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. Affnity 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.

Key words: nerve regeneration, quercetin, μ-calpain, molecular docking, molecular dynamics simulation; hypoxia, neuroprotection, neural regeneration