Induction of cytochrome P450s by terpene trilactones and flavonoids of the<b><i>Ginkgo biloba</i></b>extract EGb 761 in rats

Deng, Ying; Bi, Huichang; Zhao, Lizi; He, Fan; Liu, Y.-Q.; Yu, Jianshe; Ou, Zhimin; Ding, Lianhui; Chen, X.; Huang, Zhiying; Huang, Min; Zhou, Shu‐Feng

doi:10.1080/00498250701883233

Cited by 50 publications

(31 citation statements)

References 42 publications

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“…Similar to the present rat study, bilobalide caused a marked induction of CYP enzyme, but such induction was not observed by the use of the other three terpenoids (unpublished results). A similar finding (14) reported that the inductions of CYPs in rats by ginkgolide A, B quercetin, and kaempherol were less than that caused by bilobalide. Further studies will be needed to clarify the molecular mechanism of CYPs induction by bilobalide.…”

supporting

confidence: 85%

Time-Dependent Induction of Hepatic Cytochrome P450 Enzyme Activity and mRNA Expression by Bilobalide in Rats

et al. 2009

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Abstract. A single dose by gavage of bilobalide (30 mg/kg) was found to produce a timedependent induction of hepatic cytochrome P450 (CYP) enzyme activity and protein expression in rats. An RT-PCR study further showed that mRNA expression of CYP2B was maximal at 6 h. Plasma and liver bilobalide concentration in rats following administration of Ginkgo biloba extract equivalent to bilobalide of approximately 40 mg/kg showed a similar response to that exhibited by mRNA expression. These findings suggest that bilobalide markedly induced hepatic CYPs, but the induction could be mitigated due to rapid elimination from the liver.

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supporting

confidence: 85%

Time-Dependent Induction of Hepatic Cytochrome P450 Enzyme Activity and mRNA Expression by Bilobalide in Rats

et al. 2009

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“…Previous ex vivo studies indicate that bilobalide increased rat hepatic CYP2B expression (Deng et al, 2008a;Taki et al, 2009). Likewise, in a cell culture study on rat hepatocytes, bilobalide increased the levels of CYP2B1 mRNA and enzyme activity .…”

Section: Introductionmentioning

confidence: 76%

“…However, two other ex vivo rat studies produced internally inconsistent results on the effects of bilobalide on CYP3A mRNA, protein, and enzyme activity levels, when administered as a single dose of 30 mg/kg (Taki et al, 2009) or multiple doses of 1.5 to 30 mg/kg per day for 10 days (Deng et al, 2008a). Taken together, the data from the ex vivo rat studies are inconclusive.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous ex vivo study, bilobalide increased the activity of rat hepatic microsomal CYP3A (Suzuki et al, 2004). However, data on the effect of this chemical on rat CYP3A mRNA, protein, and enzyme activity are internally inconsistent in each of the other two ex vivo studies (Deng et al, 2008a;Taki et al, 2009). In a cell culture study on rat hepatocytes, bilobalide (3-15 M) did not increase CYP3A mRNA or enzyme activity , whereas in another study, the chemical at lesser concentrations of 2 to 50 ng/ml (equivalent to 0.006 -0.153 M) was reported to apparently increase CYP3A protein expression in rat hepatocytes (Deng et al, 2008b).…”

Section: Introductionmentioning

confidence: 93%

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Species-Dependent and Receptor-Selective Action of Bilobalide on the Function of Constitutive Androstane Receptor and Pregnane X Receptor

Lau

Yang²,

Rajaraman³

et al. 2011

Drug Metab Dispos

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ABSTRACT:Bilobalide is a naturally occurring sesquiterpene trilactone with therapeutic potential in the management of ischemia and neurodegenerative diseases such as Alzheimer's disease. In the present study, we investigated the effect of bilobalide on the activity of rat constitutive androstane receptor (rCAR) and rat pregnane X receptor (rPXR) and compared that with human CAR (hCAR) and human PXR (hPXR). Bilobalide activated rCAR in a luciferase reporter gene assay and increased rCAR target gene expression in cultured rat hepatocytes, as determined by the CYP2B1 mRNA and CYP2B enzyme activity (benzyloxyresorufin O-dealkylation) assays. This increase in hepatocyte CYP2B1 expression by bilobalide was not accompanied by a corresponding increase in rCAR mRNA level. In contrast to the activation of rCAR, the activity of rPXR, hCAR, and hPXR was not influenced by this chemical in cell-based reporter gene assays. Consistent with these results, bilobalide did not alter rPXR, hCAR, or hPXR target gene expression in rat or human hepatocytes, as evaluated by the CYP3A23, CYP2B6, CYP3A4 mRNA assays and the CYP3A (testosterone 6␤-hydroxylation) and CYP2B6 (bupropion hydroxylation) enzyme activity assays. Bilobalide was not an antagonist of rPXR, hCAR, or hPXR, as suggested by the finding that it did not attenuate rPXR activation by pregnenolone 16␣-carbonitrile, hCAR activation by 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime, or hPXR activation by rifampicin in reporter gene assays. In conclusion, bilobalide is an activator of rCAR, whereas it is not a ligand of rPXR, hCAR, or hPXR. Likewise, it is an inducer of rat CYP2B1, but not of rat CYP3A23, human CYP2B6, or human CYP3A4.

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“…However, CYP1B1 is uniquely overexpressed in a wide range of human cancers of different histogenetic types compared to normal tissues (26)(27)(28). Several studies reported that the Ginkgo biloba extract exhibits differential induction of CYPs (29)(30)(31). The aim of this study was to assess whether the Ginkgo biloba extract induces CYP1B1 expression and affects the proliferation of MCF-7 and MDA-MB-231 human breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative effect of the Ginkgo biloba extract is associated with the enhancement of cytochrome P450 1B1 expression in estrogen receptor-negative breast cancer cells

Zhao

Man

et al. 2013

Biomedical Reports

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Abstract. Ginkgo biloba is a dioecious tree and its extract is a complex mixture that has been used for thousands of years to treat a variety of ailments in traditional Chinese medicine. The aim of this study was to present our observations on the inhibitory effects of different Ginkgo biloba extracts on human breast cancer cell proliferation and growth. Our results demonstrated that treatment of MCF-7 and MDA-MB-231 human breast cancer cells with Ginkgo biloba leaves and ginkgo fruit extract inhibited cell proliferation. It was also observed that this inhibition was accompanied by the enhancement of cytochrome P450 (CYP) 1B1 expression in MDA-MB-231 cells. In addition, treatment with ginkgo fruit extract resulted in a higher CYP1B1 expression in MDA-MB-231 cells compared to treatment with the Ginkgo biloba leaves extract. Our results suggested that the inhibitory effects of the Ginkgo biloba extract on estrogen receptor-negative breast cancer proliferation and the induction of CYP1B1 expression may be exerted through an alternative pathway, independent of the estrogen receptor or the aryl hydrocarbon receptor pathway.

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Induction of cytochrome P450s by terpene trilactones and flavonoids of theGinkgo bilobaextract EGb 761 in rats

Cited by 50 publications

References 42 publications

Time-Dependent Induction of Hepatic Cytochrome P450 Enzyme Activity and mRNA Expression by Bilobalide in Rats

Time-Dependent Induction of Hepatic Cytochrome P450 Enzyme Activity and mRNA Expression by Bilobalide in Rats

Species-Dependent and Receptor-Selective Action of Bilobalide on the Function of Constitutive Androstane Receptor and Pregnane X Receptor

Antiproliferative effect of the Ginkgo biloba extract is associated with the enhancement of cytochrome P450 1B1 expression in estrogen receptor-negative breast cancer cells

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