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在实验性诱导的脑型疟疾小鼠模型中评估查耳酮衍生物作为抗寄生虫和神经保护剂的作用。

Evaluation of chalcone derivatives for their role as antiparasitic and neuroprotectant in experimentally induced cerebral malaria mouse model.

作者信息

Sinha Shweta, Medhi Bikash, Radotra B D, Batovska Daniela, Markova Nadezhda, Sehgal Rakesh

机构信息

Department of Medical Parasitology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012 India.

Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

出版信息

3 Biotech. 2023 Jul;13(7):260. doi: 10.1007/s13205-023-03676-y. Epub 2023 Jul 1.

Abstract

UNLABELLED

Cerebral malaria is a severe complication of infection with a complex pathophysiology. The current course of treatment is ineffective in lowering mortality or post-treatment side effects such as neurological and cognitive abnormalities. Chalcones are enormously distributed in spices, fruits, vegetables, tea, and soy-based foodstuffs that are well known for their antimalarial activity, and in recent years they have been widely explored for brain diseases like Alzheimer's disease. Therefore, considering the previous background of chalcones serving as both antimalarial and neuroprotective, the present study aimed to study the effect of these chalcone derivatives on an experimental model of cerebral malaria (CM). CM-induced mice were tested behaviorally (elevated plus maze, rota rod test, and hanging wire test), biochemically (nitric oxide estimation, cytokines (IL-1, IL-6, IL-10, IL-12p70, TNF, IFN-y), histopathologically and immunohistochemically, and finally ultrastructural changes were examined using a transmission electron microscope. All three chalcones treated groups showed a significant ( < 0.001) decrease in percentage parasitemia at the 10th day post-infection. Mild anxiolytic activity of chalcones as compared to standard treatment with quinine has been observed during behavior tests. No pigment deposition was observed in the QNN-T group and other chalcone derivative treated groups. Rosette formation was seen in the derivative 1 treated group. The present derivatives may be pioneered by various research and science groups to design such a scaffold that will be a future antimalarial with therapeutic potential or, because of its immunomodulatory properties, it could be used as an adjunct therapy.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s13205-023-03676-y.

摘要

未标注

脑型疟疾是感染的一种严重并发症,其病理生理过程复杂。目前的治疗方案在降低死亡率或治疗后副作用(如神经和认知异常)方面效果不佳。查耳酮广泛存在于香料、水果、蔬菜、茶和大豆类食品中,这些食品以其抗疟活性而闻名,近年来它们在阿尔茨海默病等脑部疾病方面得到了广泛研究。因此,考虑到查耳酮兼具抗疟和神经保护的既往背景,本研究旨在研究这些查耳酮衍生物对脑型疟疾(CM)实验模型的影响。对CM诱导的小鼠进行行为学测试(高架十字迷宫试验、转棒试验和悬线试验)、生化测试(一氧化氮测定、细胞因子(IL-1、IL-6、IL-10、IL-12p70、TNF、IFN-γ))、组织病理学和免疫组织化学测试,最后使用透射电子显微镜检查超微结构变化。所有三个查耳酮治疗组在感染后第10天的疟原虫血症百分比均显著降低(<0.001)。在行为测试中,与用奎宁进行的标准治疗相比,观察到查耳酮具有轻度抗焦虑活性。在QNN-T组和其他查耳酮衍生物治疗组中未观察到色素沉着。在衍生物1治疗组中观察到玫瑰花结形成。本衍生物可能会被各种研究和科学团队率先用于设计这样一种支架,它将成为未来具有治疗潜力的抗疟药物,或者由于其免疫调节特性,可作为辅助治疗药物。

补充信息

在线版本包含可在10.1007/s13205-023-03676-y获取的补充材料。

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