{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:58:40Z","timestamp":1780621120450,"version":"3.54.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>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 <jats:italic>Panax ginseng<\/jats:italic> 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 <jats:italic>via<\/jats:italic> 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 <jats:italic>versus<\/jats:italic> 1-day metformin, 1-day metformin plus GB and 28-day metformin groups, respectively). This was probably due to the increased metformin uptake <jats:italic>via<\/jats:italic> OCT1 and decreased metformin biliary excretion <jats:italic>via<\/jats:italic> MATE1 in the livers. These results suggest that co-treatment of GB for 28\u00a0days (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).<\/jats:p>","DOI":"10.3389\/fphar.2023.1148155","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T04:40:54Z","timestamp":1678423254000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract"],"prefix":"10.3389","volume":"14","author":[{"given":"Choong Whan","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung Hoon","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreymom","family":"Yim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Yon","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Sung","family":"Chae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingoo","family":"Bae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo-Yeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Eun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieun","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piseth","family":"Nhoek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hojun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Seok","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Won","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Woo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Hee","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.ejps.2016.03.020","article-title":"Metformin and cimetidine: Physiologically based pharmacokinetic modelling to investigate transporter mediated drug-drug interactions","volume":"88","author":"Burt","year":"2016","journal-title":"Eur. 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