State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology, No. 29, 13Th Avenue, Economic and Technological Development Area (TEDA), Tianjin, 300457, People's Republic of China.
Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guizhou, 550025, People's Republic of China.
Mol Neurobiol. 2023 Dec;60(12):7136-7150. doi: 10.1007/s12035-023-03521-6. Epub 2023 Aug 3.
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.
传统中药如富含桃叶珊瑚苷的刺五加和山楂已被证实具有抗氧化应激特性。桃叶珊瑚苷是许多抗氧化草药的主要成分，可能具有延缓神经退行性疾病发病的能力。本研究探讨了桃叶珊瑚苷作为一种天然抗氧化剂治疗阿尔茨海默病（AD）的可能机制，在秀丽隐杆线虫和 PC12 细胞中进行了研究。具体而言，桃叶珊瑚苷可降低秀丽隐杆线虫中活性氧（ROS）水平和 Aβ42 诱导的神经毒性。同时，桃叶珊瑚苷可减少 Aβ42 诱导的 PC12 细胞中 ROS 的产生并增加线粒体膜电位，这可能是由于抗氧化酶活性的增加和丙二醛水平的降低。Hoechst 33,342 染色和流式细胞术分析结果表明，桃叶珊瑚苷可逆转细胞凋亡。网络药理学预测了 AD 治疗中桃叶珊瑚苷相关的潜在靶点和途径。如预期的那样，桃叶珊瑚苷逆转了 Aβ42 刺激的 PI3K/Akt/Nrf2/HO-1 下调。PI3K 抑制剂 LY294002 部分消除了桃叶珊瑚苷的保护作用。分子对接的结果进一步表明，PI3K/Akt 途径可能参与了桃叶珊瑚苷处理对 Aβ42 诱导的 PC12 细胞的保护作用。该研究为将桃叶珊瑚苷作为一种抗氧化膳食补充剂的研究和开发提供了理论信息。
