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

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• 作者：Yongming Jia^a ; ¹ ; ^{yongmingjiahlj@126.com" class="auth_mail" title="E-mail the corresponding author} ; Zhihao Liu^a ; ¹ ; ^{liuzhihao12399@126.com" class="auth_mail" title="E-mail the corresponding author} ; Xiaokui Huo^a ; ^b ; ^{huoxiaokui@163.com" class="auth_mail" title="E-mail the corresponding author} ; Changyuan Wang^a ; ^b ; ^{wangcyuan@163.com" class="auth_mail" title="E-mail the corresponding author} ; Qiang Meng^a ; ^b ; ^{mengq531@yahoo.cn" class="auth_mail" title="E-mail the corresponding author} ; Qi Liu^a ; ^b ; ^{llaqii@yahoo.com.cn" class="auth_mail" title="E-mail the corresponding author} ; Huijun Sun^a ; ^b ; ^{sunhuijun@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; Pengyuan Sun^a ; ^{spfar1004@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Xiaobo Yang^a ; ^{bocai789770@163.com" class="auth_mail" title="E-mail the corresponding author} ; Xiaohong Shu^a ; ^{xiaohong_shu@dlmedu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Kexin Liu^a ; ^b ; ^{kexinliu@dlmedu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Res ; resveratrol ; Mdr1 ; multidrug resistance 1 ; Pept1 ; peptide transporter 1 ; Mrp2 ; multidrug resistance-associated protein 2 ; IGF-1R ; insulin-like growth factor 1 receptor ; ERK ; extracellular signal-regulated kinase ; AKT ; protein kinase B ; ABC ; ATP-binding cassette ; SLC ; solute carrier ; P-gp ; P-glycoprotein ; Nrf2 ; nuclear factor 2 ; OCTs ; organic cation transporters ; OATs ; organic anion transporters ; Gly-Sar ; glycylsarcosine ; MTX ; methotrexate ; T3 ; triiodothyronine ; GNT ; genistein ; Rif ; rifampic
• 刊名：International Journal of Pharmaceutics
• 出版年：2015
• 出版时间：10 November 2015
• 年：2015
• 卷：495
• 期：1
• 页码：588-598
• 全文大小：2984 K

文摘

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.