Withania somnifera Alleviates Parkinsonian Phenotypes by Inhibiting Apoptotic Pathways in Dopaminergic Neurons

Abstract

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.

Withania somnifera shows ability to counter Parkinson's Disease: An Update

“…Interestingly, it has been suggested in a study that over expression of Bcl-2 helps to attenuate MPTP-induced neuronal cell death [45]. Prakash J et al2014., [6] showed that Bcl-2 expression was significantly down regulated while Bax expression was significantly elevated in a MB-PQ model of PD. Furthermore, it was observed that Ws treatment increased the level of anti-apoptotic (Bcl-2) proteins and decreased the level of the pro-apoptotic (Bax) proteins in the MB-PQ model of PD.…”

“…Thus, through their work they deduced the medicinal benefit of the Indian traditional herb Ws which enhances catecholamines and antioxidants and prevents lipid peroxidation in the corpus striatum of PD mice. Prakash J et al2014., [6] studied the effect of Ws on dopamine and its metabolites in the SN region of PD mice. Reduction of dopamine and its metabolites was found in PD mice brain as compared to controls.…”

“…Solanaceae) is popularly known as "Indian Ginseng" or "Indian Winter cherry" [1,2]. It is an indigenous medicinal plant exhibiting a vital role in the treatment of various diseases such as stress [3], anxiety [4], arthritis [5] and other disorders related to the central nervous system (CNS) such as Parkinson's [6,7] and Alzheimer's disease [8]. In Ayurveda, the Indian system of medicine, use of herbal plant extracts for treating PD has been well documented by [9] in clinical model.…”

“…The biological activity of Ws extract showed antioxidant and free radical scavenging potential [13]. Additionally, Ws is a potent neuronal tonic and has been expected to be used in the treatment of many neurological deficits including epilepsy [14], poor memory [15], depression [4] and PD [6] in animal model. to possess anti-aging [27], anti-oxidant [6] and anti-cancerous properties [28].…”

“…Additionally, Ws is a potent neuronal tonic and has been expected to be used in the treatment of many neurological deficits including epilepsy [14], poor memory [15], depression [4] and PD [6] in animal model. to possess anti-aging [27], anti-oxidant [6] and anti-cancerous properties [28]. Andallu B and Radhika B.2000., [2] demonstrated through clinical observation that roots of Ws are a potential source of hypoglycemic, diuretic and hypocholesterolemic agents.…”