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探索多功能水杨酸色胺衍生物对帕金森病的治疗作用。

Exploring the Therapeutic Effects of Multifunctional -Salicylic Acid Tryptamine Derivative against Parkinson's Disease.

作者信息

Li Xuelin, Wang Shuzhi, Duan Shan, Long Lin, Zhuo Linsheng, Peng Yan, Xiong Yongxia, Li Shuang, Peng Xue, Yan Yiguo, Wang Zhen, Jiang Weifan

机构信息

School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.

The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.

出版信息

ACS Omega. 2023 Jul 28;8(31):28910-28923. doi: 10.1021/acsomega.3c04277. eCollection 2023 Aug 8.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Neuroinflammation and oxidative stress play an important role in the whole course of PD, which have been the focus of PD drug development. In our previous research, a series of -salicylic acid tryptamine derivatives were synthesized, and the biological evaluation showed that the compound 02003 has good anti-neuroinflammatory activity and displayed great therapeutic potency for neurodegenerative disease models. In this work, the neuroprotective efficiency of 02003 against PD and has been explored. It was found that 02003 could protect human neuron cells SH-SY5Y from MPP-induced neuronal damage by inhibiting ROS generation, mitochondrial dysfunction, and cellular apoptosis. Moreover, 02003 could improve cognition, memory, learning, and athletic ability in a rotenone-induced PD rat model. In general, our study has demonstrated that 02003 has good activity against PD in and experiments, which can potentially be developed into a therapeutic candidate for PD.

摘要

帕金森病(PD)是全球第二常见的神经退行性疾病。神经炎症和氧化应激在帕金森病的整个病程中起着重要作用,一直是帕金森病药物研发的重点。在我们之前的研究中,合成了一系列水杨酸色胺衍生物,生物学评价表明化合物02003具有良好的抗神经炎症活性,对神经退行性疾病模型显示出巨大的治疗潜力。在这项工作中,探索了02003对帕金森病的神经保护效率。发现02003可通过抑制活性氧生成、线粒体功能障碍和细胞凋亡来保护人神经细胞SH-SY5Y免受MPP诱导的神经元损伤。此外,02003可改善鱼藤酮诱导的帕金森病大鼠模型的认知、记忆、学习和运动能力。总体而言,我们的研究表明02003在体外和体内实验中对帕金森病具有良好的活性,有望开发成为帕金森病的治疗候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c394/10413456/e0a72224584c/ao3c04277_0002.jpg

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