# Lactiplantibacillus plantarum WB3801 and Lactiplantibacillus plantarum WB3808 Showed Antioxidant Effect and Anti-Apoptosis through Activation of the Keap1/Nrf2/HO-1 Pathway in H2O2-Induced HT-29 Cells

## TL;DR

Two probiotic strains of Lactiplantibacillus plantarum protect intestinal cells from oxidative stress and apoptosis by boosting antioxidant defenses.

## Contribution

Discovery of two L. plantarum strains that protect intestinal cells via activation of the Keap1/Nrf2/HO-1 pathway and reduced apoptosis.

## Key findings

- WB3801 and WB3808 reduced oxidative stress and preserved mitochondrial integrity in HT-29 cells.
- These strains activated the Keap1/Nrf2/HO-1 pathway and upregulated antioxidant enzymes like SOD1 and CAT.
- They attenuated apoptosis by reducing the Bax/Bcl-2 ratio and suppressing caspase activation.

## Abstract

Oxidative stress, primarily triggered by elevated levels of reactive oxygen species (ROS) contributes to intestinal epithelial injury and apoptosis, and is closely associated with gastrointestinal disorders. In this study, we evaluated the cytoprotective effects of three Lactiplantibacillus plantarum strains (WB3801, WB3804, and WB3808) isolated from Korean kimchi against H2O2-induced oxidative stress in HT-29 cells. The strains exhibited markedly strong acid and bile tolerance, as well as high adhesion to HT-29 cells, confirming their probiotic potential. These strains exhibited significantly improved cell viability under oxidative stress, reduced intracellular ROS levels, and preserved mitochondrial integrity. These strains enhanced cellular antioxidant defenses by activating the Keap1/Nrf2/HO-1 pathway, upregulating SOD1 and CAT, and demonstrating notable free radical scavenging activity in DPPH and ABTS assays. Flow cytometry and gene expression analyses revealed that WB3801 and WB3808 attenuated apoptosis by reducing the Bax/Bcl-2 ratio and suppressing the activation of caspase-9 and caspase-3. These findings suggest that WB3801 and WB3808 exert potent antioxidant and anti-apoptotic effects through both enzymatic defense and direct radical scavenging, ultimately protecting the intestinal epithelial cells from oxidative damage. The strong cytoprotective activity of these strains supports their potential use as functional probiotics for maintaining intestinal homeostasis and preventing oxidative stress–related intestinal disorders.