title: [Transport of limonin in rat intestine in situ and Caco-2 cells in vitro].
abstract: Limonin existed in citrus fruits has been shown to have anti-bacterial, anti-viral, anti-feedant, anti-nociceptive, anti-inflammatory activities and anti-carcinogenic activities. But the clinical use is limited by its low bioavailability. The aim of this study is to observe the absorption and secretion transport mechanisms of limonin in intestine which can pave the way for the further study and clinical use. The transport characteristics and mechanisms of limonin in rat were studied by in situ intestine perfusion and in vitro Caco-2 cells method. The intestinal absorption of limonin was probably via a facilitated diffusion pathway which was poor and without segment-selection. Verapamil and ketoconazole improved the absorption remarkably according to the result of in vitro Caco-2 cells study; however, probenecid had no significant effect on the absorption. The P-gp efflux and CYP3A4 metabolism were involved in the poor intestinal absorption and low bioavailability of limonin. The exploration of the intestinal absorption mechanism is crucial to the design of dosage form and clinical use of limonin.
authors.affiliation: Xiajin People's Hospital, Xiajin 253200, China.
authors.forename: Xiu-Yun
authors.initials: XY
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Ke
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.forename: Ji-Lai
authors.initials: JL
authors.lastname: Tian
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007654:Ketoconazole / Q000494:pharmacology; D036701:Limonins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D010477:Perfusion; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D036701:Limonins; D014700:Verapamil; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C001546:limonin; D011339:Probenecid; D007654:Ketoconazole