Neuroinflammation inhibition and neuroprotective effects of purpurin, a potential anti-AD compound, screened via network proximity and gene enrichment analyses.
Jun Zhao, Pengfei Guo, Jiansong Fang, Chao Wang, Caiqin Yan, Yiming Bai, Zhe Wang, Guanhua Du, Ailin Liu
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引用次数: 0
Abstract
Alzheimer's disease (AD) is a complex neurodegenerative disease without any effective preventive or therapeutic drugs. Natural products with stable structures and pharmacological characteristics are valuable sources for the development of novel drugs for many complex diseases. This study aimed to discover potential natural compounds for the treatment of AD using new technologies and methods and explore the efficacy and mechanism of candidate compounds. AD-related large-scale genetic datasets were collated to construct disease-PPIs and natural products were collected from six databases to construct compound-protein interactions (CPIs). Potential relationships between natural compounds and AD were predicted via network proximity and gene enrichment analyses. Then, five AD-related cell models and d-galactose-induced aging rat model were established to evaluate the neuroprotective effects of candidate compounds in vitro and in vivo. We identified that 267 natural compounds were predicted to have close connections with AD and 19 compounds could exert protective effect in at least one cell model. Notably, purpurin exerted protective effect in three cell models and significantly improved the cognitive learning and memory functions, reduced the oxidative stress injuries and neuroinflammation, and enhanced the synaptic plasticity and neurotrophic effect in the brain of d-galactose-treated rats. In this study, AD-related natural compounds were identified via network proximity and gene enrichment analyses. In vivo and in vitro experiments revealed the therapeutic potential of purpurin for AD treatment, laying the foundation for further in-depth research and providing valuable information for the development of novel anti-AD drugs.
阿尔茨海默病(AD)是一种复杂的神经退行性疾病,目前尚无有效的预防或治疗药物。具有稳定结构和药理特性的天然产物是开发治疗多种复杂疾病的新型药物的宝贵来源。本研究旨在利用新技术和新方法发现治疗AD的潜在天然化合物,并探索候选化合物的疗效和机制。研究人员整理了与AD相关的大规模基因数据集,构建了疾病-蛋白质相互作用(disease-PPIs),并从六个数据库中收集了天然产物,构建了化合物-蛋白质相互作用(CPIs)。通过网络邻近性和基因富集分析预测了天然化合物与 AD 之间的潜在关系。然后,建立了五个与AD相关的细胞模型和d-半乳糖诱导的衰老大鼠模型,以评估候选化合物在体外和体内的神经保护作用。我们发现有 267 种天然化合物被预测与 AD 有密切联系,其中 19 种能在至少一种细胞模型中发挥保护作用。值得注意的是,紫嘌呤在三种细胞模型中发挥了保护作用,并显著改善了认知学习和记忆功能,降低了氧化应激损伤和神经炎症,增强了d-半乳糖处理大鼠大脑的突触可塑性和神经营养效应。本研究通过网络邻近性和基因富集分析发现了与AD相关的天然化合物。体内和体外实验揭示了紫皮素治疗AD的潜力,为进一步深入研究奠定了基础,并为开发新型抗AD药物提供了宝贵信息。
期刊介绍:
Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field.
Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters.
By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.