Scutellarin inhibition of the rosuvastatin uptake in rat hepatocytes and the competition for organic anion transporting polypeptide 1B1 in HEK293T cells.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Anions/*metabolism ; Apigenin/*pharmacology ; Glucuronates/*pharmacology ; Hepatocytes/*drug effects ; Hepatocytes/*metabolism ; Liver-Specific Organic Anion Transporter 1/*metabolism ; Rosuvastatin Calcium/*metabolism; Animals ; Biomarkers ; Cell Line, Tumor ; Gene Expression ; Humans ; Liver/drug effects ; Liver/metabolism ; Liver-Specific Organic Anion Transporter 1/genetics ; Male ; Mass Spectrometry ; Rats ; Rosuvastatin Calcium/blood

In this report, we investigated the hepatocytic uptake of rosuvastatin when administered with scutellarin (a Chinese herbal medicine) in rats and the role of organic anion transporting polypeptide 1B1 (OATP1B1) plays in the uptake. Forty-eight rats were randomly divided into two groups according to the medicine administered: rosuvastatin alone and rosuvastatin in combination with a series concentration of scutellarin. Rosuvastatin concentrations in blood and liver were measured using the liquid chromatography-tandem mass spectrometry (LC-MS) method. The uptake was also measured in rat primary hepatocytes and OATP1B1 transfected human embryonic kidney 293 T (HEK293T) cells. The uptake was investigated under the optimal intake conditions. The rosuvastatin Cmax and AUC 0-∞ in rat plasma increased 55% and 61%, respectively in the combination treatment group; and the liver scutellarin concentrations decreased 32%, 34%, and 33% at 1 h, 2 h, and 6 h, respectively. All scutellarin dosages (20, 50, and 100 μM) inhibited the uptake of rosuvastatin in rat primary hepatocytes (4.71%, 22.73%, and 45.89%). Scutellarin of 10 μM significantly inhibited the in vitro uptake of rosuvastatin in OATP1B1-HEK293T cells (P < 0.05), with an IC50 of 60.53 ± 5.74 μM. Scutellarin increases the plasma concentration of rosuvastatin and inhibits the uptake in rat primary hepatocytes and OATP1B1-HEK293T cells, suggesting a drug interaction between scutellarin and rosuvastatin and OATP1B1 as a potential mechanism.

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0 (Anions)
0 (Biomarkers)
0 (Glucuronates)
0 (Liver-Specific Organic Anion Transporter 1)
0 (SLCO1B1 protein, human)
16IGP0ML9A (scutellarin)
7V515PI7F6 (Apigenin)
83MVU38M7Q (Rosuvastatin Calcium)

Date Created: 20200130 Date Completed: 20200610 Latest Revision: 20210127

20231215

PMC6987161

10.1038/s41598-020-58303-0

31992796