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Hepatic Uptake Mechanism of Ophiopogonin D Mediated by Organic Anion Transporting Polypeptides.
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- Author(s): Zhang W;Zhang W;Zhang W; Xiong X; Xiong X; Chen L; Chen L; Liu M; Liu M; Xiong Y; Xiong Y; Zhang H; Zhang H; Huang S; Huang S; Xia C; Xia C
- Source:
European journal of drug metabolism and pharmacokinetics [Eur J Drug Metab Pharmacokinet] 2017 Aug; Vol. 42 (4), pp. 669-676.- Publication Type:
Journal Article- Language:
English - Source:
- Additional Information
- Source: Publisher: Springer France Country of Publication: France NLM ID: 7608491 Publication Model: Print Cited Medium: Internet ISSN: 2107-0180 (Electronic) Linking ISSN: 03787966 NLM ISO Abbreviation: Eur J Drug Metab Pharmacokinet Subsets: MEDLINE
- Publication Information: Publication: <2010- >: Paris : Springer France
Original Publication: Paris, Edifor. - Subject Terms: Hepatocytes/*metabolism ; Liver/*metabolism ; Liver-Specific Organic Anion Transporter 1/*metabolism ; Saponins/*pharmacokinetics ; Solute Carrier Organic Anion Transporter Family Member 1B3/*metabolism ; Spirostans/*pharmacokinetics; Animals ; Dose-Response Relationship, Drug ; HEK293 Cells ; Humans ; Kinetics ; Liver-Specific Organic Anion Transporter 1/antagonists & inhibitors ; Liver-Specific Organic Anion Transporter 1/genetics ; Male ; Primary Cell Culture ; Rats, Sprague-Dawley ; Solute Carrier Organic Anion Transporter Family Member 1B3/antagonists & inhibitors
- Abstract: Background and Objectives: Ophiopogonin D (OPD) is one of the main active ingredients of SMI (Shenmai injection) which is widely used in clinical practice in China. Our previous study indicated that OPD might be transported from blood into liver mediated by organic anion transporting polypeptides (OATPs/oatps). This study aims to explore the hepatic uptake mechanism of OPD in rat and human.
Methods: Rosuvastatin (a competitive inhibitor of oatp1b2, oatp1a1, and oatp1a4), glycyrrhizic acid (a specific inhibitor of oatp1b2), digoxin (a specific inhibitor of oatp1a4), bromosulfophthalein (BSP), and ibuprofen (a specific inhibitor of oatp1a1) were used to study the uptake of OPD in rat hepatocytes. Furthermore, the uptake of OPD in human OATP1B1*1a-HEK293T cells was also investigated, and rosuvastatin, BSP, rifampin, and glycyrrhizic acid were all used as the competitive inhibitor of OATP1B1.
Results: OPD can be taken in rat primary hepatocytes with Km (Michaelis Menten constant) of 8.10 μM and Vmax (maximum velocity) of 54.39 nmol/min/mg protein. The uptake of OPD in rat hepatocytes was inhibited significantly by rosuvastatin and glycyrrhizic acid. However, digoxin, BSP, and ibuprofen had no effect on the uptake of OPD in rat hepatocytes. OPD can also be transported by OATP1B1*1a-HEK293T cells with Km of 5.50 μΜ and Vmax of 29.07 nmol/min/mg protein. Compared with rosuvastatin, OPD has a higher affinity with OATP1B1 and can be transported faster in unit time. Rosuvastatin, BSP, rifampin, and glycyrrhizic acid all exhibited a certain extent inhibitory effect on the transport of OPD in OATP1B1*1a-HEK293T cells.
Conclusions: Overall, this study indicates OATP1B1 in human and oatp1b2 in rats might participate in the hepatic uptake of OPD. - References: Biochem Pharmacol. 2010 Dec 1;80(11):1746-53. (PMID: 20797388)
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J Biotechnol. 1991 Jun;19(1):35-47. (PMID: 1369310) - Accession Number: 0 (Liver-Specific Organic Anion Transporter 1)
0 (SLCO1B1 protein, human)
0 (Saponins)
0 (Slco1b2 protein, rat)
0 (Solute Carrier Organic Anion Transporter Family Member 1B3)
0 (Spirostans)
41753-55-3 (ophiopogonin D) - Publication Date: Date Created: 20161106 Date Completed: 20180515 Latest Revision: 20181202
- Publication Date: 20221213
- Accession Number: 10.1007/s13318-016-0384-8
- Accession Number: 27815731
- Source:
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