Neuroprotective Potential of Withania Somnifera in Rotenone Induced Parkinsonism in Mice

• Main Author: C, Kushal Rao Madhaw
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2010
• Subjects: Aging; Amyotrophic lateral sclerosis; Mutation; Neurodegeneration; Neurosciences; Parkinsons disease; Pathology; Pharmaceutical sciences
• ISBN: 9798380006330

Back ground Withania somnifera (WS),traditionally used to improve mental health in Indian ayurvedic system of medicine is known to possess various neuropharmacolgical properties. Environmental toxins like rotenone, a known neurotoxin is demonstrated to increase oxidative stress and mitochondrial dysfunctions.ObjectiveThe present study was planned to assess neuroprotective ability of WS extract against rotenone induced oxidative damage and mitochondrial dysfunctions in prepubertal mice.Methods Sub lethal doses of rotenone (i.p. 0.5, 1.0 mg/kg body wt) daily for 7 days were employed to induce of oxidative stress and mitochondrial dysfunctions in various regions of prepubertal mice. Terminally, oxidative markers (ROS, MDA, HP, NO), antioxidant enzymes (CAT, SOD, GST, GPx), mitochondrial impairments (SDH, MTT, ETC enzymes) and cholinergic function (AChE) were determined. Neuroprotective efficacy of Withania somniferastandardized extract (prophylactic treatment for 2 and 3 weeks and challenged with sub-acute doses of rotenone for 7 days) was determined by redox status, mitochondrial dysfunction and cholinergic function.Results Administration of ROT (i.p. 0.5 and 1mg/kg bw/d for 7days) to prepubertal mice resulted in significant oxidative stress (in vitro), mitochondrial dysfunction and altered cholinergic function in vivoInterpretation and conclusion Collectively our investigation summarizes, Withania somniferahas potential to abrogate significantly rotenone induced oxidative stress and mitochondrial dysfunctions in various regions of prepubertal mice brain. It is hypothesized that the neuroprotective effect of WS extract may be related to its multiple free radical scavenging potency, ability to enhance antioxidant defenses, GSH levels and redox status.