{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:06:41Z","timestamp":1787317601600,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T00:00:00Z","timestamp":1608681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000063","name":"Office of Dietary Supplements","doi-asserted-by":"publisher","award":["U54 AT008909\u201006"],"award-info":[{"award-number":["U54 AT008909\u201006"]}],"id":[{"id":"10.13039\/100000063","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:p>\n                    The botanical natural product goldenseal can precipitate clinical drug interactions by inhibiting cytochrome P450 (CYP) 3A and CYP2D6. Besides P\u2010glycoprotein, effects of goldenseal on other clinically relevant transporters remain unknown. Established transporter\u2010expressing cell systems were used to determine the inhibitory effects of a goldenseal extract, standardized to the major alkaloid berberine, on transporter activity. Using recommended basic models, the extract was predicted to inhibit the efflux transporter BCRP and uptake transporters OATP1B1\/3. Using a cocktail approach, effects of the goldenseal product on BCRP, OATP1B1\/3, OATs, OCTs, MATEs, and CYP3A were next evaluated in 16 healthy volunteers. As expected, goldenseal increased the area under the plasma concentration\u2010time curve (AUC\n                    <jats:sub>0\u2013inf<\/jats:sub>\n                    ) of midazolam (CYP3A; positive control), with a geometric mean ratio (GMR) (90% confidence interval (CI)) of 1.43 (1.35\u20131.53). However, goldenseal had no effects on the pharmacokinetics of rosuvastatin (BCRP and OATP1B1\/3) and furosemide (OAT1\/3); decreased metformin (OCT1\/2, MATE1\/2\u2010K) AUC\n                    <jats:sub>0\u2013inf<\/jats:sub>\n                    (GMR, 0.77 (0.71\u20130.83)); and had no effect on metformin half\u2010life and renal clearance. Results indicated that goldenseal altered intestinal permeability, transport, and\/or other processes involved in metformin absorption, which may have unfavorable effects on glucose control. Inconsistencies between model predictions and pharmacokinetic outcomes prompt further refinement of current basic models to include differential transporter expression in relevant organs and intestinal degradation\/metabolism of the precipitant(s). Such refinement should improve\n                    <jats:italic>in vitro<\/jats:italic>\n                    \u2010\n                    <jats:italic>in vivo<\/jats:italic>\n                    prediction accuracy, contributing to a standard approach for studying transporter\u2010mediated natural product\u2010drug interactions.\n                  <\/jats:p>","DOI":"10.1002\/cpt.2107","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T07:04:59Z","timestamp":1605078299000},"page":"1342-1352","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Assessing Transporter\u2010Mediated Natural Product\u2010Drug Interactions Via\n                    <i>In vitro<\/i>\n                    \u2010\n                    <i>In Vivo<\/i>\n                    Extrapolation: Clinical Evaluation With a Probe Cocktail"],"prefix":"10.1111","volume":"109","author":[{"given":"James T.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan\u2010Dan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakshit S.","family":"Tanna","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deena L.","family":"Hadi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington USA"},{"name":"Center of Excellence for Natural Product Drug Interaction Research Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Bansal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justina C.","family":"Calamia","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Arian","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Shireman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1lint","family":"Moln\u00e1r","sequence":"additional","affiliation":[{"name":"SOLVO Biotechnology SZTE Biol\u00f3giai Ep\u00fclet University of Szeged Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikl\u00f3s","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"SOLVO Biotechnology SZTE Biol\u00f3giai Ep\u00fclet University of Szeged Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua J.","family":"Kellogg","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of North Carolina at Greensboro Greensboro North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew E.","family":"Layton","sequence":"additional","affiliation":[{"name":"Elson S. Floyd College of Medicine Washington State University Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja B.","family":"Cech","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product Drug Interaction Research Spokane Washington USA"},{"name":"Department of Chemistry and Biochemistry University of North Carolina at Greensboro Greensboro North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Boyce","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product Drug Interaction Research Spokane Washington USA"},{"name":"Department of Biomedical Informatics University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jashvant D.","family":"Unadkat","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product Drug Interaction Research Spokane Washington USA"},{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth E.","family":"Thummel","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product Drug Interaction Research Spokane Washington USA"},{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary F.","family":"Paine","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington USA"},{"name":"Center of Excellence for Natural Product Drug Interaction Research Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,23]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"Natural Products Association.Natural Products Association Members Reflect on DSHEA at 25 Years<https:\/\/www.npanational.org\/news\/25th\u2010anniversary\u2010of\u2010dshea\u2010npa\u2010board\/> (2019). Accessed March 20 2020."},{"key":"e_1_2_10_2_1","first-page":"62","article-title":"Herbal supplement sales in US increase by 9.4% in 2018","volume":"123","author":"Smith T.","year":"2019","journal-title":"Herbalgram"},{"key":"e_1_2_10_3_1","unstructured":"Goldenseal \u2010 Hydrastis Canadensis.Health Canada<http:\/\/webprod.hc\u2010sc.gc.ca\/nhpid\u2010bdipsn\/monosReq.do%3Flang=eng> (2019). Accessed March 20 2020."},{"key":"e_1_2_10_4_1","first-page":"152","article-title":"Patient counseling about herbal\u2010drug interactions","volume":"8","author":"Hussain M.S.","year":"2011","journal-title":"African J. Tradit. Complement. Altern. Med."},{"key":"e_1_2_10_5_1","unstructured":"Goldenseal.National Center for Complementary and Integrative Health<https:\/\/www.nccih.nih.gov\/health\/goldenseal> (2016). 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Protoc. Toxicol."},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2019.03.027"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b19-00031"},{"key":"e_1_2_10_24_1","unstructured":"Guidance for Industry: In Vitro Drug Interaction Studies \u2014 Cytochrome P450 Enzyme\u2010 and Transporter\u2010Mediated Drug Interactions Guidance. FDA Guidance Document. (2020)."},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/00912709922008290"},{"key":"e_1_2_10_26_1","unstructured":"Guidance for Industry: Establishing Bioequivalence Guidance for Industry Statistical Approaches to Establishing Bioequivalence. FDA Guidance Document. 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