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

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.