title: Schisandrin A and B induce organic anion transporting polypeptide 1B1 transporter activity.
abstract: Organic anion transporting polypeptide 1B1 (OATP1B1) is the most important transporter in the organic anion transporting polypeptide family. OATP1B1 plays an important role in the hepatic uptake of many endogenous compounds and xenobiotics, including many clinical drugs. At present, the combinational usage of Chinese traditional herbal medicines and conventional chemical pharmaceuticals may affect the activity of enzymes and transporters activity and cause absorption of their substrates and metabolic changes. In this study, we aimed to investigate the effect of schisandrin A, schisandrin B and tanshinone IIA, which were extracted from medicinal plants, on OATP1B1 activity. HepG2 cells are used as in vitro models for OATP1B1 activity studies. A combination of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tertazolium bromide (MTT) assays, real-time RT-PCR, and transporter activity analysis were employed. We found that schisandrin A and B increased OATP1B1 mRNA levels by 1.81-fold (p < 0.01) and 1.87-fold (p < 0.01) at concentration of 10 μM, respectively. Schisandrin A of 1 μM and 10 μM and schisandrin B of 10 μM significantly increased the uptake of [3H] estrone-3-sulfate (p < 0.05 or p < 0.01). Tanshinone IIA had no effect on the mRNA expression and transport activity of OATP1B1 at nontoxic concentrations. Our study suggests that schisandrin A and B induced OATP1B1 expression and increased its transporter activity in HepG2 cells.
authors.forename: Cheng-Xian
authors.initials: CX
authors.lastname: Guo
authors.forename: Sheng
authors.initials: S
authors.lastname: Deng
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Yin
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D045784:Abietanes / Q000494:pharmacology; D045744:Cell Line, Tumor; D034242:Cyclooctanes / Q000494:pharmacology*; D004970:Estrone / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters / Q000096:biosynthesis* / Q000235:genetics; D010946:Plants, Medicinal / Q000737:chemistry; D011083:Polycyclic Compounds / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D045784:Abietanes; D034242:Cyclooctanes; D017705:Lignans; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D011083:Polycyclic Compounds; D012333:RNA, Messenger; C503999:SLCO1B1 protein, human; C015499:schizandrin B; C021751:tanshinone; D004970:Estrone; C034734:schizandrin A; C017296:estrone sulfate