MECHANISTIC EVALUATION OF URSOLIC ACID AGAINST ROTENONE INDUCED PARKINSON'S DISEASE- EMPHASIZING THE ROLE OF MITOCHONDRIAL BIOGENESIS.
Клучни зборови
Апстракт
Parkinson's disease (PD) is an age associated, progressive, second most common neurodegenerative disease, caused due to degeneration of dopaminergic neurons in the substantia nigra (SN). Various studies imply mitochondrial dysfunction, oxidative stress, altered degradation of misfolded proteins in PD pathogenesis. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, is reported to possess a number of biological activities viz. anti-oxidant, anti-inflammatory. The focus of our study was to assess the neuroprotective potential of UA against the rotenone induced pathophysiological alterations. In this study rats were subjected to stereotaxic bilateral injection of rotenone (12 µg/µl) in SN. Further, they were treated per-orally with UA (5 and 10 mg/kg) for 30 days. During the study, neurobehavioural studies comprising Rota-rod, open field and Barnes maze test (BMT) were conducted. At the end of 30 days, the antioxidant (Reduced glutathione, superoxide dismutase, catalase and lipid peroxidation), inflammatory (TNF-α) parameters, immunohistochemistry for TH positive neurons, Glial Fibrillary Acidic Protein (GFAP) and mitochondrial complex I and mitochondrial biogenesis (MB) were assessed. The results showed a significant amelioration in the motor deficits by UA which can be attributed to the protection of TH positive neurons degeneration. A significant improvement in the cognitive function due to UA was observed in BMT. Biochemically, the oxidative stress and inflammation triggered by rotenone was significantly diminished by UA. UA also significantly obviated the complex I inhibition and promoted MB. The preliminary results thus firmly advocate the neuroprotective potential of UA to prevent rotenone induced neurotoxicity in rats.