Proanthocyanidin-Rich Grape Seed Extract Reduces Inflammation and Oxidative Stress and Restores Tight Junction Barrier Function in Caco-2 Colon Cells.

Rameshprabu Nallathambi,Alexander Poulev,Joshua B Zuk,Ilya Raskin

doi:10.3390/nu12061623

Rameshprabu Nallathambi, Alexander Poulev + Show 2 more

Open Access

https://doi.org/10.3390/nu12061623

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Journal: Nutrients	Publication Date: Jun 1, 2020
Citations: 66	License type: CC BY 4.0

Affiliation: Rutgers, The State University of New Jersey

Abstract

Grape polyphenols have previously been shown to improve gut health and attenuate the symptoms of metabolic syndrome; however, the mechanism of these beneficial effects is still debated. In this study, we investigated the protective effect of proanthocyanidin-rich grape seed extract (GSE) on bacterial lipopolysaccharide (LPS)-induced oxidative stress, inflammation, and barrier integrity of human Caco-2 colon cells. GSE significantly reduced the LPS-induced intracellular reactive oxygen species (ROS) production and mitochondrial superoxide production, and upregulated the expression of antioxidant enzyme genes. GSE also restored the LPS-damaged mitochondrial function by increasing mitochondrial membrane potential. In addition, GSE increased the expression of tight junction proteins in the LPS-treated Caco-2 cells, increased the expression of anti-inflammatory cytokines, and decreased pro-inflammatory cytokine gene expression. Our findings suggest that GSE exerts its beneficial effects on metabolic syndrome by scavenging intestinal ROS, thus reducing oxidative stress, increasing epithelial barrier integrity, and decreasing intestinal inflammation.

Highlights

Reactive oxygen species (ROS) play an important role in pathological processes in the gastrointestinal (GI) tract including diabetes, Crohn’s disease, ulcerative colitis, and colon cancer [1,2].Prolonged exposure of the intestine to ROS leads to oxidative stress, lipid peroxidation, protein degradation, and damage to macromolecules [1,2,3,4,5]
In order to understand the relationship between grape seed extract (GSE) antioxidants and LPS-induced oxidative stress, we examined the effect of GSE on mitochondrial dysfunction, intracellular ROS, and mitochondrial superoxide production on LPS-treated differentiated Caco-2 cells (Figure 2)
To confirm the above observations, we examined the ability of GSE to counteract the effects of LPS on the content of the transmembrane tight junction proteins zona occludens 1 (ZO1), occludin, and claudin 1 in Caco-2 monolayer with immunocytochemistry (Figure 5A–C)

Summary

Introduction

Reactive oxygen species (ROS) play an important role in pathological processes in the gastrointestinal (GI) tract including diabetes, Crohn’s disease, ulcerative colitis, and colon cancer [1,2].Prolonged exposure of the intestine to ROS leads to oxidative stress, lipid peroxidation, protein degradation, and damage to macromolecules [1,2,3,4,5]. The nuclear factor kappa B (NF-κB) cascade activated by ROS leads to the production of pro-inflammatory molecules, including cytokines and chemokines that may contribute to insulin resistance [3,4,5]. The high-fat diet elicits an inflammatory response by inducing pro-inflammatory cytokines and insulin resistance and by increasing uric acid and thiol group production, resulting from the antioxidant response triggered by ROS [3,7,8]. The high-fat diet increases whole-body inflammation and insulin resistance, which leads to metabolic syndrome and may be mediated by the gut microbiome [9]. The high-fat diet was shown to increase the proportion of Gram-negative species in the gut, contributing to the increased production and absorption of pro-inflammatory bacterial lipopolysaccharides (LPS), leading to a low-grade metabolic endotoxemia [10]. The interaction of circulating LPS with TLR-4/CD-14 receptors may trigger an Nutrients 2020, 12, 1623; doi:10.3390/nu12061623 www.mdpi.com/journal/nutrients

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