A possible therapeutic potential of quercetin through inhibition of mu-calpain in hypoxia induced neuronal injury: a molecular dynamics simulation study

作者：Pandey Anand Kumar^*; Shukla Swet Chand; Bhattacharya Pallab; Patnaik Ranjana^*

来源：Neural Regeneration Research, 2016, 11(8): 1247-1253.

DOI：10.4103/1673-5374.189186

• nerve regeneration
• quercetin
• mu-calpain
• molecular docking
• molecular dynamics simulation
• hypoxia
• neuroprotection
• neural regeneration

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. mu-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 mu-Calpain is yet to be explored in details, hence, in the present study, we investigated the interaction of quercetin with mu-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 mu-Calpain catalytic domain. In addition, we also investigated the structure-activity relationship of quercetin with mu-Calpain. Affinity binding of quercetin with mu-Calpain had a value of -28.73 kJ/mol and a Ki value of 35.87 mu M that may be a probable reason to lead to altered functioning of mu-Calpain. Hence, quercetin was found to be an inhibitor of mu-Calpain which might have a possible therapeutic role in hypoxic injury.

• 出版日期2016-8