BACKGROUND: Berberine has therapeutic potential in central nervous system disorders, however, few studies have investigated the effect of berberine on axonal regeneration in PNS injury models. Thus, this study aims to assess the effects of berberine on axonal regeneration in a peroneal nerve transection rat model. METHODS: Sprague-Dawley rats were divided into two groups: group B, berberine (20 mg/kg) intraperitoneal injection after peroneal nerve transection
and group C, normal saline injection as a control. The sciatic nerve functional index (SNFI) was used to assess functional recovery after nerve injury at 2, 4, and 6 weeks post-transection. Electromyography (EMG) was performed to evaluate quantitative neuromuscular function (latency and amplitude) and the regeneration ratio of the injured nerve was evaluated through histological analysis at 6 weeks post-transection. To analyze the effect of various concentrations of berberine on nerve regeneration, Schwann cell viability was analyzed at 0, 0.1, 0.5, 1.0, 5.0 and 10.0 μM of berberine. RESULTS: At 2 and 4 weeks post-transection, SNFI showed no significant difference between groups B and C. However, at 6 weeks post-transection, the SNFI was significantly higher in group B than in group C. On EMG, the latency and amplitude was significantly lower and higher, respectively, in group B than in group C. Histological analysis showed that the regeneration ratio was significantly higher in group B than in group C. Schwann cell viability was highest when 1.0 μM of berberine was administered (136.7±3.5%), and was significantly higher compared to the groups administered with 0.1 μM (114.5±10.6%) and 0.5 μM (118.5±4.8%). CONCLUSION: Berberine injections have a therapeutic effect on nerve regeneration after peripheral nerve transection. In in vitro studies, a minimum dose of 1.0 μM berberine was required to obtain optimal nerve regeneration. Further in vivo studies are needed to analyze the optimal concentration.