Vishnumurthy Rajendra Herur, Priya M Gnana Ruba, Tiwari Prashant, Solomon Viswas Raja
College of Pharmaceutical Sciences, Dayananda Sagar University, Bengaluru, Karnataka 560111, India.
Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy 502 294, India.
Curr Pharm Des. 2025;31(4):320-329. doi: 10.2174/0113816128298289240723103828.
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.
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.
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.
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.
阿尔茨海默病（AD）是一种令人衰弱的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，具有神经保护、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，本研究旨在评估微囊化塞来昔布（MCXB）的神经保护作用。
使用AutoDock（5.2版）通过分子对接研究筛选CXB，并选择以下蛋白质，如4EY7、2HM1、2Z5X和1PBQ来预测其神经保护作用。对白化大鼠给予20mg/kg/天的东莨菪碱，持续约7天。分别给予100mg/kg/天和200mg/kg/天的纯CXB以及100mg/kg/天和200mg/kg/天的MCXB。此外，为评估氧化应激，使用化学方法评估一氧化氮（NO）、超氧化物歧化酶（SOD）、过氧化氢酶和脂质过氧化（LPO）。使用酶联免疫吸附测定（ELISA）方法评估乙酰胆碱酯酶（AChE）、谷氨酸和多巴胺等神经化学生物标志物。此外，对脑细胞进行组织病理学检查以评估神经元的神经再生和神经退行性变。
CXB（得分-6.3、-6.5、-5.1、-9.1）和多奈哌齐（得分-5.5、-7.6、-7.0和-8.6）分别与乙酰胆碱酯酶（4EY7）、β-分泌酶（2HM1）、单胺氧化酶（2Z5X）和谷氨酸（1PBQ）存在显著的结合相互作用。与东莨菪碱处理的大鼠相比，MCXB处理的大鼠（100mg/kg/天，200mg/kg/天）超氧化物歧化酶水平升高（p<0.001），而一氧化氮、过氧化氢酶和脂质过氧化水平显著降低（p<0.001）。此外，MCXB处理的大鼠在多巴胺和乙酰胆碱酯酶水平上表现出调节作用。然而，谷氨酸水平显著降低（p<0.001）。
除此之外，海马部分的组织病理学检查显示脑细胞有显著改善。因此，结果表明MCXB以剂量依赖的方式对东莨菪碱诱导的AD具有神经保护作用。这种作用可能归因于胆碱能途径的激活。
