Standardized extract of Withania somnifera (Ashwagandha) markedly offsets rotenone-induced locomotor deficits, oxidative impairments and neurotoxicity in Drosophila melanogaster.

Withania somnifera (Ashwagandha,WS) or Indian
ginseng possesses multiple pharmacological properties which
are mainly attributed to the active constituents, withanolides.
Despite its extensive usage as a memory enhancer and a nerve
tonic, few attempts have been made to ascertain its usage in
the management of Parkinson’s disease. In the present study,
we investigated the neuroameliorative effects of WS in a
rotenone (ROT) model of Drosophila melanogaster
(Oregon-K). Initially, we ascertained the ability of WSenriched
diet (0–0.05 %) to protect against ROT induced
lethality and locomotor phenotype in adult male flies.
Further, employing a co-exposure paradigm, we investigated
the propensity of WS to offset ROT-induced oxidative stress,
mitochondrial dysfunctions and neurotoxicity. WS conferred
significant protection against ROT-induced lethality, while the
survivor flies exhibited improved locomotor phenotype.
Biochemical investigations revealed that ROT-induced oxidative
stress was significantly diminished by WS enrichment.
WS caused significant elevation in the levels of reduced GSH/
non-protein thiols. Furthermore, the altered activity levels of
succinate dehydrogenase, MTT, membrane bound enzymes
viz., NADH-cytochrome-c reductase and succinatecytochrome-
c reductase were markedly restored to normalcy.
Interestingly, ROT-induced perturbations in cholinergic function
and depletion in dopamine levels were normalized by
WS. Taken together these data suggests that the
neuromodulatory effect of WS against ROT- induced neurotoxicity
is probably mediated via suppression of oxidative
stress and its potential to attenuate mitochondrial dysfunctions.
Our further studies aim to understand the underlying
neuroprotective mechanisms of WS and withanolides
employing neuronal cell models.