2. Academic Validation
  3. M1 muscarinic receptor is a key target of neuroprotection, neuroregeneration and memory recovery by i-Extract from Withania somnifera

M1 muscarinic receptor is a key target of neuroprotection, neuroregeneration and memory recovery by i-Extract from Withania somnifera

  • Sci Rep. 2019 Sep 30;9(1):13990. doi: 10.1038/s41598-019-48238-6.
Arpita Konar 1 2,  Richa Gupta 3 4,  Rajendra K Shukla 3 5,  Bryan Maloney 6,  Vinay K Khanna 3,  Renu Wadhwa 7,  Debomoy K Lahiri 8 9,  Mahendra K Thakur 10
Affiliations

Affiliations

  • 1 Biochemistry and Molecular Biology Laboratory, Brain Research Centre, Department of Zoology, Banaras Hindu University, Varanasi, 221005, India.
  • 2 CSIR-Institute of Genomics & Integrative Biology, New Delhi, 110025, India.
  • 3 Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Lucknow, 226001, Uttar Pradesh, India.
  • 4 Devision of ECD, Indian Council of Medical Research, New Delhi, 110029, India.
  • 5 Department of Biochemistry, Autonomous State Medical College, Bahraich, Utter Pradesh, 271801, India.
  • 6 Departments of Psychiatry, Stark Neuroscience Research Institute, Indiana University School of Medicine, 320 West 15th Street, Indianapolis, IN-46202, USA.
  • 7 DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Biomedical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki, 305 8562, Japan. [email protected].
  • 8 Departments of Psychiatry, Stark Neuroscience Research Institute, Indiana University School of Medicine, 320 West 15th Street, Indianapolis, IN-46202, USA. [email protected].
  • 9 Departments of Medical and Molecular Genetics, Indiana Alzheimer Disesae Center, Indiana University School of Medicine, Indianapolis, IN-46202, USA. [email protected].
  • 10 Biochemistry and Molecular Biology Laboratory, Brain Research Centre, Department of Zoology, Banaras Hindu University, Varanasi, 221005, India. [email protected].
PMID: 31570736 DOI: 10.1038/s41598-019-48238-6
Abstract

Memory loss is one of the most tragic symptoms of Alzheimer's disease. Our laboratory has recently demonstrated that 'i-Extract' of Ashwagandha (Withania somnifera) restores memory loss in scopolamine (SC)-induced mice. The prime target of i-Extract is obscure. We hypothesize that i-Extract may primarily target muscarinic subtype acetylcholine receptors that regulate memory processes. The present study elucidates key target(s) of i-Extract via cellular, biochemical, and molecular techniques in a relevant amnesia mouse model and primary hippocampal neuronal cultures. Wild type Swiss albino mice were fed i-Extract, and hippocampal cells from naïve mice were treated with i-Extract, followed by muscarinic antagonist (dicyclomine) and agonist (pilocarpine) treatments. We measured dendritic formation and growth by immunocytochemistry, Kallikrein 8 (KLK8) mRNA by reverse transcription polymerase chain reaction (RT-PCR), and levels of KLK8 and microtubule-associated protein 2, c isoform (MAP2c) proteins by western blotting. We performed muscarinic receptor radioligand binding. i-Extract stimulated an increase in dendrite growth markers, KLK8 and MAP2. Scopolamine-mediated reduction was significantly reversed by i-Extract in mouse cerebral cortex and hippocampus. Our study identified muscarinic receptor as a key target of i-Extract, providing mechanistic evidence for its clinical application in neurodegenerative cognitive disorders.

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