Ginkgo biloba extract modifies hypoglycemic action of tolbutamide via hepatic cytochrome P450 mediated mechanism in aged rats

Sugiyama, Tomomi; Kubota, Yōko; Shinozuka, Kazumasa; Yamada, Shizuo; Wu, Jingsong; Umegaki, Keizo

doi:10.1016/j.lfs.2004.02.020

Cited by 47 publications

(32 citation statements)

References 27 publications

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“…In our previous study, we showed that Ginkgo biloba extract attenuated the hypoglycemic action of tolbutamide via a hepatic CYP enzyme-mediated mechanism in rats, and that the effect was more pronounced in aged rats (19 months old) than in young rats (7 weeks old) 18) . Therefore, if we examine aged rats, the interaction of tolbutamide with CFE might be more marked.…”

Section: Discussionmentioning

confidence: 91%

“…However, it is important to consider the in vivo experimental conditions. For example, we previously showed that pretreatment with Ginkgo biloba extract enhanced hepatic CYP2C activity and attenuated the hypoglycemic action of tolbutamide, while simultaneous administration of Ginkgo biloba extract and tolbutamide enhanced this hypoglycemic action 18) . This appears to be due to competitive inhibition between the CYP-inducing substance and tolbutamide for CYP2C, resulting in delayed metabolism and enhanced hypoglycemic action of tolbutamide.…”

Section: Discussionmentioning

confidence: 98%

“…Tolbutamide is metabolized by CYP2C9 in humans and by CYP2C11 in rats 17) , but the activity of both enzymes can be evaluated as (S)-warfarin hydroxylase activity 18) . In the present study in rats, we observed an interaction of CFE with tolbutamide in vivo, in terms of hypoglycemia and induction of hepatic CYP2C.…”

Section: Discussionmentioning

confidence: 99%

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Coleus forskohlii Extract Attenuates the Hypoglycemic Effect of Tolbutamide in vivo via a Hepatic Cytochrome P450-Mediated Mechanism

Yokotani

Chiba

Sato

et al. 2014

Journal of the Food Hygienics Society of Japan

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This in vivo study in rats evaluated whether Coleus forskohlii extract (CFE) taken orally interacted with tolbutamide, a hypoglycemic drug metabolized by CYP2C enzymes. Rats were fed 0 , 0.3 , 1 (w/w) CFE diet for 2 weeks, followed by 0 CFE diet for 1 day. They were then given 40 mg/kg tolbutamide by intragastric gavage. Blood glucose level was determined up to 6 h after tolbutamide administration. CFE treatment increased total CYP content and various CYP subtypes in the liver. In particular, increases in activity and protein expression were noted for the CYP2B, CY-P2C, and CYP3A subtypes. CFE treatment dose-dependently attenuated both the hypoglycemic action of tolbutamide at 6 h and the plasma concentration of tolbutamide. The activity of (S)-warfarin 7-hydroxylase, a CYP2C enzyme was negatively correlated with plasma tolbutamide level, which also showed a negative correlation with the reduction of blood glucose level. These results indicate that CFE induced hepatic CYPs in rats and attenuated the hypoglycemic action of tolbutamide via a hepatic CYP2C-mediated mechanism.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 98%

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Coleus forskohlii Extract Attenuates the Hypoglycemic Effect of Tolbutamide in vivo via a Hepatic Cytochrome P450-Mediated Mechanism

Yokotani

Chiba

Sato

et al. 2014

Journal of the Food Hygienics Society of Japan

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“…Similar observations were reported for tolbutamide. The effect of chronic administration of ginkgo biloba on the pharmacokinetics of tolbutamide was investigated in rats (103), and also in healthy male volunteers (104). It was observed to attenuate the hypoglyceamic effect of tolbutamide (probe for CYP2C9) by increasing its rate of metabolism and decreasing its plasma concentrations.…”

Section: Ginseng (Panax Ginseng Asian Ginseng or Korean Ginseng)mentioning

confidence: 99%

Herbal drugs and drug interactions

Dülger¹

2012

mpj

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Pharmacodynamic interactions may be due to additive or synergistic effects which results in enhanced effect or toxicity, or herbal medicines with antagonistic properties reduce drug efficacy and result in therapeutic failure. For exampla, St John's wort may have synergistic effects with other antidepressant drugs used by the patient, resulting in increased CNS effects.Herbals like ginseng, ginkgo, garlic, ginger were reported to increase bleeding time, thus potentiating the effect of anticoagulant and antithrombotic agents. In conclusion, patients should be warned against the interaction between the herbal products and conventional medicines.

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“…In previous studies, we found that feeding GBE to rats markedly increased the concentration of hepatic cytochrome P450 (CYP), the expression of various CYP mRNAs, and the activity of some enzymes (3,4). Moreover, we reported that pretreatment of rats with GBE attenuated the efficacy of co-administered drugs such as tolbutamide (5). Reports of GBE-drug interactions in clinical studies are inconsistent; some showed interactions (6, 7), but others did not (8 -10).…”

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confidence: 99%

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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Ginkgo biloba extract modifies hypoglycemic action of tolbutamide via hepatic cytochrome P450 mediated mechanism in aged rats

Cited by 47 publications

References 27 publications

<i>Coleus forskohlii</i> Extract Attenuates the Hypoglycemic Effect of Tolbutamide <i>in vivo via</i> a Hepatic Cytochrome P450-Mediated Mechanism

<i>Coleus forskohlii</i> Extract Attenuates the Hypoglycemic Effect of Tolbutamide <i>in vivo via</i> a Hepatic Cytochrome P450-Mediated Mechanism

Herbal drugs and drug interactions

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

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