Department of Medical Biochemistry, Mahatma Gandhi Memorial Medical College, A.B. Road, Indore, 452001, M.P., India.
Center for Nutrition and Food Sciences, Queensland Alliance for Agriculture and Food Innovation, Health and Food Sciences Precinct, University of Queensland, Block 10, 39 Kessels Road, Coopers Plains, Acherfield Brisbane, QLD, 4108, Australia.
Inflammation. 2017 Apr;40(2):623-635. doi: 10.1007/s10753-017-0509-5.
Genistein, an isoflavonoid phytoestrogen, has been known for its potential pharmacological properties especially for neuroprotection and treating diabetes. The present study aims to determine the neuroprotective efficacy of genistein against global cerebral ischemia-reperfusion-induced neuronal injury in streptozotocin-induced diabetic mice and explore the underlying mechanisms. Streptozotocin-induced diabetic mice were subjected to transient cerebral ischemia by occluding both common carotid arteries for 30 min followed by 24 h reperfusion to induce neuronal injury. Effect of genistein (2.5, 5.0, and 10.0 mg/kg, i.p., o.d.) treatment on ischemia-reperfusion-induced neuronal injury in diabetic mice was evaluated in terms of cerebral infarct size, oxidative damage, mitochondrial activity in terms of neuronal apoptosis and cellular viability, dipeptidyl peptidase-4 activity and active glucagon-like peptide-1 concentration, and neurological functions measured as short-term memory and motor performance. Genistein administration following transient cerebral ischemia significantly (p ˂ 0.0001) counteracted cognitive impairment and re-established (p ˂ 0.001) motor performance in diabetic mice. Ischemia-reperfusion increased the infarct size, genistein administration prevented the increase in cerebral infarct size (p ˂ 0.0001) and significantly suppressed (p ˂ 0.001) the increase in cerebral oxidative stress in transient cerebral ischemia-reperfusion subjected diabetic mice. Genistein treatment significantly (p ˂ 0.001) reduced neuronal apoptosis and increased cellular viability (p ˂ 0.0001), almost completely suppressed (p ˂ 0.0001) the circulating dipeptidyl peptidase-4 activity, and enhanced (p ˂ 0.0001) glucagon-like peptide-1 concentration in diabetic mice with cerebral ischemia-reperfusion. This study suggests that genistein has potent neuroprotective activity against global cerebral ischemia-reperfusion-induced neuronal injury and consequent neurological deficits in streptozotocin-induced diabetic mice.
染料木黄酮，一种异黄酮植物雌激素，以其潜在的药理特性而闻名，特别是在神经保护和治疗糖尿病方面。本研究旨在确定染料木黄酮对链脲佐菌素诱导的糖尿病小鼠全脑缺血再灌注诱导的神经元损伤的神经保护作用，并探讨其潜在机制。通过阻断颈总动脉 30 分钟，然后再灌注 24 小时，使链脲佐菌素诱导的糖尿病小鼠发生短暂性脑缺血，以诱导神经元损伤。用染料木黄酮（2.5、5.0 和 10.0mg/kg，腹腔注射，每天一次）处理，评估其对糖尿病小鼠缺血再灌注诱导的神经元损伤的影响，评估指标包括脑梗死面积、氧化损伤、神经元凋亡和细胞活力、二肽基肽酶-4 活性和活性胰高血糖素样肽-1 浓度以及神经功能（短期记忆和运动表现）。短暂性脑缺血后给予染料木黄酮治疗，可显著（p<0.0001）改善糖尿病小鼠的认知障碍，并恢复（p<0.001）其运动表现。缺血再灌注增加梗死面积，染料木黄酮给药可防止脑梗死面积增加（p<0.0001），并显著抑制（p<0.001）糖尿病小鼠短暂性脑缺血再灌注后大脑氧化应激的增加。染料木黄酮治疗可显著（p<0.001）减少神经元凋亡，增加细胞活力（p<0.0001），几乎完全抑制（p<0.0001）循环中二肽基肽酶-4 的活性，并增强（p<0.0001）糖尿病小鼠缺血再灌注后的胰高血糖素样肽-1 浓度。本研究表明，染料木黄酮对链脲佐菌素诱导的糖尿病小鼠全脑缺血再灌注诱导的神经元损伤及随后的神经功能缺损具有强大的神经保护作用。
