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Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract
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 impro...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043734/ https://www.ncbi.nlm.nih.gov/pubmed/36998615 http://dx.doi.org/10.3389/fphar.2023.1148155 |
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author | Lee, Choong Whan You, Byoung Hoon Yim, Sreymom Han, Seung Yon Chae, Hee-Sung Bae, Mingoo Kim, Seo-Yeon Yu, Jeong-Eun Jung, Jieun Nhoek, Piseth Kim, Hojun Choi, Han Seok Chin, Young-Won Kim, Hyun Woo Choi, Young Hee |
author_facet | Lee, Choong Whan You, Byoung Hoon Yim, Sreymom Han, Seung Yon Chae, Hee-Sung Bae, Mingoo Kim, Seo-Yeon Yu, Jeong-Eun Jung, Jieun Nhoek, Piseth Kim, Hojun Choi, Han Seok Chin, Young-Won Kim, Hyun Woo Choi, Young Hee |
author_sort | Lee, Choong Whan |
collection | PubMed |
description | 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, anti-obesity, 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). |
format | Online Article Text |
id | pubmed-10043734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100437342023-03-29 Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract Lee, Choong Whan You, Byoung Hoon Yim, Sreymom Han, Seung Yon Chae, Hee-Sung Bae, Mingoo Kim, Seo-Yeon Yu, Jeong-Eun Jung, Jieun Nhoek, Piseth Kim, Hojun Choi, Han Seok Chin, Young-Won Kim, Hyun Woo Choi, Young Hee Front Pharmacol Pharmacology 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, anti-obesity, 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). Frontiers Media S.A. 2023-03-10 /pmc/articles/PMC10043734/ /pubmed/36998615 http://dx.doi.org/10.3389/fphar.2023.1148155 Text en Copyright © 2023 Lee, You, Yim, Han, Chae, Bae, Kim, Yu, Jung, Nhoek, Kim, Choi, Chin, Kim and Choi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Lee, Choong Whan You, Byoung Hoon Yim, Sreymom Han, Seung Yon Chae, Hee-Sung Bae, Mingoo Kim, Seo-Yeon Yu, Jeong-Eun Jung, Jieun Nhoek, Piseth Kim, Hojun Choi, Han Seok Chin, Young-Won Kim, Hyun Woo Choi, Young Hee Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract |
title | Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract |
title_full | Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract |
title_fullStr | Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract |
title_full_unstemmed | Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract |
title_short | Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract |
title_sort | change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043734/ https://www.ncbi.nlm.nih.gov/pubmed/36998615 http://dx.doi.org/10.3389/fphar.2023.1148155 |
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