title: A possible therapeutic potential of quercetin through inhibition of μ-calpain in hypoxia induced neuronal injury: a molecular dynamics simulation study.
abstract: The neuroprotective property of quercetin is well reported against hypoxia and ischemia in past studies. This property of quercetin lies in its antioxidant property with blood-brain barrier permeability and anti-inflammatory capabilities. µ-Calpain, a calcium ion activated intracellular cysteine protease causes serious cellular insult, leading to cell death in various pathological conditions including hypoxia and ischemic stroke. Hence, it may be considered as a potential drug target for the treatment of hypoxia induced neuronal injury. As the inhibitory property of µ-calpain is yet to be explored in details, hence, in the present study, we investigated the interaction of quercetin with µ-calpain through a molecular dynamics simulation study as a tool through clarifying the molecular mechanism of such inhibition and determining the probable sites and modes of quercetin interaction with the µ-calpain catalytic domain. In addition, we also investigated the structure-activity relationship of quercetin with μ-calpain. Affinity binding of quercetin with µ-calpain had a value of -28.73 kJ/mol and a Ki value of 35.87 µM that may be a probable reason to lead to altered functioning of µ-calpain. Hence, quercetin was found to be an inhibitor of µ-calpain which might have a possible therapeutic role in hypoxic injury.
authors.affiliation: School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, India.
authors.forename: Anand Kumar
authors.initials: AK
authors.lastname: Pandey
authors.affiliation: School of Biochemical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, India.
authors.forename: Swet Chand
authors.initials: SC
authors.lastname: Shukla
authors.affiliation: School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, India; Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Pallab
authors.initials: P
authors.lastname: Bhattacharya
authors.affiliation: School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, India.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Patnaik
keywords: hypoxia; molecular docking; molecular dynamics simulation; nerve regeneration; neural regeneration; neuroprotection; quercetin; μ-calpain