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- Title
Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract.
- Authors
Choong Whan Lee; Byoung Hoon You; Sreymom Yim; Seung Yon Han; Hee-Sung Chae; Mingoo Bae; Seo-Yeon Kim; Jeong-Eun Yu; Jieun Jung; Piseth Nhoek; Hojun Kim; Han Seok Choi; Young-Won Chin; Hyun Woo Kim; Young Hee Choi
- Abstract
Metformin as an oral glucose-lowering drug is used to treat type 2 diabetic mellitus. Considering the relatively high incidence of cardiovascular complications and other metabolic diseases in diabetic mellitus patients, a combination of metformin plus herbal supplements is a preferrable way to improve the therapeutic outcomes of metformin. Ginseng berry, the fruit of Panax ginseng Meyer, has investigated as a candidate in metformin combination mainly due to its anti-hyperglycemic, anti-hyperlipidemic, antiobesity, anti-hepatic steatosis and anti-inflammatory effects. Moreover, the pharmacokinetic interaction of metformin via OCTs and MATEs leads to changes in the efficacy and/or toxicity of metformin. Thus, we assessed how ginseng berry extract (GB) affects metformin pharmacokinetics in mice, specially focusing on the effect of the treatment period (i.e., 1-day and 28-day) of GB on metformin pharmacokinetics. In 1-day and 28-day co-treatment of metformin and GB, GB did not affect renal excretion as a main elimination route of metformin and GB therefore did not change the systemic exposure of metformin. Interestingly, 28-day co-treatment of GB increased metformin concentration in the livers (i.e., 37.3, 59.3% and 60.9% increases versus 1-day metformin, 1-day metformin plus GB and 28-day metformin groups, respectively). This was probably due to the increased metformin uptake via OCT1 and decreased metformin biliary excretion via MATE1 in the livers. These results suggest that co-treatment of GB for 28 days (i.e., long-term combined treatment of GB) enhanced metformin concentration in the liver as a pharmacological target tissue of metformin. However, GB showed a negligible impact on the systemic exposure of metformin in relation to its toxicity (i.e., renal and plasma concentrations of metformin).
- Subjects
BERRIES; METFORMIN; GINSENG; DRUG interactions; LIVER; ORAL medication; ENTEROHEPATIC circulation
- Publication
Frontiers in Pharmacology, 2023, Vol 14, p1
- ISSN
1663-9812
- Publication type
Article
- DOI
10.3389/fphar.2023.1148155