Objective To study the inhibition of berberine on organ anion transporters (OATs) and its bidirectional trans-membrane transport.Method The transgene cell lines of the organ anion transporters including OAT1,OAT2,OAT3,OAT4,OAT7,and URAT1 were constructed and selected by animal cell transgenic method mediated by transporter Lipo 3000.Wild type (WT) cells were used as control group,and activity of OATs was verified by adding their radiolabeled substrates and inhibitors.The inhibition of 100 μmol/L berberine on the transporters was investigated in vitro.The IC50 of berberine on URAT1 was also determined.The bidirectional transport of berberine was studied through the Caco-2 model.Result The results showed that 100 μmol/L berberine inhibited the activity of OAT1,OAT2,OAT3,OAT4,OAT7 and URAT1 to (70.48±4.23)％,(69.13±1.28)％,(72.12±3.28)％,(79.77±6.49)％,(69.51 ±5.99)％ and (38.4 ± 2.67)％ respectively,the IC50 of berberine to URAT 1 was 13.19 μmol/L,the Papp (A-B) of 50 μmol/L and 100 μmol/L berberine were separately 0.28 × 10-6 and 0.40 × 10-6 cm/s,and the effiux rates were separately 3.18 and 3.15.Conclusion Berberine shows a stronger inhibition to URAT1 compared to OAT1,OAT2,OAT3,OAT4 and OAT7.Berberine may be the substrate of some effiux transporters.This study provides theoretical basis for explaining the low bioavailability ofberberine and forecasting the possible drug-drug interaction.

Objective To study the inhibitory effects ofberberine on human organic cation transporter (OCTs) including OCT1,OCT2,OCT3,OCTN1 and OCTN2.Methods Using animal cell transgenic method mediated by transporter Lipo 3000,the drug transporters over expression cell lines S2-OCT1,S2-OCT2,S2-OCT3,S2-OCTN1 and S2-OCTN2 were obtained by selective medium culture.The OCTs evaluation model was established by detecting the trans-membrane transport of radioactive substrate in vitro.Wild type (WT) cells were used as control group,activity of OCTs was verified by adding its inhibitor.The inhibition of berberine on the transporters was investigated in vitro.The IC50 of inhibitory effect of berberine on various drug transporters was also calculated.Result The transport activity of transporter cell lines was increased by more than 5 times compared to the WT cell line respectively,what's more,their transport activity decreased significantly by their corresponding inhibitor.The ICs0 of berberine to OCT1,OCT2,OCT3,OCTN1 and OCTN2 were respectively 7.63,6.80,2.25,4.66 and 210.34 μmol/L.Conclusion Berberine significant inhibition to OCT1,OCT2,OCT3,OCTN1 and OCTN2.The inhibition on OCT1,OCT2,OCT3,OCTN1 is stronger compared to OCTN2.

OBJECTIVE：To investigate the potential mechanism of Salvia miltiorrhiza in the treatment of postoperative abdominal adhesion （PAA）. METHODS ：Active components and target genes of S. miltiorrhiza were retrieved from TCMSP database，SwissADME database ，Perl database ，UniProt database and other databases. GeneCards ，OMIM and PubMed database were used to retrieve target genes related to PAA. Venn diagram was drawn by using mapping tool of bioinformatic online database so as to screen the intersecting targets of active component-PAA. STRING platform was adopted to establish target network related to active component-PAA and protein-protein interaction （PPI）network of intersecting targets ，etc.，and to screen hub genes. Gene ontology（GO）and Kyoto Encyclopedia of Genes and Genom es（KEGG）pathway enrichment were carried out by using R 3.6.1 software. Using the protein encoded by hub gene as receptor and tanshinone Ⅱ A as ligand ，the molecular docking was carried out with AutoDock 1.5.6 tool. RESULTS ：A total of 38 active components of S. miltiorrhiza with high gastrointestinal absorption and their corresponding 72 targets，755 PAA-related target genes were identified. Results of Venn diagram showed that there were 33 intersecting targets of active components of chuqi90@163.com S. miltiorrhiza with PAA. Tanshinone ⅡA，dihydrotanshinolac- tone and other components may be important nodes of the target network related to active component-PAA. FOS，APP，ACHE， CASP3 and PTGS2 may be the hub genes in PPI network of intersecting targets. Results of GO enrichment showed that the intersecting targets were mainly concentrated in adrenergic receptor activity ，catecholamine binding ，G protein-coupled amine receptor activity and so on ；KEGG pathway enrichment analysis showed that the intersecting targets were mainly enriched in neuroactive ligand-receptor interaction ，cGMP-PKG signaling pathway ，endocrine resistance ，EGFR-tyrosine kinase inhibitor resistance and calcium signaling pathway.Molecular docking analysis showed that tanshinone ⅡA could form hydrogen bonds with many amino acid residues such as VAL- 580 of proto oncogenes c-Fos ，amyloid precursor protein ，acetylcholinesterase，caspase 3 and prostaglandin G/H synthase 2. CONCLUSIONS ：The active components of S. miltiorrhiza play a role in the treatment of PAA by directly or indirectly acting on neuroactive ligand-receptor interaction ，cGMP-PKG signaling pathway ，endocrine resistance ， EGFR-tyrosine kinase inhibitor resistance resistance and calcium signaling pathway.