Enhancement effect of resveratrol on the intestinal absorption of bestatin by regulating PEPT1, MDR1 and MRP2 in vivo and in vitro

被引：20

作者：

Jia, Yongming ^{[1
]}

Liu, Zhihao ^{[1
]}

Huo, Xiaokui ^{[1
,2
]}

Wang, Changyuan ^{[1
,2
]}

Meng, Qiang ^{[1
,2
]}

Liu, Qi ^{[1
,2
]}

Sun, Huijun ^{[1
,2
]}

Sun, Pengyuan ^{[1
]}

Yang, Xiaobo ^{[1
]}

Shu, Xiaohong ^{[1
]}

Liu, Kexin ^{[1
,2
]}

机构：

[1] Dalian Med Univ, Coll Pharm, Dept Clin Pharmacol, Dalian 116044, Peoples R China

[2] Dalian Med Univ, Prov Key Lab Pharmacokinet & Transport, Dalian 116044, Peoples R China

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2015年 / 495卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Resveratrol; Bestatin; Absorption; Insulin-like growth factor 1 receptor; Transporter; BREAST-CANCER CELLS; MULTIDRUG-RESISTANCE; TISSUE DISTRIBUTION; SIGNALING PATHWAYS; TRANSPORTER PEPT1; CACO-2; CELLS; DOXORUBICIN; ACTIVATION; INHIBITORS; EXPRESSION;

D O I：

10.1016/j.ijpharm.2015.09.042

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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. (C) 2015 Elsevier B.V. All rights reserved.

引用

页码：588 / 598

页数：11

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