title: Transport characteristics of isorhamnetin across intestinal Caco-2 cell monolayers and the effects of transporters on it.
abstract: Flavonoid isorhamnetin occurs in various plants and herbs, and demonstrates various biological effects in humans. This work will clarify the isorhamnetin absorption mechanism using the Caco-2 monolayer cell model. The isorhamnetin transport characteristics at different concentrations, pHs, temperatures, tight junctions and potential transporters were systemically investigated. Isorhamnetin was poorly absorbed by both passive diffusion and active transport mechanisms. Both trans- and paracellular pathways were involved during isorhamnetin transport. Active transport under an ATP-dependent transport mechanism was mediated by the organic anion transporting peptide (OATP); isorhamnetin's permeability from the apical to the basolateral side significantly decreased after estrone-3-sulfate was added (p<0.01). Efflux transporters, P-glycoproteins (P-gp), breast cancer resistance proteins (BCRP) and multidrug resistance proteins (MRPs) participated in the isorhamnetin transport process. Among them, the MRPs (especially MRP2) were the main efflux transporters for isorhamnetin; transport from the apical to the basolateral side increased 10.8-fold after adding an MRP inhibitor (MK571). This study details isorhamnetin's cellular transport and elaborates isorhamnetin's absorption mechanisms to provide a foundation for further studies.
authors: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Jingze
authors: J
authors: Duan
authors: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: rosexie_1996@hotmail.com.
authors: Yan
authors: Y
authors: Xie
authors: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Experiment Center of Teaching & Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Huilin
authors: H
authors: Luo
authors: Pharmacy Department, Shanghai TCM-integrated Hospital, Shanghai 200082, China. Electronic address: lgwshutcm@163.com.
authors: Guowen
authors: G
authors: Li
authors: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Tao
authors: T
authors: Wu
authors: Experiment Center of Teaching & Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Tong
authors: T
authors: Zhang
mesh_terms: D018938:Caco-2 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000378:metabolism; D013696:Temperature
chemical_list: D026901:Membrane Transport Proteins; C047368:3-methylquercetin; D011794:Quercetin
keywords: Absorption mechanism; Caco-2 cell; Isorhamnetin; Transport; Transporters