌、抗氧化和降胆固醇活性。为了解降胆固醇作用的分子基础，我们以人肝癌细胞系HepG2为模型系统，研究了姜黄素对肝脏基因表达的影响。姜黄素处理使低密度脂蛋白受体mRNA增加了7倍，呈浓度依赖性，而编码固醇生物合成酶HMG CoA还原酶和法尼基二磷酸合酶的基因的mRNA在高姜黄素浓度下仅略有增加，此时细胞活力降低。调节性SREBP基因的表达适度增加，而PPARα靶基因CD36/脂肪酸转运蛋白和脂肪酸结合蛋白1的mRNA则下调。在低姜黄素浓度下，LXRα表达和LXRα靶基因ABCg1的mRNA积累增加。尽管姜黄素强烈抑制碱性磷酸酶活性，但观察到使用分泌型碱性磷酸酶的视黄酸反应元件报告基因的激活。这些基因表达的变化与姜黄素拟议的降胆固醇作用一致。
