Xie Zuo-quan, Liang Gai, Zhang Lu, Wang Qi, Qu Yi, Gao Yang, Lin Li-bo, Ye Sai, Zhang Ji, Wang Hui, Zhao Guo-ping, Zhang Qing-hua
State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Acta Pharmacol Sin. 2009 Sep;30(9):1262-75. doi: 10.1038/aps.2009.126. Epub 2009 Aug 24.
To explore the molecular mechanisms underlying the cholesterol-lowering effect of a Ginkgo biloba extract (GBE).
Enzyme activity, cholesterol flux and changes in gene expression levels were assessed in cultured hepatocytes treated with GBE or lovastatin.
GBE decreased the total cholesterol content in cultured hepatocytes and inhibited the activity of HMG-CoA reductase, as determined by an in vitro enzyme activity assay. In addition, GBE decreased cholesterol influx, whereas lovastatin increased cholesterol influx. GBE treatment induced significant increases in the expression of cholesterogenic genes and genes involved in cholesterol metabolism, such as SREBF2, as determined by cDNA microarray and real-time RT-PCR. Furthermore, INSIG2, LDLR, LRP1, and LRP10 were differentially regulated by GBE and lovastatin. The data imply that the two compounds modulate cholesterol metabolism through distinct mechanisms.
By using a gene expression profiling approach, we were able to broaden the understanding of the molecular mechanisms by which GBE lowers cellular cholesterol levels. Specifically, we demonstrated that GBE exhibited dual effects on the cellular cholesterol pool by modulating both HMG-CoA reductase activity and inhibiting cholesterol influx.
探讨银杏叶提取物（GBE）降胆固醇作用的分子机制。
在用GBE或洛伐他汀处理的培养肝细胞中评估酶活性、胆固醇通量及基因表达水平的变化。
通过体外酶活性测定发现，GBE降低了培养肝细胞中的总胆固醇含量，并抑制了HMG-CoA还原酶的活性。此外，GBE降低了胆固醇内流，而洛伐他汀增加了胆固醇内流。通过cDNA微阵列和实时逆转录聚合酶链反应测定，GBE处理显著增加了胆固醇生成基因和参与胆固醇代谢的基因（如SREBF2）的表达。此外，GBE和洛伐他汀对INSIG2、LDLR、LRP1和LRP10的调节存在差异。数据表明这两种化合物通过不同机制调节胆固醇代谢。
通过基因表达谱分析方法，我们能够拓宽对GBE降低细胞胆固醇水平分子机制的理解。具体而言，我们证明GBE通过调节HMG-CoA还原酶活性和抑制胆固醇内流，对细胞胆固醇池产生双重作用。
