Lycium barbarum polysaccharide LBP3 alleviates 5-Fluorouracil-induced intestinal injury via a mechanism associated with activating Nrf2 and improving mitochondrial function.

Abstract

BACKGROUND: Chemotherapy-induced intestinal injury caused by 5-Fluorouracil (5-FU) severely impairs intestinal barrier integrity through oxidative stress and mitochondrial dysfunction. Currently, effective preventive strategies are lacking. This study investigated the protective effects and mechanisms of LBP3, a bioactive fragment of Lycium barbarum polysaccharides, against chemotherapy-induced intestinal injury. METHODS: 5-FU-induced chemotherapy-induced intestinal injury mouse model and IEC-6 cell model were used to evaluate weight loss, colon pathology, intestinal barrier function, oxidative stress, and mitochondrial dysfunction. The role of the Nrf2 pathway was studied using the inhibitor ML385. RESULTS: LBP3 significantly alleviated body weight loss, colon tissue damage, and inflammatory cell infiltration, and restored the expression of tight junction proteins (Occludin, ZO-1) and barrier integrity. LBP3 reduced reactive oxygen species (ROS) levels, restored superoxide dismutase (SOD) and glutathione (GSH) activity, and decreased malondialdehyde (MDA) accumulation, mitigating oxidative stress. Furthermore, LBP3 improved mitochondrial function by restoring membrane potential and morphology. CONCLUSION: LBP3 alleviates chemotherapy-induced intestinal injury by enhancing antioxidant defenses and mitochondrial protection, has been strongly associated with the activation of Nrf2 pathway. This study highlights LBP3's potential as a therapeutic agent for chemotherapy-induced intestinal injury.