Acta Pharmacologica Sinica (2009) 30: 1262–1275; doi: 10.1038/aps.2009.126

Acta Pharmacologica Sinica (2009) 30: 1262–1275; doi: 10.1038/aps.2009.126; published online 24 August 2009

Original Article

Molecular mechanisms underlying the cholesterol-lowering effect of Ginkgo biloba extract in hepatocytes: a comparative study with lovastatin

Zuo-quan XIE^{1, 2}, Gai LIANG³, Lu ZHANG^{1, 2}, Qi WANG², Yi QU², Yang GAO², Li-bo LIN², Sai YE², Ji ZHANG¹, Hui WANG³, Guo-ping ZHAO^{2, 4}, Qing-hua ZHANG^{1, 2, 4, *}

¹State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; ²National Engineering Center for Biochip at Shanghai and Shanghai Biochip Co ltd, Shanghai 201203, China; ³Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; ⁴Shanghai-MOST Key Laboratory of Health and Disease Genomics, Shanghai 201203, China

Aim: To explore the molecular mechanisms underlying the cholesterol-lowering effect of a Ginkgo biloba extract (GBE).

Methods: To explore the molecular mechanisms underlying the cholesterol-lowering effect of a Ginkgo biloba extract (GBE).

Results: 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.

Conclusion: 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.

Keywords: Ginkgo biloba extract; cholesterol; HMG-CoA reductase; influx; lovastatin; microarray

This work was financially supported by grants from the Chinese National High Tech Program (863-2003AA2032) and the Development Projects of Shanghai Commission of Science and Technology (03DZ19551, 05DZ19738, 06DZ19727).

We thank Hua-sheng XIAO, Zhi-dong ZHU, Jun-song HAN, Kai SONG, and Huai-guang SONG of the SBC for their technical support and constructive comments. We also thank Dr Qing ZHANG of Shanghai Institute of Plant Physiology and Ecology for help with liquid scintillation measurements. We thank Qi GAO and Guo-an ZHANG of Shanghai Xingling Pharmaceutical Co for providing the Ginkgo biloba extract products and their support.

The original microarray data have been submitted to GEO (accession number GSE11830).
* To whom correspondence should be addressed.
Emal qinghua_zhang@shbiochip.com
Received 2008-12-29 Accepted 2009-03-09

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