Astragaloside IV inhibits the p53/p-Drp1 axis to improve mitochondrial integrity and reduce apoptosis in dorsal root ganglion neurons following oxaliplatin induction

AS-IV ameliorates oxaliplatin-induced damage to DRG neurons. • AS-IV exerts neuroprotective effects by inhibiting the p53/p-Drp1 signaling pathway in OIPN. • AS-IV corrects mitochondrial dysfunction and energy metabolism disorders in OIPN. • AS-IV improves mechanical hyperalgesia and thermal hypersensitivity in OIPN rats. • AS-IV antagonizes OIPN through the p53/p-Drp1/mitochondrial axis. Objective This study targeted to explore the effect of Astragaloside IV (AS-IV) on oxaliplatin (OHP)-induced peripheral neuropathy (OIPN). Methods OHP-induced rat dorsal root ganglion (DRG) neurons were treated with AS-IV and/or p53 inhibitors or agonists. Cell viability, apoptosis, mitochondrial membrane potential, ROS, oxidative stress-related indicators, and mitochondrial complex activity were examined. The interaction between p53 and Drp1 was explored and validated. In vivo , an OIPN rat model was established via intraperitoneal injections of OHP and treated with AS-IV. Behavioral assessments were conducted, and histological examinations were performed on DRG tissues from OIPN rats. Results AS-IV significantly enhanced DRG neuronal viability following OHP induction, inhibited apoptosis, improved mitochondrial function, alleviated oxidative stress, and simultaneously suppressed OHP-induced p53 upregulation and its interaction with Drp1. p53 inhibitors mimicked these protective effects, while agonists blocked these effects. In vivo experiments demonstrated that AS-IV significantly alleviated cold, heat, and mechanical pain sensitivity in OIPN rats, reduced DRG histopathological damage and neuronal apoptosis, improved oxidative stress, and inhibited activation of the p53/p-Drp1 signaling pathway. Conclusion AS-IV protects DRG neurons from OHP-induced injury and alleviates OIPN-related symptoms by inhibiting the p53/p-Drp1 axis.