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.
Highlights
Propolis is a plant-derived substance collected by honeybees (Apis mellifera L.) from various sources [1]
To evaluate the effects of propolis extracts (PPE) on intestinal epithelial tight junctions (TJ) permeability, Transepithelial electrical resistance (TER) and lucifer yellow (LY) flux were measured in Caco-2 cell monolayers
An intermediate concentration of PPE had a moderate effect on epithelial TJ permeability; 24 h treatment led to a 20.1% increase in TER (Figure 1A)
Summary
Propolis is a plant-derived substance collected by honeybees (Apis mellifera L.) from various sources [1]. Mainly flavonoids and phenolic acids, have been identified in propolis [2]. It has well-documented pharmacological activities, including antimicrobial, antioxidant, anti-inflammatory, immunomodulatory, and cardioprotective effects, and it is used widely as a health/functional food worldwide [3]. The intestinal mucosal barrier mainly consists of intestinal epithelial cells (IECs) on the luminal side and tight junctions (TJ) between IECs [4]. This barrier allows the transcellular transport of essential nutrients and controls the diffusion of luminal macromolecules and bacteria across the gut mucosa. Recent studies suggest that increasing intestinal barrier integrity has great therapeutic potential in IBD treatment [4,6]
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