Withania somnifera alleviates parkinsonian phenotypes by inhibiting apoptotic pathways in dopaminergic neurons.
Maneb (MB) and paraquat (PQ) are environmental toxins that have been experimentally used to induce selective damage of dopaminergic neurons leading to the development of Parkinson's disease (PD). Although the mechanism of this selective neuronal toxicity in not fully understood, oxidative stress has been linked to the pathogenesis of PD. The present study investigates the mechanisms of neuroprotection elicited by Withania somnifera (Ws), a herb traditionally recognized by the Indian system of medicine, Ayurveda. An ethanolic root extract of Ws was co-treated with the MB-PQ induced mouse model of PD and was shown to significantly rescue canonical indicators of PD including compromised locomotor activity, reduced dopamine in the substantia nigra and various aspects of oxidative damage. In particular, Ws reduced the expression of iNOS, a measure of oxidative stress. Ws also significantly improved the MB + PQ mediated induction of a pro-apoptotic state by reducing Bax and inducing Bcl-2 protein expression, respectively. Finally, Ws reduced expression of the pro-inflammatory marker of astrocyte activation, GFAP. Altogether, the present study suggests that Ws treatment provides nigrostriatal dopaminergic neuroprotection against MB-PQ induced Parkinsonism by the modulation of oxidative stress and apoptotic machinery possibly accounting for the behavioural effects.
Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India, jaiprakash_biotech@yahoo.co.in.
Jay
J
Prakash
Shikha
S
Chouhan
Satyndra Kumar
SK
Yadav
Susan
S
Westfall
Sachchida Nand
SN
Rai
Surya Pratap
SP
Singh
D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010300:Parkinson Disease / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D032341:Withania / Q000737:chemistry*
D017931:DNA Primers; D010936:Plant Extracts; D004298:Dopamine