Neuroprotective effects of Withania somnifera in the SH-SY5Y Parkinson cell model
Open accessAbstract
Parkinson's disease is the most frequent neurodegenerative motor disorder. The clinical syndrome and pathology involve motor disturbance and the degeneration of dopaminergic neurons in the substantia nigra. Root extracts of Withania. somnifera , commonly called Ashwagandha, contain several major chemical constituents known as withanolides. Studies have shown that W. somnifera extracts exhibit numerous therapeutic effects including inflammation and oxidative stress reduction, memory and cognitive function improvement. This study aimed to evaluate the protective effects of KSM-66, W. somnifera root extract, on 6-hydroxydopamine (6-OHDA)-induced toxicity in the human neuroblastoma SH-SY5Y cell line, as well as the associated oxidative response protein expression and redox regulation activity focused on S-glutathionylation. SH-SY5Y cells were treated with 6-OHDA preceded or followed by treatment with the KSM-66 extract. Using KSM-66 concentrations ranging from 0.25 to 1 mg/ml before and after treatment of the cells with 6-OHDA has resulted in an increased viability of SH-SY5Y cells. Interestingly, the extract significantly increased glutathione peroxidase activity and thioltransferase activity upon pre- or post- 6-OHDA treatment. KSM-66 also modulated oxidative response proteins: peroxiredoxin-I, VGF and vimentin proteins upon 6-OHDA pre/post treatments. In addition, the extract controlled redox regulation via S-glutathionylation. Pre-treatment of SH-SY5Y cells with KSM-66 decreased protein-glutathionylation levels in the cells treated with 6-OHDA. The rescue of mitochondria with 0.5 mg/ml KSM-66 extract showed an increase in ATP levels. These findings suggest that W. somnifera root extract acts as a neuroprotectant, thereby introducing a potential agent for the treatment or prevention of neurodegenerative diseases.
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Withania somnifera is predominantly active against neurological conditions like Alzheimer's disease, Parkinson's disease, and Huntington's disease.
“Moreover, it was found that WS is predominantly active against many neurological conditions like AD, Parkinson's disease, and Huntington's disease [144,145].”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [145]
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Jaiswal, A., Gill, J., Kharwar, R. N., & Singh, B. N. (2026) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2026.108729
- Authors
- Wongtrakul, J., Thongtan, T., Kumrapich, B., Saisawang, C., & Ketterman, A. J.
- Affiliations
- Chiang Mai University (TH)
- Chulalongkorn University (TH)
- Mahidol University (TH)
- Corresponding author
- Wongtrakul, Jeerang
- Ketterman, Albert J.
- Venue
- Heliyon
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 7
- Issue
- 10
- Pages
- e08172
- ISSN
- 2405-8440 (ISSN-L)
- PMC
- PMC8569401
- OpenAlex
- W3205297924
- Cited by
- 52
- References
- 52
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 17 · 2023: 11 · 2022: 2
- FWCI
- 8.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Heliyon (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Greater South Information System
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- Withania somnifera, ashwagandha root extract, Parkinson's disease, neuroprotection, SH-SY5Y cells, withanolides, oxidative stress, S-glutathionylation, glutathione peroxidase, glutaredoxin, peroxiredoxin 1, VGF, vimentin, mitochondrial function, ATP levels, dopaminergic neurons
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