title: Interaction of the bioactive flavonol, icariin, with the essential human solute carrier transporters.
abstract: Solute carrier transporters (SLCs), in particular the organic anion transporting polypeptides (OATPs) and organic anion/cation transporters (OATs/OCTs), are responsible for the cellular entry of many clinically important drugs in body. They largely influence drug safety and efficacy. Icariin is a flavonol widely present in many herbal preparations, which is used to improve sexual function and prevent osteogenesis. However, precautions are necessary in therapies containing icariin due to its involvement in drug-drug/herb interactions, possibly mediated through competing drug uptake via membrane-transporter proteins. This study is the first to comprehensively evaluate the interactions between icariin and a range of essential SLCs. Our data demonstrated that icariin can significantly inhibit OATP1B3- and OATP2B1-mediated cellular uptake of specific substrates (IC₅₀ of 3.0 ± 1.3 and 6.4 ± 1.9 μM, respectively). Our study revealed that icariin can potentially compete with coadministrated drugs for particular SLCs, which may impact the therapeutic outcome of regimens.
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, New SouthWales, Australia.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Florence Shin Gee
authors.initials: FS
authors.lastname: Cheung
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.forename: Ting
authors.initials: T
authors.lastname: Chan
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
authors.forename: Fanfan
authors.initials: F
authors.lastname: Zhou
mesh_terms: D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
chemical_list: D005419:Flavonoids; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; C421209:SLCO1B3 protein, human; C450859:SLCO2B1 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; C056599:icariin
keywords: Icariin; OATP1B3; OATP2B1; Solute Carrier Transporters