The effects of betulinic acid chronic administration on the motor, non-motor behaviors, and globus pallidus local field potential power in a rat model of hemiparkinsonism

OBJECTIVE(S): Parkinson’s disease (PD) is a neurodegenerative disorder involving the central nervous system associated with motor and non-motor impairments. Betulinic acid (BA) is a natural substance considered an antioxidative agent. This study aimed to investigate the therapeutic potential of BA on motor dysfunctions and globus pallidus (GP) local EEG power in a 6-hydroxydopamine (6-OHDA)-induced rat model of hemiparkinsonism. MATERIALS AND METHODS: Adult Wistar rats were categorized into different groups, containing; Sham, PD, and treated groups including different doses of BA (0.5, 5, and 10 mg/kg, IP), and L-dopa (20 mg/kg, PO, as positive control). The lesion was induced in the right medial forebrain bundle by injection of 6-OHDA (20 µg/kg). The treatment was begun just after the approved rotational test induced by apomorphine, 14 days after 6-OHDA administration. Motor behaviors such as catalepsy and stride-length and non-motor responses, including GP local EEG, were then assessed. Also, the levels of GSH, catalase, and concentration of dopamine in the brain tissue were measured. RESULTS: Treatment of hemiparkinsonian rats with BA significantly improved catalepsy and stride-length (P<0.001 and P<0.01, respectively) and GP frequency bands’ powers (P<0.001). Moreover, the activities of GSH (P<0.001), catalase (P<0.001), and the concentration of dopamine (P<0.001) in the brain were increased. CONCLUSION: Current results proved the potent ability of BA to scavenge free radicals and to remove oxidative agents in the brain tissue. This natural product could be considered a possible therapeutic compound for motor and non-motor disorders in PD.