Apoptotic Inhibition of Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Induced Dopaminergic Neuronal Cell Death By Ethanolic Extract Bacopa Monnieri

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disease which causes rigidity, resting tremor and postural instability. Baccopa monnieri (BM), a herb traditionally recognized as brain tonic by the Indian system of medicine, Ayurveda. The present study investigates the mechanisms of neuroprotection elicited by ethanolic extract of BM in MPTP mice model system MATERIAL AND METHODS: Male Swiss albino mice weighing 30-40 gram were used in experiment. Experimental mice were given 15mg/kg b.w of MPTP for two weeks and then subsequently treatment of BM 40mg/kg bodyweight orally for one month. Inhibition of apoptotic pathways was studied via behavioral, biochemical, Immunohistochemical and expression analysis. RESULTS: An ethanolic extract of BM was co-treated with the MPTP induced mouse model of PD and was shown to significantly rescue the motor behaviour (Rotarod, Grip Strength and Foot Printing test). Furthermore, on biochemical parameters BM significantly showed marked improvement and the levels of Dopamine, DOPAC and HVA were enhanced significantly. There was a significant reduction in tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra (SN) in the MPTP treated group, which was considerably restored by the use of BM extract. BM also facilitated neuroprotection by creating an antiapoptotic environment indicated by reduced apoptotic (Bax and caspase-3) and increased levels of antiapoptotic (Bcl2) protein expression, respectively. CONCLUSION: Present study suggests that BM treatment provides nigrostriatal dopaminergic neuroprotection against MPTP induced Parkinsonism by the modulation of oxidative stress and apoptotic machinery possibly accounting for the behavioural effects. KEYWORDS: neurodegenerative; antioxidant; Baccopa monnerri; substantia nigra; caspase-3; apoptotic.