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

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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 WS-enriched 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 succinate-cytochrome-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.

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Abbreviations

WS:

Withania somnifera

ROT:

Rotenone

LPO:

Lipid peroxidation

ROS:

Reactive oxygen species

TBARS:

Thiobarbituric acid reactive substances

MDA:

Malondialdehyde

DCF:

2′, 7′-dichlorofluorescein diacetate

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Acknowledgments

We wish to thank the Director, CFTRI for his encouragement in this study. The first author (MJM) thanks the University Grants Commission (UGC), Government of India for the award of a research fellowship under the Rajeev Gandhi National Fellowship (RGNF) scheme.

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Authors and Affiliations

  1. Department of Biochemistry and Nutrition, CSIR- Central Food Technological Research Institute (CFTRI), Mysore, 570020, India

    M. J. Manjunath &  Muralidhara

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  1. M. J. Manjunath
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Correspondence to Muralidhara.

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Manjunath, M.J., Muralidhara Standardized extract of Withania somnifera (Ashwagandha) markedly offsets rotenone-induced locomotor deficits, oxidative impairments and neurotoxicity in Drosophila melanogaster . J Food Sci Technol 52, 1971–1981 (2015). https://doi.org/10.1007/s13197-013-1219-0

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  • DOI: https://doi.org/10.1007/s13197-013-1219-0

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