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迷迭香酸作为一种保护脑细胞线粒体的有前途的药物。

Carnosic Acid as a Promising Agent in Protecting Mitochondria of Brain Cells.

机构信息

Departamento de Química/ICET, Universidade Federal de Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP 78060-900, Cuiaba, MT, Brazil.

出版信息

Mol Neurobiol. 2018 Aug;55(8):6687-6699. doi: 10.1007/s12035-017-0842-6. Epub 2018 Jan 15.

Abstract

Carnosic acid (CA; CHO), a phenolic diterpene characterized as an ortho-dihydroquinone-type molecule, is a pro-electrophile agent that becomes an electrophile after reacting with free radicals. The electrophile generated from CA interacts with and activates the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, which is a major modulator of redox biology in mammalian cells. CA induces antioxidant and anti-inflammatory effects in several cell types, as observed in both in vitro and in vivo experimental models. In this context, CA has been viewed as a neuroprotective agent by activating signaling pathways associated with cell survival during stressful conditions. Indeed, CA exhibits the ability to promote mitochondrial protection in neural cells. Mitochondria are the main source of both ATP and reactive species in animal cells. Mitochondrial dysfunction plays a central role in the start and development of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, among others. Therefore, the study of strategies aiming to reduce mitochondrial impairment in the case of neurodegeneration is of pharmacological interest. In the present review, it is described and discussed the effects of CA on brain mitochondria in experimental models of neural lesion. Based on the data discussed here, CA is a potential candidate to be listed as a neuroprotective agent by acting on the mitochondria of neural cells.

摘要

迷迭香酸(CA;CHO)是一种酚类二萜,其特征为邻位二氢醌型分子,是一种亲电试剂,在与自由基反应后成为亲电试剂。CA 生成的亲电试剂与核因子红细胞 2 相关因子 2(Nrf2)转录因子相互作用并激活该因子,后者是哺乳动物细胞氧化还原生物学的主要调节剂。CA 在几种细胞类型中诱导抗氧化和抗炎作用,这在体外和体内实验模型中均有观察到。在这种情况下,CA 通过激活与应激条件下细胞存活相关的信号通路被视为神经保护剂。事实上,CA 具有促进神经细胞中线粒体保护的能力。线粒体是动物细胞中 ATP 和活性物质的主要来源。线粒体功能障碍在神经退行性疾病(如阿尔茨海默病、帕金森病和亨廷顿病等)的起始和发展中起着核心作用。因此,研究旨在减少神经退行性病变中线粒体损伤的策略具有药理学意义。在本综述中,描述并讨论了 CA 在神经损伤实验模型中对脑线粒体的影响。基于这里讨论的数据,CA 通过作用于神经细胞的线粒体,是一种有潜力的神经保护剂候选物。

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