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

Xie ZQ, Liang G, Zhang L, Wang Q, Qu Y, Gao Y, Lin LB, Ye S, Zhang J, Wang H, Zhao GP, Zhang QH - Acta Pharmacol. Sin. (2009)

Bottom Line: 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.Specifically, we demonstrated that GBE exhibited dual effects on the cellular cholesterol pool by modulating both HMG-CoA reductase activity and inhibiting cholesterol influx.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

ABSTRACT

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

Methods: Enzyme activity, cholesterol flux and changes in gene expression levels were assessed in cultured hepatocytes treated with GBE or lovastatin.

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.

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Western blot analysis of HMGCR and SREBP2 proteins. (A) Western blots images, (B) Signal quantitation of each band. β-actin was immuno-probed as a loading control. HMGCR was induced by both GBE50 and lovastatin, but the lovastatin had a stronger effect. The SREBP2 c-terminus was induced by GBE50 and lovastatin. The cleaved form of n-terminus nSREBP2 was upregulated by lovastatin, but not GBE50.
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fig5: Western blot analysis of HMGCR and SREBP2 proteins. (A) Western blots images, (B) Signal quantitation of each band. β-actin was immuno-probed as a loading control. HMGCR was induced by both GBE50 and lovastatin, but the lovastatin had a stronger effect. The SREBP2 c-terminus was induced by GBE50 and lovastatin. The cleaved form of n-terminus nSREBP2 was upregulated by lovastatin, but not GBE50.

Mentions: We further examined 20 cholesterol metabolism-related genes by real-time RT-PCR. We identified that the mRNA levels of HMGCR and SREBF2 (encoding sterol regulatory element-binding protein 2) were upregulated by GBE. On the other hand, the mRNA level of the SREBF chaperone (SCAP) was downregulated by GBE (Figure 4A). The protein level of both HMGCR and SREBF2 encoding protein SREBP2 was also increased (Figure 5). Interestingly, insulin-induced gene 2 (INSIG2) was upregulated by GBE, but downregulated by lovastatin.


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

Xie ZQ, Liang G, Zhang L, Wang Q, Qu Y, Gao Y, Lin LB, Ye S, Zhang J, Wang H, Zhao GP, Zhang QH - Acta Pharmacol. Sin. (2009)

Western blot analysis of HMGCR and SREBP2 proteins. (A) Western blots images, (B) Signal quantitation of each band. β-actin was immuno-probed as a loading control. HMGCR was induced by both GBE50 and lovastatin, but the lovastatin had a stronger effect. The SREBP2 c-terminus was induced by GBE50 and lovastatin. The cleaved form of n-terminus nSREBP2 was upregulated by lovastatin, but not GBE50.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4007179&req=5

fig5: Western blot analysis of HMGCR and SREBP2 proteins. (A) Western blots images, (B) Signal quantitation of each band. β-actin was immuno-probed as a loading control. HMGCR was induced by both GBE50 and lovastatin, but the lovastatin had a stronger effect. The SREBP2 c-terminus was induced by GBE50 and lovastatin. The cleaved form of n-terminus nSREBP2 was upregulated by lovastatin, but not GBE50.
Mentions: We further examined 20 cholesterol metabolism-related genes by real-time RT-PCR. We identified that the mRNA levels of HMGCR and SREBF2 (encoding sterol regulatory element-binding protein 2) were upregulated by GBE. On the other hand, the mRNA level of the SREBF chaperone (SCAP) was downregulated by GBE (Figure 4A). The protein level of both HMGCR and SREBF2 encoding protein SREBP2 was also increased (Figure 5). Interestingly, insulin-induced gene 2 (INSIG2) was upregulated by GBE, but downregulated by lovastatin.

Bottom Line: 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.Specifically, we demonstrated that GBE exhibited dual effects on the cellular cholesterol pool by modulating both HMG-CoA reductase activity and inhibiting cholesterol influx.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

ABSTRACT

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

Methods: Enzyme activity, cholesterol flux and changes in gene expression levels were assessed in cultured hepatocytes treated with GBE or lovastatin.

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.

Show MeSH
Related in: MedlinePlus