Lactiplantibacillus plantarum ZJ316 alleviates the oxidative stress and cellular apoptosis via modulating Nrf2/HO-1 signaling pathway

Oxidative stress plays a key role in the development of gastrointestinal diseases. Disruption of cellular redox balance results in the accumulation of reactive oxygen species, culminating in inflammation and cell apoptosis (blue dashed line). Here, our study highlights the efficacy of supplementing Lactiplantibacillus plantarum ZJ316 or its fermentation supernatant in mitigating cellular oxidative stress, reducing inflammation levels, and decreasing cell apoptosis through the activation of the Nrf2/HO-1 pathway (brown solid line). • Enhanced cell viability under H 2 O 2 -induced oxidative stress by L. plantarum ZJ316 and ZJ316 FS. • Oral probiotics also alleviate oxidative damage induced by D-galactose in mice. • L. plantarum ZJ316 and ZJ316 FS alleviate H 2 O 2 -induced inflammation and apoptosis. • Hindrance of the protective effect by pretreatment with the Nrf2 inhibitor ML385. Oxidative stress is vital in gastrointestinal diseases, but how lactic acid bacteria protect human gastric adenocarcinoma cells (AGS) is unclear. Here, we aimed to investigate Lactiplantibacillus plantarum ZJ316 ( L. plantarum ZJ316) for its potential to alleviate oxidative stress in AGS cells and elucidate mechanisms involved. Treatment with L. plantarum ZJ316 and fermentation supernatant (ZJ316 FS) bolstered cell viability under hydrogen peroxide (H 2 O 2 )-induced oxidative stress, boosting antioxidant enzymes like superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) while reducing reactive oxygen species (ROS) and malondialdehyde (MDA). Oral probiotics also alleviated oxidative damage from D-galactose in mice. Additionally, L. plantarum ZJ316 and ZJ316 FS alleviated H 2 O 2 -induced inflammation and apoptosis by modulating the expression of inflammatory and apoptotic factors. However, the protective effect was hindered when pretreated with the Nrf2 inhibitor ML385. These findings suggest that L. plantarum ZJ316 and fermentation supernatant alleviate oxidative damage by activating the Nrf2/HO-1 pathway, showing promise in development of antioxidant functional foods.