Alam Mohammad Zubair, Bagabir Hala Abubaker, Zaher Mohammad Alameen Faisal, Alqurashi Thamer M A, Alghamdi Badrah S, Kazi Mohsin, Ashraf Ghulam Md, Alshahrany Gadah Ali, Alzahrani Noor Ahmed, Bakhalgi Rafal Mohammed, Al-Thepyani Mona, AboTaleb Hanin Abdulbaset, Aldhahri Rahaf Saeed, El-Aziz Gamal Said Abd, Al-Abbasi Fahad A, Eibani Loay Khaled, Alzahrani Faisal Jaman, Khan Mohd Sajjad Ahmad
Neuroscience and Geroscience Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
Mol Neurobiol. 2025 Jan;62(1):604-625. doi: 10.1007/s12035-024-04310-5. Epub 2024 Jun 18.
Multiple sclerosis (MS) is a neurodegenerative disease characterized by the demyelination of nerves, axonal damage, and neuroinflammation. Cognition impairment, pain, and loss of mobility are some of the usual complications of MS. It has been postulated that the overproduction of proinflammatory cytokines and reactive oxygen species (ROS) are the main factors that contribute to MS pathology. Among various animal models, the cuprizone model is the most widely used model for investigating MS-related pathology. We assessed the effects of cuprizone along with the protective effects of some black seed oil-based nanoformulations of curcumin with and without piperine, in mice hippocampus in terms of the changes in antioxidant enzymes, transcription factors, and cytokines during demyelination and remyelination processes. The results of behavioral studies point toward impairment in working memory following the feeding of cuprizone for 5 weeks. However, in treatment groups, mice seemed to prevent the toxic effects of cuprizone. Nanoformulations used in this study were found to be highly effective in lowering the amount of ROS as indicated by the levels of antioxidant enzymes like catalase, superoxide dismutase, glutathione, and glutathione peroxidase. Moreover, nanoformulations CCF and CCPF were observed resisting the toxic effects of cuprizone. We observed greater expression of NFκB-p65 in the CPZ group than in the control group. CCF nanoformulation had a better inhibitory effect on NFκB-p65 than other formulations. Histological examination of the hippocampus was also conducted. Nanoformulations used here were found effective in reversing MS-related pathophysiology and hence have the potential to be applied as adjuvant therapy for MS treatment.
多发性硬化症（MS）是一种神经退行性疾病，其特征为神经脱髓鞘、轴突损伤和神经炎症。认知障碍、疼痛和行动能力丧失是MS常见的一些并发症。据推测，促炎细胞因子和活性氧（ROS）的过度产生是导致MS病理的主要因素。在各种动物模型中，铜螯合剂模型是研究MS相关病理最广泛使用的模型。我们评估了铜螯合剂以及一些含或不含胡椒碱的基于黑种草油的姜黄素纳米制剂在小鼠海马体中对脱髓鞘和髓鞘再生过程中抗氧化酶、转录因子和细胞因子变化的影响及保护作用。行为学研究结果表明，喂食铜螯合剂5周后工作记忆受损。然而，在治疗组中，小鼠似乎能预防铜螯合剂的毒性作用。本研究中使用的纳米制剂在降低ROS含量方面非常有效，过氧化氢酶、超氧化物歧化酶、谷胱甘肽和谷胱甘肽过氧化物酶等抗氧化酶水平表明了这一点。此外，观察到纳米制剂CCF和CCPF能抵抗铜螯合剂的毒性作用。我们观察到CPZ组中NFκB-p65的表达高于对照组。CCF纳米制剂对NFκB-p65的抑制作用比其他制剂更好。还对海马体进行了组织学检查。这里使用的纳米制剂被发现可有效逆转MS相关的病理生理过程，因此有潜力作为MS治疗的辅助疗法应用。
