Molecular Neurobiology ( IF 4.6 ) Pub Date : 2023-08-03 , DOI: 10.1007/s12035-023-03521-6 Kexin Wang 1 , Xinyue Zhang 1 , Miaosi Zhang 1 , Xin Li 1 , Jiao Xie 2 , Suwen Liu 3 , Qun Huang 2 , Jilite Wang 4 , Qingbin Guo 1 , Hao Wang 1
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Traditional Chinese medicines such as hyperoside-rich Acanthopanax senticosus and Crataegus pinnatifida have been confirmed to exhibit anti-oxidative stress properties. Hyperoside, the main ingredient of numerous antioxidant herbs, may have the ability to postpone the onset of neurodegenerative diseases. This study investigates the possible therapeutic mechanism of hyperoside as a natural antioxidant against Alzheimer’s disease (AD) in Caenorhabditis elegans and PC12 cells. Specifically, hyperoside reduced reactive oxygen species (ROS) level and Aβ42-induced neurotoxicity in C. elegans worms. Meanwhile, hyperoside reduced ROS production and increased mitochondrial membrane potentialin Aβ42-induced PC12 cells, which possibly due to the increase of antioxidant enzymes activity and the diminution of malondialdehyde levels. Hoechst 33,342 staining and flow cytometry analysis results suggested that hyperoside reverses cell apoptosis. Network pharmacology predicts potentially relevant hyperoside targets and pathways in AD therapy. As anticipated, hyperoside reversed Aβ42-stimulated downregulation of the PI3K/Akt/Nrf2/HO-1. The PI3K inhibitor LY294002 partially abolished the protective capability of hyperoside. The results of molecular docking further indicated that the PI3K/Akt pathways may be involved in the protection of Aβ42-induced PC12 cells by hyperoside treatment. The study provides theoretical information for research and development of hyperoside as an antioxidant dietary supplement.
Graphical Abstract
中文翻译：
金丝桃苷可预防 Aβ42 诱导的 PC12 细胞和秀丽隐杆线虫神经毒性
富含金丝桃苷的中药刺五加和山楂等已被证实具有抗氧化应激特性。金丝桃苷是许多抗氧化草药的主要成分，可能具有推迟神经退行性疾病发作的能力。本研究探讨了金丝桃苷作为天然抗氧化剂对抗秀丽隐杆线虫和 PC12 细胞中阿尔茨海默病 (AD) 的可能治疗机制。具体而言，金丝桃苷可降低线虫中的活性氧 (ROS) 水平和 Aβ42 诱导的神经毒性。同时，金丝桃苷减少了Aβ42诱导的PC12细胞中ROS的产生并增加了线粒体膜电位，这可能是由于抗氧化酶活性的增加和丙二醛水平的降低所致。 Hoechst 33,342 染色和流式细胞术分析结果表明金丝桃苷可逆转细胞凋亡。网络药理学预测 AD 治疗中潜在相关的金丝桃苷靶点和途径。正如预期的那样，金丝桃苷逆转了 Aβ42 刺激的 PI3K/Akt/Nrf2/HO-1 下调。 PI3K抑制剂LY294002部分消除了金丝桃苷的保护能力。分子对接结果进一步表明PI3K/Akt通路可能参与金丝桃苷处理对Aβ42诱导的PC12细胞的保护作用。该研究为金丝桃苷作为抗氧化膳食补充剂的研发提供了理论信息。
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