Institute of Biotechnology, University of Caxias do Sul, Caxias do Sul, RS, 95070 560, Brazil.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Mol Biol Rep. 2019 Dec;46(6):6013-6025. doi: 10.1007/s11033-019-05037-6. Epub 2019 Aug 26.
Brain disorders (BD) including neuropsychiatric and neurodegenerative diseases, are often associated with impairments in mitochondrial function and oxidative damage that can lead to neuronal injury. The mitochondrial complex I enzyme is one of the main sites of ROS generation and is implicated in many BD pathophysiologies. Despite advances in therapeutics for BD management, conventional pharmacotherapy still cannot efficiently control neuronal redox imbalance and mitochondrial dysfunction. Araucaria angustifolia is one of the main pine species in South America and presents a notable therapeutic history in folk medicine. A. angustifolia extract (AAE), obtained from the natural waste named bracts, is rich in flavonoids; molecules able to regulate cell redox metabolism. We examined the effects of AAE on rotenone-induced mitochondrial complex I dysfunction in human dopaminergic SH-SY5Y cells. AAE restored complex I assembly and activity mainly through overexpression of NDUFS7 protein and NDUFV2 gene levels. These findings were accompanied by a reduction in the generation of neuronal reactive oxygen species and lipid peroxidation. Our data demonstrates, for the first time, that AAE exerts in vitro neuroprotective effects, thus making it an interesting source for future drug development in BD-associated mitochondrial dysfunctions.
脑疾病（BD）包括神经精神和神经退行性疾病，通常与线粒体功能障碍和氧化损伤有关，这些损伤可导致神经元损伤。线粒体复合物 I 酶是 ROS 产生的主要部位之一，与许多 BD 病理生理学有关。尽管 BD 管理的治疗方法取得了进展，但传统的药物治疗仍然不能有效地控制神经元氧化还原失衡和线粒体功能障碍。南洋杉是南美洲主要的松树物种之一，在民间医学中具有显著的治疗历史。南洋杉提取物（AAE）来自天然废物称为苞鳞，富含类黄酮；能够调节细胞氧化还原代谢的分子。我们研究了 AAE 对鱼藤酮诱导的人多巴胺能 SH-SY5Y 细胞中线粒体复合物 I 功能障碍的影响。AAE 主要通过上调 NDUFS7 蛋白和 NDUFV2 基因水平来恢复复合物 I 的组装和活性。这些发现伴随着神经元活性氧生成和脂质过氧化的减少。我们的数据首次表明，AAE 发挥体外神经保护作用，因此成为与 BD 相关的线粒体功能障碍的未来药物开发的有趣来源。
