OBJECTIVE: To study the capability of bioactive compounds to ameliorate the neuronal destruction in animal model of Parkinson disease. MATERIALS AND METHODS:Rotenone was used to produce the Parkinsonism in mammalian model of rats and the bioactive compounds, chrysin, polydatin and CGA were used to ameliorate the neuronal destruction and the resulting effets of Parkinson in this study. A total of hundred male Sprague Dawley albino rats of weight 200 to 250 gm were divided randomly into five groups with twenty animals in each: control, rotenone+chrysin, rotenone+polydatin and rotenone+chlorogenic acid (CGA) group. Rotenone was dissolved in DMSO and migloyl 812 N at ratio of 2:98 respectively and was administered intraperitoneally at a dose of 3 mg/kg, daily for four week to produce the rat model of Parkinson disease. Mortality and weight changes were assessed, various behavioral tests were performed throughout the experiment to assess the neuro behavioral changes. At the end of experiment, animals were sacrificed, brains were fixed by perfusion method and light microscopic sections were prepared using H & E and cresyl violet method. Immunohistochemical sections were also prepared using anti tyrosine hydroxylase antibody, anti α synuclein antibody, anti ubiquitin antibody, to localize the damaged neurons and amelioration done by bioactive compounds. Anti GFAP antibody was used to localize the Astrocytes immunohistochemically. Dopaminergic neurons, α synuclein and ubiquitin aggregations and astrocytes were analysed for anychanges in their morphology and count in substantia nigra and striatum in Parkinsonism and the ameliorating effects of the bioactive compounds used in this study on them. RESULTS:Rotenone-induced Parkinsonism in animals showed a significant loss of body weight and increase in mortality.Parkinson animals showed deteriorating motor behaviour over the period of experiment. Parkinson animals showed a decrease in dopaminergic neurons in nigrostriatal region. TH immunohistochemistry (IHC) showed decreased immunoreactivity and number of TH positive dopaminergic neurons.Ubiquitin and α-synuclein IHC showed accumulation of α-synuclein & ubiquitin within the neuronal cytoplasm. Astrogliosis with increase in number and amoeboid morphology was also seen. Bioactive compounds not only significantly restored the rotenone-induced weight loss but also the behavioural changes. These compounds also showed protective effects in terms of less degeneration of nigrostriatal dopaminergic neurons and diminished immunoreactivity to anti ubiquitin and anti α-synuclein antibodies. These compounds also decreased the activation and number of astrocytes. CONCLUSION:This study concludes that bioactive compounds confer protection in rat model of Parkinson disease. They ameliorated the degeneration of the dopaminergic neurons, accumulation of α-synuclein and ubiquitin in the cytoplasm of neurons and activation & morphological alteration of astrocytes.