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Hepatic organic anion transporting polypeptides mediate disposition of milk thistle flavonolignans and pharmacokinetic silymarin-drug interactions
- Source :
- Phytother Res
- Publication Year :
- 2020
-
Abstract
- Silybum marianum (L.) Gaertn. (Asteraceae), commonly known as milk thistle, is a botanical natural product used to self-treat multiple diseases such as type 2 diabetes mellitus and nonalcoholic steatohepatitis (NASH). An extract from milk thistle seeds (achenes), termed silymarin, is comprised primarily of several flavonolignans. Systemic concentrations of these flavonolignans can influence the potential biologic effects of silymarin and the risk for pharmacokinetic silymarin-drug interactions. The aims of this research were to determine the roles of organic anion transporting polypeptides (OATPs/Oatps) in silymarin flavonolignan disposition and in pharmacokinetic silymarin-drug interactions. The seven major flavonolignans from silymarin were determined to be substrates for OATP1B1, OATP1B3, and OATP2B1. Sprague Dawley rats were fed either a control diet or a NASH-inducing diet and administered pitavastatin (OATP/Oatp probe substrate), followed by silymarin via oral gavage. Decreased protein expression of Oatp1b2 and Oatp1a4 in NASH animals increased flavonolignan area under the plasma concentration-time curve (AUC) and maximum plasma concentration. The combination of silymarin inhibition of OATPs/Oatps and NASH-associated decrease in Oatp expression caused an additive increase in plasma pitavastatin AUC in the animals. These data indicate that OATPs/Oatps contribute to flavonolignan cellular uptake and mediate the interaction between silymarin and NASH on pitavastatin systemic exposure.
- Subjects :
- Male
Organic Anion Transporters
Pharmacology
Antioxidants
Article
Silybum marianum
Flavonolignans
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Pharmacokinetics
Non-alcoholic Fatty Liver Disease
Flavonolignan
medicine
Animals
Humans
Milk Thistle
Drug Interactions
Pitavastatin
Flavonoids
0303 health sciences
Natural product
biology
030302 biochemistry & molecular biology
biology.organism_classification
Rats
Organic anion-transporting polypeptide
chemistry
030220 oncology & carcinogenesis
biology.protein
Quinolines
medicine.drug
Silymarin
Subjects
Details
- ISSN :
- 10991573
- Volume :
- 35
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Phytotherapy research : PTR
- Accession number :
- edsair.doi.dedup.....dbf994e2774b04dc89a96152f445a830