ORIGINAL RESEARCH article
Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1512727
Whole genome sequencing shows modulation of neurodegenerative genes by Withania somnifera in human SK-N-SH cells
Provisionally accepted
Eshita Sharma1,2
Dilip Mehta1,2Nikita Jadhav3Dhananya S4Manju Moorthy4Gopalakrishna Ramaswamy4
Sujit Nair1,2*- 1Phytoveda Pvt. Ltd, Mumbai, India
- 2Viridis BioPharma Pvt. Ltd., Mumbai, Maharashtra, India
- 3University of Toledo, Toledo, Ohio, United States
- 4Theracues Innovations Pvt. Ltd.,, Bengaluru, India
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Background: Aging is driven by several primary and secondary hallmarks that manifest with age, of which neurodegenerative diseases are important manifestations. The ability to decelerate or reverse aging, and promote healthy aging, has garnered great interest in recent times. In traditional medicine, Withania somnifera (WS) or Ashwagandha has been recognized for its adaptogenic and rejuvenative effects. Methods: To investigate WS-modulated global gene expression profiles, we performed whole genome sequencing of WS-treated human neuroblastoma SK-N-SH cells at different doses (50 and 100 μg/mL) and time points (3h and 9h) and validation by quantitative real-time PCR (qRT-PCR) and immunoblotting. Disease enrichment analysis for brain-related disorders was performed by DisGeNET. Results: Using differential gene expression analyses, we identified 19,945 WS-modulated genes. Of these, 2403 and 177 genes were significantly (P≤0.05) upregulated and downregulated respectively by WS treatment. Interestingly, different patterns of gene expression were exhibited in dose-dependent (9 upregulated, 1 downregulated, 100 µg/mL 3h vs 50 µg/mL 3h; 21 upregulated, 86 downregulated, 100 µg/mL 9h vs 50 µg/mL 9h) and temporal kinetics (210 upregulated, 6 downregulated, 50 µg/mL 9h vs 50 µg/mL 3h; 8 upregulated, 49 downregulated, 100 µg/mL 9h vs 100 µg/mL 3h). Further, qRT-PCR experiments validated the RNA-seq results. WS-modulated genes were implicated in Alzheimer's disease, migraine, Parkinson’s disease, bipolar disorder, cognition, stress, anxiety, forgetfulness, sleep disorders and substance abuse amongst others. Conclusion: Taken together, our transcriptomic profiling study revealed for the first time that WS may modulate key genes in neurodegenerative disorders with potential beneficial implications for brain-related disorders and healthy aging.
Keywords: Withania somnifera, Ashwagandha, whole genome sequencing, neurodegenerative 54 disease, Aging, healthy aging 55
Received: 18 Oct 2024; Accepted: 23 May 2025.
Copyright: © 2025 Sharma, Mehta, Jadhav, S, Moorthy, Ramaswamy and Nair. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sujit Nair, Phytoveda Pvt. Ltd, Mumbai, India
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