Aqueous Leaf Extract of Withania somnifera as a Potential Neuroprotective Agent in Sleep-deprived Rats: a Mechanistic Study

Mol Neurobiol. 2017 May;54(4):3050-3061. doi: 10.1007/s12035-016-9883-5. Epub 2016 Apr 1.


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.

Keywords: Ashwagandha; Cell survival; Neuroprotection; Sleep deprivation; Synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Survival / drug effects
  • Female
  • Homeostasis / drug effects
  • Immunohistochemistry
  • Memory / drug effects
  • Models, Biological
  • Motor Activity / drug effects
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity / drug effects
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Plant Leaves / chemistry*
  • Rats, Wistar
  • Sleep Deprivation / drug therapy*
  • Sleep Deprivation / pathology
  • Sleep Deprivation / physiopathology
  • Stress, Physiological / drug effects
  • Withania / chemistry*


  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Plant Extracts