Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Pharmacokinetic and Pharmacodynamic Interaction between Metformin and (-)-Epigallocatechin-3-gallate

  • Ko, Jeong-Hyeon (Department of Pharmacology and Medicinal Toxicology Research Center, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project) ;
  • Jang, Eun-Hee (Department of Pharmacology and Medicinal Toxicology Research Center, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project) ;
  • Park, Chang-Shin (Department of Pharmacology and Medicinal Toxicology Research Center, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project) ;
  • Kim, Hyoung-Kwang (Department of Pharmacology and Medicinal Toxicology Research Center, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project) ;
  • Cho, Soon-Gu (Department of Radiology, Inha University Hospital) ;
  • Shin, Dong-Wun (Department of Emergency Medicine, Inje University Ilsan Paik Hospital) ;
  • Yi, Hyeon-Gyu (Department of Internal Medicine, Inha University Hospital) ;
  • Kang, Ju-Hee (Department of Pharmacology and Medicinal Toxicology Research Center, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project)
  • Published : 2009.12.31
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Abstract

(-)-Epigallocatechin-3-gallate (EGCG), a major flavonoid in green tea has multiple health benefits including chemoprevention, anti-inflammatory, anti-diabetic, and anti-obesity effects. In connection with these effects, EGCG can be a candidate to help the treatment of metabolic diseases. Metformin is a widely used anti-diabetic drug regulating cellular energy homeostasis via AMP-activated protein kinase (AMPK) activation. Therefore, the combination of metformin with EGCG may have additive or synergistic effects on treatment of type 2 diabetes. Nevertheless, there is no report for the pharmacokinetic and/or pharmacodynamic interaction of EGCG with metformin. Here, we evaluated the pharmacokinetic and pharmacodynamic interaction between metformin and EGCG in rats. Pharmacokinetics parameters of metformin were measured after oral administration of metformin in rats pre-treated with EGCG (10 mg/kg) or saline for 7 days. The results showed that there is no significant difference in pharmacokinetic parameters between saline control and EGCG-treated group. In addition, the hepatic AMPK activation by metformin in EGCG-treated rats was also similar to the control. The lack of additive effects of EGCG on AMPK activation or intracellular uptake of metformin was also evaluated in cells in the presence or absence of EGCG. Treatment of HepG2 cells with EGCG inhibited the metformin-induced AMPK activation. Combined results suggested that EGCG has no effect on the pharmacokinetics of metformin but may contribute to metformin action.

Keywords

References

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