Journal Article

Daidzein Protects Caco-2 Cells against Lipopolysaccharide-Induced Intestinal Epithelial Barrier Injury by Suppressing PI3K/AKT and P38 Pathways

Tan, Xiaomei, Ding, Mengze, Wei, Xiaohan, Zhang, Baoping, Zheng, Zezhong, Luo, Zhenye

2022

Overview

The intestinal epithelium provides an important barrier against bacterial endotoxin translocation, which can regulate the absorption of water and ions. The disruption of epithelial barrier function can result in water transport and tight junction damage, or further cause diarrhea. Therefore, reducing intestinal epithelial barrier injury plays an important role in diarrhea. Inflammatory response is an important cause of intestinal barrier defects. Daidzein improving the barrier integrity has been reported, but the effect on tight junction proteins and aquaporins is not well-described yet, and the underlying mechanism remains indistinct in the human intestinal epithelium. This study aimed to investigate the effects and mechanisms of daidzein on intestinal epithelial barrier injury induced by LPS, and a barrier injury model induced by LPS was established with human colorectal epithelial adenocarcinoma cell line Caco-2 cells. We found that daidzein protected the integrity of Caco-2 cell monolayers, reversed LPS-induced downregulation of ZO-1, occludin, claudin-1, and AQP3 expression, maintained intercellular junction of ZO-1, and suppressed NF-κB and the expression of inflammatory factors (TNF-α, IL-6). Furthermore, we found that daidzein suppressed the phosphorylation of the PI3K/AKT and P38 pathway-related proteins and the level of the related genes, and the PI3K/AKT and P38 pathway inhibitors increased ZO-1, occludin, claudin-1, and AQP3 expression. The study showed that daidzein could resist LPS-induced intestinal epithelial barrier injury, and the mechanism is related to suppressing the PI3K/AKT and P38 pathways. Therefore, daidzein could be a candidate as a dietary supplementation or drug to prevent or cure diarrhea.

• Publisher: MDPI AG,MDPI
• Subject: AQP3 / Aquaporins / Caco-2 Cells / Claudin-1 / Cytotoxicity / daidzein / Diarrhea / Diarrhea - metabolism / Dietary supplements / Epithelial Cells / Gene expression / Homeostasis / Humans / intestinal epithelial barrier injury / Intestinal Mucosa - metabolism / Isoflavones / Lipopolysaccharides - metabolism / Lipopolysaccharides - toxicity / Occludin - metabolism / P38 / Phosphatidylinositol 3-Kinases - metabolism / Phosphorylation / PI3K/AKT / Protein expression / Proteins / Proto-Oncogene Proteins c-akt - metabolism / Tight Junction Proteins - metabolism / Tight Junctions - metabolism / Tumor necrosis factor-TNF