Yu Xingzhi, Tao Jie, Xiao Tian, Duan Xiaohua
Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine, Kunming, Yunnan, China.
Front Aging Neurosci. 2024 May 22;16:1414956. doi: 10.3389/fnagi.2024.1414956. eCollection 2024.
is the dried tuber of the orchid Bl. It is considered a food consisting of a source of precious medicinal herbs, whose chemical composition is relatively rich. and its extracted fractions have been shown to have neuroprotective effects. -hydroxybenzaldehyde (-HBA), as one of the main active components of , has anti-inflammatory, antioxidative stress, and cerebral protective effects, which has potential for the treatment of Alzheimer's disease (AD). The aim of this study was to verify the role of -HBA in AD treatment and to investigate its mechanism of action in depth based using the () model.
In this study, we used paralysis, lifespan, behavioral and antistress experiments to investigate the effects of -HBA on AD and aging. Furthermore, we performed reactive oxygen species (ROS) assay, thioflavin S staining, RNA-seq analysis, qPCR validation, PCR Array, and GFP reporter gene worm experiment to determine the anti-AD effects of -HBA, as well as in-depth studies on its mechanisms.
-HBA was able to delay paralysis, improve mobility and resistance to stress, and delay aging in the AD nematode model. Further mechanistic studies showed that ROS and lipofuscin levels, Aβ aggregation, and toxicity were reduced after -HBA treatment, suggesting that -HBA ameliorated Aβ-induced toxicity by enhancing antioxidant and anti-aging activity and inhibiting Aβ aggregation. -HBA had a therapeutic effect on AD by improving stress resistance, as indicated by the down-regulation of NLP-29 and UCR-11 expression and up-regulation of PQN-75 and LYS-3 expression. In addition, the gene microarray showed that -HBA treatment played a positive role in genes related to AD, anti-aging, ribosomal protein pathway, and glucose metabolism, which were collectively involved in the anti-AD mechanism of -HBA. Finally, we also found that -HBA promoted nuclear localization of DAF-16 and increased the expression of SKN-1, SOD-3, and GST-4, which contributed significantly to inhibition of Aβ toxicity and enhancement of antioxidative stress.
Our work suggests that -HBA has some antioxidant and anti-aging activities. It may be a viable candidate for the treatment and prevention of Alzheimer's disease.
[药材名称]是兰科植物[植物名称]的干燥块茎。它被认为是一种由珍贵草药组成的食物，其化学成分相对丰富。并且其提取成分已显示具有神经保护作用。对羟基苯甲醛（p-HBA）作为[药材名称]的主要活性成分之一，具有抗炎、抗氧化应激和脑保护作用，这为治疗阿尔茨海默病（AD）提供了潜力。本研究的目的是验证p-HBA在AD治疗中的作用，并基于秀丽隐杆线虫（Caenorhabditis elegans）模型深入研究其作用机制。
在本研究中，我们使用麻痹、寿命、行为和抗应激实验来研究p-HBA对AD和衰老的影响。此外，我们进行了活性氧（ROS）测定、硫黄素S染色、RNA测序分析、qPCR验证、PCR阵列和绿色荧光蛋白报告基因线虫实验，以确定p-HBA的抗AD作用，并对其机制进行深入研究。
在AD线虫模型中，p-HBA能够延缓麻痹、改善运动能力和抗应激能力，并延缓衰老。进一步的机制研究表明，p-HBA处理后ROS和脂褐素水平、Aβ聚集和毒性降低，这表明p-HBA通过增强抗氧化和抗衰老活性以及抑制Aβ聚集来改善Aβ诱导的毒性。p-HBA通过改善抗应激能力对AD具有治疗作用，这表现为NLP-29和UCR-11表达下调以及PQN-75和LYS-3表达上调。此外，基因芯片显示p-HBA处理在与AD、抗衰老、核糖体蛋白途径和葡萄糖代谢相关的基因中发挥了积极作用，这些基因共同参与了p-HBA的抗AD机制。最后，我们还发现p-HBA促进了DAF-16的核定位，并增加了SKN-1、SOD-3和GST-4的表达，这对抑制Aβ毒性和增强抗氧化应激有显著贡献。
我们的工作表明p-HBA具有一定的抗氧化和抗衰老活性。它可能是治疗和预防阿尔茨海默病的一个可行候选药物。
