Possible Neuroprotective Effect of Withania somnifera Root Extract Against 3-Nitropropionic Acid-Induced Behavioral, Biochemical, and Mitochondrial Dysfunction in an Animal Model of Huntington's Disease
Abstract
Huntington's disease (HD) is a neurodegenerative disorder that results from the destruction of neurons in the basal ganglia, and oxidative stress has been implicated in its pathogenesis. 3-Nitropropionic acid (3-NP), a potent neurotoxin, has been reported to induce oxidative/nitrosative stress and causes neurobehavioral and biochemical changes that mimic HD in humans. It also inhibits complex II of the mitochondrial electron transport chain, thereby causing cellular energy deficit. In the present work, we evaluated the effects of a well-known antioxidant on behavioral, biochemical, and mitochondrial dysfunction induced by 3-NP. The study was designed to investigate the effects of Withania somnifera root extract against 3-NP-induced gait abnormalities, oxidative stress, and mitochondrial dysfunction in striatum and cortex of rat brain. Intraperitoneal administration of 3-NP (10 mg/kg for 14 days) caused a loss in body weight and a decline in motor function (locomotor activity and impaired rotarod activity). Chronic treatment with W. somnifera root extracts (100 and 200 mg/kg) for a period of 2 weeks dose-dependently improved 3-NP-induced behavioral, biochemical, and enzymatic changes (P < .05). Biochemical analysis revealed that systemic 3-NP administration significantly increased lipid peroxidation and nitrite and lactate dehydrogenase enzyme levels, depleted antioxidant enzyme (superoxide dismutase and catalase) levels, and blocked ATP synthesis by inhibiting the mitochondrial complex activity in the different regions (striatum and cortex) of the brain. Chronic administration of W. somnifera root extract (100 and 200 mg/kg) dose-dependently restored biochemical alterations induced by chronic 3-NP treatment (P < .05). These findings suggest that neuroprotective actions of W. somnifera are mediated via its antioxidant activity. However, further studies are required to elucidate the molecular mechanisms involved in order to support the clinical use of the plant extract as a therapeutic agent for the treatment of HD.
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Neuroprotective activities of Withania somnifera are well documented by many studies.
“Neuroprotective activities of WS have been well documented by many studies.”
From Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects (2021) · cites this paper as [168]
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- Authors
- Kumar, P., & Kumar, A.
- Affiliations
- Panjab University (IN)
- Venue
- Journal of Medicinal Food
- Publisher
- SAGE Publications
- Published
- 2009-06
- Volume
- 12
- Issue
- 3
- Pages
- 591-600
- ISSN
- 1096-620X (ISSN-L)
- 1557-7600
- OpenAlex
- W2039237464
- Cited by
- 120
- References
- 53
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 9 · 2023: 15 · 2022: 8 · 2021: 9 · 2020: 10 · 2019: 3 · 2018: 3 · 2017: 12 · 2016: 8 · 2015: 5 · 2014: 7 · 2013: 9 · 2012: 4
- FWCI
- 9.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Medicinal Food (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Indian National Science Academy
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- Huntington's disease, Withania somnifera, ashwagandha root extract, 3-nitropropionic acid, neuroprotection, oxidative stress, nitrosative stress, mitochondrial dysfunction, complex II inhibition, lipid peroxidation, superoxide dismutase, catalase, ATP production, striatum, cortex, motor impairment, antioxidant activity
- MeSH terms
- Adenosine Triphosphate, Animals, Antioxidants, Behavior, Animal, Brain, Catalase, Disease Models, Animal, Huntington Disease, L-Lactate Dehydrogenase, Male, Phytotherapy, Mitochondria, Motor Activity, Neurotoxins, Nitro Compounds, Oxidoreductases, Plant Extracts, Propionates, Superoxide Dismutase, Lipid Peroxidation, Rats, Wistar, Plant Roots, Neuroprotective Agents, Withania, Rats
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