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

Abstract

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.

Myricetin Isolated From Turbinaria Ornata Ameliorates Rotenone Induced Parkinsonism in Drosophila Melanogaster

“…myricetin alone treated group IV shows nearly similar concentration of dopamine (8.45 µg) like group I control. The results of behavioral study and levels of dopamine are very much supported by earlier different study [27].…”

Neuromodulatory effect of solvent fractions of Africa eggplant (Solanium dadyphyllum) against KCN-induced mitochondria damage, viz. NADH-succinate dehydrogenase, NADH- cytochrome c reductase, and succinate-cytochrome c reductase

“…All the solvent fractions of S. dasyphyllum were able to reverse the inhibitory effect of KCN on ETC enzymes. One of the central point in the mechanism of disease prevention by phytochemicals is through the protection of mitochondria against injury [27][28][29]. Such phytochemicals are found in plants like baicalein, Parkia biglobosa, Antiaris africana and curcumin [30][31][32][33].…”

Current Understanding on the Beneficial Role of Nutrition in Parkinson’s Disease –An Overview

“…The protective efficacy of WS root extracts, against oxidative stress and degeneration of hippocampal cells in vivo under stress conditions have been reported [40]. Recent studies have demonstrated the neuroprotective effect of WS extract in rotenone models in both Drosophila and mice models [41].…”