title: Enhancement effect of resveratrol on the intestinal absorption of bestatin by regulating PEPT1, MDR1 and MRP2 in vivo and in vitro.
abstract: The purpose of present study was to assess the enhancing effect of resveratrol (Res) on the absorption of bestatin and clarify the related molecular mechanism. Res facilitated bestatin absorption by down-regulating both protein and gene levels of multidrug resistance 1 (Mdr1) and Multidrug resistance-associated protein 2 (Mrp2), and up-regulating oligopeptide transporter 1 (Pept1) protein and mRNA expression in rat intestine. In the same manner, Res increased penetration of bestatin via significantly activating mRNA and protein expression of PEPT1 in Caco-2 cells. Conversely, mRNA and protein expression levels of MDR1, MRP2 and phosphorylation level of Insulin-like growth factor 1 receptor (IGF-1R) were inhibited by Res in Caco-2 cells. Moreover, Res also altered the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT). Res enhanced the intracellular concentration of bestatin by down-regulating MDR1 and MRP2 expression through a mechanism that involves IGF-1R/AKT/ERK signaling pathway inhibition in Caco-2 cells. In conclusion, Res enhances bestatin absorption by regulating PEPT1, MDR1 and MRP2 both in vivo and in vitro.
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China. Electronic address: yongmingjiahlj@126.com.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China. Electronic address: liuzhihao12399@126.com.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian 116044, China. Electronic address: huoxiaokui@163.com.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Huo
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian 116044, China. Electronic address: wangcyuan@163.com.
authors.forename: Changyuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian 116044, China. Electronic address: mengq531@yahoo.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian 116044, China. Electronic address: llaqii@yahoo.com.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian 116044, China. Electronic address: sunhuijun@hotmail.com.
authors.forename: Huijun
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China. Electronic address: spfar1004@gmail.com.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China. Electronic address: bocai789770@163.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China. Electronic address: xiaohong_shu@dlmedu.edu.cn.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Shu
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian 116044, China. Electronic address: kexinliu@dlmedu.edu.cn.
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000096:biosynthesis*; D000818:Animals; D018938:Caco-2 Cells; D015536:Down-Regulation; D006801:Humans; D007408:Intestinal Absorption; D007930:Leucine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D000074011:Peptide Transporter 1; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D027981:Symporters / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D064286:ATP Binding Cassette Transporter 1; D007930:Leucine; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074011:Peptide Transporter 1; D012333:RNA, Messenger; D017526:Receptor, IGF Type 1; D000077185:Resveratrol; D013267:Stilbenes; D027981:Symporters; C000715087:ABCC2 protein, human; C012211:ubenimex
keywords: Absorption; Bestatin; Insulin-like growth factor 1 receptor; Resveratrol; Transporter