Aqueous Leaf Extract of Withania somnifera as a Potential Neuroprotective Agent in Sleep-deprived Rats: a Mechanistic Study
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Modern lifestyle and sustained stress of professional commitments in the current societal set up often disrupts the normal sleep cycle and duration which is known to lead to cognitive impairments. In the present study, we report whether leaf extract of Withania somnifera (Ashwagandha) has potential neuroprotective role in acute stress of sleep deprivation. Experiments were performed on three groups of adult Wistar rats: group 1 (vehicle treated-undisturbed sleep [VUD]), group 2 (vehicle treated-sleep deprived [VSD]), and group 3 (ASH-WEX treated-sleep deprived [WSD]). Groups 1 and 2 received single oral feeding of vehicle and group 3 received ASH-WEX orally (140 mg/kg or 1 ml/250 g of body weight) for 15 consecutive days. Immediately after this regimen, animals from group 1 were allowed undisturbed sleep (between 6 a.m. and 6 p.m.), whereas rats of groups 2 and 3 were deprived of sleep during this period. We observed that WSD rats showed significant improvement in their performance in behavioral tests as compared to VSD group. At the molecular level, VSD rats showed acute change in the expression of proteins involved in synaptic plasticity, cell survival, and apoptosis in the hippocampus region of brain, which was suppressed by ASH-WEX treatment thus indicating decreased cellular stress and apoptosis in WSD group. This data suggest that Ashwagandha may be a potential agent to suppress the acute effects of sleep loss on learning and memory impairments and may emerge as a novel supplement to control SD-induced cognitive impairments.
KeywordsAshwagandha Neuroprotection Sleep deprivation Synaptic plasticity Cell survival
Shaffi Manchanda and Taranjeet Kaur are thankful to University Grants Commission (UGC) for fellowship grant under UPE (University with Potential for Excellence) and CPEPA (Centre with Potential for Excellence in Particular Area) schemes during the entire course of study. The infrastructure provided by the University Grants Commission (UGC), India, under UPE and CPEPA schemes and the Department of Biotechnology (DBT), India, under DISC facility is highly acknowledged. This study was funded by DST, Government of India (GOI) project grant to Gurcharan Kaur. Muskan Gupta, Vedangana Saini, and Anuradha Sharma are deeply acknowledged for their help and support during the experimental study. The funding source had no role in the study design; in the collection, analysis, and interpretation of data; in writing of report; and in the decision to submit the article for publication.
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Conflict of Interest
The authors declare that they have no conflict of interest.
- 7.Verma SK, Kumar A (2011) Therapeutic uses of Withania somnifera (Ashwagandha) with a note on withanoloids and its pharmacological actions. Asian J Pharm Clin Res 4(1):1–4Google Scholar
- 8.Konar A, Shah N, Singh R, Saxena N, Kaul SC, Wadhwa R, Thakur MK (2011) Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain derived cells. PLoS ONE 6(11):e27265. doi: 10.1371/journal.pone.0027265 CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Khan MA, Subramaneyaan M, Arora VK, Banerjee BD, Ahmed RS (2015) Effect of Withania somnifera (Ashwagandha) root extract on amelioration of oxidative stress and autoantibodies production in collagen-induced arthritic rats. Journal of Complementary and Integrative Medicine 12(2):117–125CrossRefPubMedGoogle Scholar
- 12.Kulkarni SK, Dhir A (2008) Withania somnifera: an Indian ginseng. Progress in Neuro-Psychopharmacology and Biological Psychiatry 32(5):1093–1105.Google Scholar
- 13.Kataria H, Kumar S, Chaudhary H, Kaur G (2015) Withania somnifera suppresses tumor growth of intracranial allograft of glioma cells. Molecular Neurobiology 1–16Google Scholar
- 15.Gao Q, Liu L, Chen Y, Li H, Yang L, Wang Y, Qian Q (2015) Synaptosome-related (SNARE) genes and their interactions contribute to the susceptibility and working memory of attention-deficit/hyperactivity disorder in males. Progress in Neuro-Psychopharmacology & Biological Psychiatry 57:132–139CrossRefGoogle Scholar
- 17.Gautam A, Kaul SC, Thakur MK (2015) Alcoholic extract of Ashwagandha leaves protects against amnesia by regulation of Arc function. Molecular Neurobiology 1–10. doi 10.1007/s12035-015-9117-2Google Scholar
- 23.Lisman J, Raghvachari S (2014) Biochemical principles underlying the stable maintenance of LTP by the CaMKII/NMDAR complex. Brain ResearchGoogle Scholar
- 45.Mester L, Szabo A, Atlasz T et al (2009) Protection against chronic hypoperfusion-induced retinal neurodegeneration by PARP inhibition via activation of PI-3-kinase Akt pathway and suppression of JNK and p38 MAP kinases. Neurotox Res 16:68–76. doi: 10.1007/s12640-009-9049-6 CrossRefPubMedGoogle Scholar