{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:54:53Z","timestamp":1792007693068,"version":"4.4.0"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31460246"],"award-info":[{"award-number":["31460246"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Saikosaponin\u2010d (SSd) is a major bioactive triterpenoid saponin extracted from<jats:italic>Bupleurum<\/jats:italic>, which has anti\u2010inflammatory, anticancer, antioxidative and anti\u2010hepatic fibrosis effects. Due to the effects of<jats:italic>Bupleurum<\/jats:italic>\u2010related formulations on cytochrome P450 (CYPs) expression still remain unclear, the combination therapies involved formulations containing<jats:italic>Bupleurum<\/jats:italic>may sometimes lead to unexpected drug\u2010drug interactions in clinical practice. These interactions can limit the clinical applications of related formulations. In this study, we tried to explore the effects of SSd on CYP3A4 mRNA, protein expression and the enzyme activity in HepaRG cells by real\u2010time quantitative reverse transcription polymerase chain reaction (RT\u2010qPCR), Western blot (WB) and HPLC method, respectively. The interaction between SSd and CYP3A4 was analysed by molecular docking. HepaRG cells were cultured with different concentrations of SSd (0.5, 1, 5 and 10\u00a0\u03bcmol\/L) for 72\u00a0hours. It is revealed that SSd can inhibit CYP3A4 mRNA and its protein expression, and also the enzyme activity. Molecular\u00a0docking\u00a0study demonstrated that SSd can bind to several key active sites of amino acid residues of CYP3A4 protein with hydrogen bonds and hydrophobic interactions. Thus, drug\u2010drug interactions resulted by SSd inhibiting CYP3A4 need attention when formulations containing SSd or<jats:italic>Bupleurum<\/jats:italic>are co\u2010administrated with drugs metabolized by CYP3A4.<\/jats:p>","DOI":"10.1111\/bcpt.13552","type":"journal-article","created":{"date-parts":[[2020,12,26]],"date-time":"2020-12-26T10:04:01Z","timestamp":1608977041000},"page":"661-668","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Effects of saikosaponin\u2010d on CYP3A4 in HepaRG cell and protein\u2010ligand docking study"],"prefix":"10.1111","volume":"128","author":[{"given":"Hongfang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Clinical Pharamcy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy Zunyi Medical University Zunyi China"},{"name":"Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research 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