{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T20:48:24Z","timestamp":1777668504978,"version":"3.51.4"},"reference-count":24,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["8157141040"],"award-info":[{"award-number":["8157141040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:p>\n                    The Na\n                    <jats:sup>+<\/jats:sup>\n                    -taurocholate cotransporting polypeptide (NTCP) acts as the major hepatic basolateral uptake system, and plays a key role in balancing bile flow. The anti-tuberculosis drugs rifampin (RFP) can affect bile flow causing liver injury, while tanshinone IIA (TAN IIA) has the effect of protecting liver. This study aimed to investigate the effects of RFP and TAN IIA on the NTCP expression and activity, and explore the potential connections. Herein, we established sandwich-cultured primary rat hepatocytes, and quantified mRNA and protein levels of NRF2 and NTCP after treatment with RFP (10, 25, or 50 \u03bcM) or co-treatment with TAN IIA (5, 10, or 20 \u03bcM) for 12, 24, 48 h (n = 3). NTCP activity was assessed by measuring the initial uptake rates of known substrates taurocholate (TCA) (n = 3) after treatment with different concentrations of RFP, TAN \u2161A for 12, 24 and 48 h. We found that RFP had inhibition effects on NRF2, NTCP mRNA and protein expression, and co-administration of TAN IIA could reverse RFP inhibition. TCA cellular accumulation was significantly decreased by RFP (39.1%), and TAN IIA could significantly induce TCA uptake of NTCP (2.9-fold at 48 h). The TCA uptake activity was correlated with the NTCP mRNA expression, confirming the role of RFP or TAN IIA on NTCP expression and activity is synchronous, and we can predict NTCP activity by detecting its mRNA expression. In conclusion, our work will enrich the significance of NTCP in the liver protection, and provide theoretical basis for TAN IIA to prevent RFP induced cholestatic liver injury.\n                  <\/jats:p>","DOI":"10.1177\/0960327120979030","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T10:31:06Z","timestamp":1607941866000},"page":"1003-1011","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Tanshinone \u2161A may alleviate rifampin-induced cholestasis by regulating the expression and function of NTCP"],"prefix":"10.1177","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6941-0380","authenticated-orcid":false,"given":"Y","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The Third People\u2019s Hospital of Chengdu, College of Medicine, Southwest Jiaotong University, Chengdu, China"},{"name":"Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, China"},{"name":"Department of Pharmacy, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, 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