title: Effects of anthocyans on the expression of organic anion transporting polypeptides (SLCOs/OATPs) in primary human hepatocytes.
abstract: Anthocyans (anthocyanins and their aglycones anthocyanidins) are colorful pigments, naturally occurring in fruits. They exhibit many biological effects and have potent health benefits. Anthocyans are widely used as dietary supplements and the safety of products containing them is of great importance. To investigate whether anthocyans influence the expression of hepatic uptake transporters from the organic anion transporting polypeptide (SLCO gene/OATP protein) family, we carried out studies on primary cultures of human hepatocytes. The hepato-cellular accumulation of widely used drugs such as statins and some anticancer drugs is mediated by the liver-specific OATP1B1 and OATP1B3, thus any interference with expression of these particular transporters might influence therapeutic outcomes. We evaluated the effects of 21 anthocyanins and their corresponding 6 anthocyanidins on the expression levels of SLCO1B1/SLCO1B3 by RT-qPCR. Changes in OATP protein levels were confirmed by western blotting. Our data show that OATP1B1 responds differently to anthocyans compared with OATP1B3. We observed the induction of SLCO1B1 gene and OATP1B1 protein in four hepatocyte samples by the anthocyanins malvin chloride, malvidin-3-O-galactoside chloride and cyanidin-3-O-sophoroside chloride. For SLCO1B3, a reduction in the expression levels was seen with delphin chloride and the anthocyanidin pelargonidin. Although the values varied considerably between primary hepatocyte isolates from different individuals, a mean induction of SLCO1B1 (up to 60%) and reduction of SLCO1B3 (by less than 25%) were detected. We propose that the effects of anthocyans derived from high dose dietary supplements may have to be taken into account in patients undergoing a therapy with drugs transported by OATP1B1 and OATP1B3.
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
authors.forename: Juliane
authors.initials: J
authors.lastname: Riha
authors.forename: Stefan
authors.initials: S
authors.lastname: Brenner
authors.forename: Alzbeta
authors.initials: A
authors.lastname: Srovnalova
authors.forename: Lukas
authors.initials: L
authors.lastname: Klameth
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Dvorak
authors.forename: Walter
authors.initials: W
authors.lastname: Jäger
authors.forename: Theresia
authors.initials: T
authors.lastname: Thalhammer
mesh_terms: D000328:Adult; D000872:Anthocyanins / Q000737:chemistry / Q000378:metabolism*; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D019587:Dietary Supplements; D005638:Fruit / Q000737:chemistry; D005697:Galactosides / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation; D005960:Glucosides / Q000737:chemistry / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D027361:Organic Anion Transporters / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
chemical_list: D000872:Anthocyanins; D016588:Anticarcinogenic Agents; D005697:Galactosides; D005960:Glucosides; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; C503999:SLCO1B1 protein, human; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; C066957:pelargonidin; C017154:cyanidin; C017185:delphinidin; C502603:malvin