目的:阿尔茨海默病(AD)是一种慢性进行性神经退行性疾病。塞来昔布(CXB)具有有效的抗氧化剂和神经保护,抗炎,和免疫调节特性。然而,CXB的低生物利用度限制了其治疗效用。因此,这项研究旨在评估微囊化的塞来昔布MCXB)的神经保护作用。
方法:使用AutoDock(5.2版)通过分子对接研究筛选CXB,和下列蛋白质,如4EY7,2HM1,2Z5X,选择1PBQ预测其神经保护作用。向白化病大鼠施用东莨菪碱20mg/kg/天,持续约7天。纯CXB100毫克/千克/天和200毫克/千克/天,和MCXB100mg/kg/天和200mg/kg/天,分别。Further,为了评估氧化应激,一氧化氮(NO),超氧化物歧化酶(SOD),过氧化氢酶,和脂质过氧化(LPO)使用化学方法进行评估。像AChE这样的神经化学生物标志物,谷氨酸,使用ELISA方法评估多巴胺和多巴胺。Further,进行脑细胞的组织病理学以评估神经元的神经再生和神经变性。
结果:CXB(评分-6.3,-6.5,-5.1,-9.1)和多奈哌齐(评分-5.5,-7.6,-7.0和-8.6)与AchE(4EY7)存在显着的结合相互作用,β-分泌酶(2HM1,单胺氧化酶(2Z5X),和谷氨酸(1PBQ),分别。MCXB治疗的大鼠(100mg/kg/天,200mg/kg/天)显示SOD水平增加(p<0.001),而NO,过氧化氢酶,与东pol碱治疗的大鼠相比,LPO水平显着降低(p<0.001)。Further,MCXB处理的大鼠对多巴胺和AchE的水平显示出调节作用。然而,谷氨酸水平显著降低(p<0.001)。
结论:除此之外,海马部分的组织病理学检查显示脑细胞显着改善。所以,结果表明,MCXB,以剂量依赖的方式,显示了对东莨菪碱诱导的AD的神经保护作用。这种作用可能归因于胆碱能途径的激活。
OBJECTIVE: Alzheimer\'s Disease (AD) is an enervating and chronic progressive neurodegenerative disorder. Celecoxib (CXB) possesses efficacious antioxidants and has neuroprotective, anti- inflammatory, and immunomodulatory properties. However, the poor bioavailability of CXB limits its therapeutic utility. Thus, this study aimed to evaluate the microencapsulated celecoxib MCXB) for neuroprotection.
METHODS: CXB was screened by molecular docking study using AutoDock (version 5.2), and the following proteins, such as 4EY7, 2HM1, 2Z5X, and 1PBQ were selected for predicting its neuroprotective effect. Scopolamine 20 mg/kg/day for approximately 7 days was administered to albino rats. Pure CXB 100 mg/kg/- day and 200 mg/kg/day, and MCXB 100 mg/kg/day and 200 mg/kg/day were administered, respectively. Further, to assess the oxidative stress, the nitric oxide (NO), superoxide dismutase (SOD), catalase, and lipid peroxidation (LPO) were evaluated using chemical methods. The neurochemical biomarkers like AChE, glutamate, and dopamine were evaluated using the ELISA method. Further, the histopathology of brain cells was carried out to assess the neuro-regeneration and neurodegeneration of the neurons.
RESULTS: There was a significant binding interaction of CXB (score -6.3, -6.5, -5.1, -9.1) and donepezil (score- 5.5, -7.6, -7.0, and -8.6) with AchE (4EY7), β-secretase (2HM1, monoamine oxidase (2Z5X), and glutamate (1PBQ), respectively. MCXB-treated rats (100 mg/kg/day, 200 mg/kg/day) showed increased SOD levels (p < 0.001), whereas NO, catalase, and LPO levels were significantly (p < 0.001) decreased as compared to scopolamine-treated rats. Further, MCXB-treated rats showed a modulatory effect in the level of dopamine and AchE. However, the glutamate level was significantly (p < 0.001) decreased.
CONCLUSIONS: In addition to that, histopathological examination of the hippocampus part showed remarkable improvement in brain cells. So, the findings of the results revealed that MCXB, in a dose-dependent manner, showed a neuroprotective effect against scopolamine-induced AD. This effect may be attributed to the activation of cholinergic pathways.