Pandey Anand Kumar, Shukla Swet Chand, Bhattacharya Pallab, Patnaik Ranjana
School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, India.
School of Biochemical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, India.
Neural Regen Res. 2016 Aug;11(8):1247-53. doi: 10.4103/1673-5374.189186.
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.
槲皮素的神经保护特性在过去的研究中已有充分报道，可对抗缺氧和缺血。槲皮素的这一特性源于其抗氧化特性、血脑屏障通透性和抗炎能力。μ-钙蛋白酶是一种钙离子激活的细胞内半胱氨酸蛋白酶，在包括缺氧和缺血性中风在内的各种病理状况下会造成严重的细胞损伤，导致细胞死亡。因此，它可被视为治疗缺氧诱导的神经元损伤的潜在药物靶点。由于μ-钙蛋白酶的抑制特性尚未得到详细研究，因此，在本研究中，我们通过分子动力学模拟研究，以阐明这种抑制的分子机制并确定槲皮素与μ-钙蛋白酶催化结构域相互作用的可能位点和模式为工具，研究了槲皮素与μ-钙蛋白酶的相互作用。此外，我们还研究了槲皮素与μ-钙蛋白酶的构效关系。槲皮素与μ-钙蛋白酶的亲和结合值为-28.73 kJ/mol，Ki值为35.87 μM，这可能是导致μ-钙蛋白酶功能改变的一个可能原因。因此，发现槲皮素是μ-钙蛋白酶的抑制剂，可能在缺氧损伤中具有潜在的治疗作用。
