Neuroprotective Potentials of Berberine in Rotenone-induced Parkinson's Disease-like Motor Symptoms in Rats

Abstract Rotenone (RTN) induces neurotoxic and motor impairments in rats that parallel pathophysiological features of Parkinson's disease (PD), such as striatal oxidative and nitrosative stress, mitochondrial dysfunction, and alterations in neural cytoarchitecture, making RTN a useful model for studying PD. Berberine (BBR), an isoquinoline alkaloid known for its antioxidative, anti-inflammatory, and neuroprotective properties, was tested for its protective effects against RTN-induced dysfunctions in this study. Rats were administered RTN subcutaneously at 0.5 mg/kg for 21 days, leading to weight loss and significant motor deficits as assessed by various tests including open-field, bar catalepsy, beam-crossing, rotarod, and grip strength measurements. BBR was given orally at doses of 30 or 100 mg/kg, 60 minutes prior to RTN, for the same duration and was effective in preventing many RTN-induced motor impairments. Additionally, BBR treatment decreased RTN-induced nitric oxide (NO) and lipid peroxidation (LPO) levels, increase anti-oxidation power, enhanced the activity of mitochondrial enzymes such as succinate dehydrogenase (SDH), ATPase, and the electron transport chain (ETC), and reduced neuroinflammation and apoptosis markers in the striatum. However, the introduction of trigonelline (TGN), an inhibitor of the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway, significantly reduced the protective effects of BBR, suggesting that BBR's neuroprotective actions are mediated through the Nrf2 pathway. These findings highlight BBR's potential to mitigate motor impairments similar to those seen in PD, suggesting its relevance in potentially delaying or managing PD symptoms. Further studies are necessary to translate these preclinical findings into clinical applications, deepening our understanding of BBR's therapeutic potential in PD.