Modulation of GPCR receptors common to gut inflammatory diseases and neuronal disorders, Alzheimer's and Parkinson's diseases as druggable targets through Withania somnifera bioactives: an in silico study

J Biomol Struct Dyn. 2023 Jul;41(10):4485-4503. doi: 10.1080/07391102.2022.2068072. Epub 2022 May 1.


Microorganisms in human gastrointestinal tract have profound influence on the transformation of food into metabolites which can impact human health. Along with playing crucial roles in regulating and modulating various metabolic reactions and life processes, dysbiosis of gut microbiota also affects the permeability of gut and blood-brain barrier. This increases the chance of age-related neurological disorders' like Alzheimer's and Parkinson's diseases. Withania somnifera (W. somnifera) has been proclaimed as a virtuous plant for the treatment of neurodegenerative diseases and many other problems. We have studied the bioactive components of W. somnifera for combined treatment of gut-dysbiosis led bowel diseases (Inflammatory Bowel Disease, Irritable Bowel Syndrome) and the most common neurodegenerative diseases through common potential targets. This approach can solve along with curing the neurodegenerative diseases, the factors causing these diseases would also be obstructed from entering the brain, consonantly curing Inflammatory Bowel Disease and Irritable Bowel Syndrome. Our work on GPCR receptors common to gut inflammatory diseases and neuronal disorders through Network Pharmacology, Molecular docking and Dynamic Simulation approach has shown that modulation of these receptors with bioactive compounds present in W. somnifera can result in effective control of these diseases. We have found five proteins (HTR1A, HTR1B, HTR2A, HTR2B & HTR7) and five best lead compounds (Withanolide A, B, E, Q & Anahygrine) against these targets after molecular docking analysis. Our simulation studies have finally shown that amongst these five HTR1A and HTR7 proteins are the best targets with the leads Withanolide E and Withanolide A against them, respectively.Communicated by Ramaswamy H. Sarma.

Keywords: Alzheimer’s disease; GPCR receptors; Gut-microbiome; Network Pharmacology; Parkinson’s disease; Withania somnifera; inflammatory bowel disease; irritable bowel syndrome.

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Dysbiosis
  • Humans
  • Inflammatory Bowel Diseases*
  • Irritable Bowel Syndrome*
  • Molecular Docking Simulation
  • Neurodegenerative Diseases* / drug therapy
  • Parkinson Disease* / drug therapy
  • Withania*
  • Withanolides* / pharmacology


  • Withanolides