title: Polyphenol-Rich Propolis Extracts Strengthen Intestinal Barrier Function by Activating AMPK and ERK Signaling.
abstract: Propolis has abundant polyphenolic constituents and is used widely as a health/functional food. Here, we investigated the effects of polyphenol-rich propolis extracts (PPE) on intestinal barrier function in human intestinal epithelial Caco-2 cells, as well as in rats. In Caco-2 cells, PPE increased transepithelial electrical resistance and decreased lucifer yellow flux. PPE-treated cells showed increased expression of the tight junction (TJ) loci occludin and zona occludens (ZO)-1. Confocal microscopy showed organized expressions in proteins related to TJ assembly, i.e., occludin and ZO-1, in response to PPE. Furthermore, PPE led to the activation of AMPK, ERK1/2, p38, and Akt. Using selective inhibitors, we found that the positive effects of PPE on barrier function were abolished in cells in which AMPK and ERK1/2 signaling were inhibited. Moreover, rats fed a diet supplemented with PPE (0.3% in the diet) exhibited increased colonic epithelium ZO-1 expression. Overall, these data suggest that PPE strengthens intestinal barrier function by activating AMPK and ERK signaling and provide novel insights into the potential application of propolis for human gut health.
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. kaiwang628@gmail.com.|CSIRO Food and Nutrition, Adelaide 5000, Australia. kaiwang628@gmail.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. chnfhjxl@163.com.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Jin
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. cgxllx@163.com.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. zehesong@gmail.com.
authors.forename: Zehe
authors.initials: Z
authors.lastname: Song
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. xiasenjiang@163.com.
authors.forename: Xiasen
authors.initials: X
authors.lastname: Jiang
authors.affiliation: College of Animal Sciences, Zhejiang University, Hangzhou 310058, China. flhu@zju.edu.cn.
authors.forename: Fuliang
authors.initials: F
authors.lastname: Hu
authors.affiliation: CSIRO Food and Nutrition, Adelaide 5000, Australia. michael.conlon@csiro.au.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Conlon
authors.affiliation: CSIRO Food and Nutrition, Adelaide 5000, Australia. david.topping@csiro.au.
authors.forename: David L
authors.initials: DL
authors.lastname: Topping
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018938:Caco-2 Cells; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects; D007422:Intestines / Q000187:drug effects* / Q000502:physiology; D010539:Permeability; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D011429:Propolis / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D059808:Polyphenols; D011429:Propolis; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Caco-2; ERK; propolis; tight junctions