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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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).
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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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