Aurantii Fructus (AF) and Aurantii Fructus Immaturus (AFI) have been used for thousands of years as traditional Chinese medicine (TCM) with sedative effects. Modern studies have shown that Citrus plants also have protective effects on the nervous system. However, the effective substances and mechanisms of action in Citrus TCMs still remain unclear. In order to explore the pharmacodynamic profiles of identified substances and the action mechanism of these herbs, a comprehensive approach combining ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS) analysis and network pharmacology was employed. Firstly, UNIFI 2.1.1 software was used to identify the chemical characteristics of AF and AFI. Secondly, the SwissTargetPrediction database was used to predict the targets of chemical components in AF and AFI. Targets for neuroprotection were also collected from GeneCards: The Human Gene Database (GeneCards-Human Genes|Gene Database|Gene Search). The networks between targets and compounds or diseases were then constructed using Cytoscape 3.9.1. Finally, the Annotation, Visualization and Integrated Discovery Database (DAVID) (DAVID Functional Annotation Bioinformatics Microarray Analysis) was used for GO and pathway enrichment analysis. The results showed that 50 of 188 compounds in AF and AFI may have neuroprotective biological activities. These activities are associated with the regulatory effects of related components on 146 important signaling pathways, derived from the KEGG (KEGG: Kyoto Encyclopedia of Genes and Genomes), such as neurodegeneration (hsa05022), the Alzheimer’s disease pathway (hsa05010), the NF-kappa B signaling pathway (hsa04064), the hypoxia-inducible factor (HIF)-1 signaling pathway (hsa04066), apoptosis (hsa04210), the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance signaling pathway (hsa01521), and others, by targeting 108 proteins, including xanthine dehydrogenase (XDH), glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B), and glucose-6-phosphate dehydrogenase (G6PD), among others. These targets are thought to be related to inflammation, neural function and cell growth.

中文翻译：

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集成UPLC/Q-TOF-MS/MS分析和网络药理学揭示枳壳和枳壳的神经保护机制和潜在药理成分


枳壳（AF）和枳壳（AFI）作为具有镇静作用的中药（TCM）已有数千年的历史。现代研究表明，柑橘类植物对神经系统也有保护作用。然而，柑橘中药的有效物质和作用机制仍不清楚。为了探索已鉴定物质的药效学特征和这些草药的作用机制，采用超高效液相色谱与四极杆飞行时间质谱（UPLC/Q-TOF-MS/MS）分析相结合的综合方法并采用网络药理学。首先利用UNIFI 2.1.1软件对AF和AFI的化学特性进行鉴定。其次，利用SwissTargetPrediction数据库对AF和AFI中化学成分的目标进行预测。神经保护靶标也从 GeneCards：人类基因数据库（GeneCards-人类基因|基因数据库|基因搜索）中收集。然后使用 Cytoscape 3.9.1 构建靶标与化合物或疾病之间的网络。最后，使用注释、可视化和集成发现数据库（DAVID）（DAVID功能注释生物信息学微阵列分析）进行GO和通路富集分析。结果表明，AF和AFI中的188种化合物中有50种可能具有神经保护生物活性。 这些活性与相关成分对146条重要信号通路的调节作用有关，这些信号通路源自KEGG（KEGG：京都基因和基因组百科全书），例如神经退行性变（hsa05022）、阿尔茨海默病通路（hsa05010）、NF- kappa B信号通路（hsa04064）、缺氧诱导因子（HIF）-1信号通路（hsa04066）、细胞凋亡（hsa04210）、表皮生长因子受体（EGFR）酪氨酸激酶抑制剂耐药信号通路（hsa01521）等，通过靶向 108 种蛋白质，包括黄嘌呤脱氢酶 (XDH)、谷氨酸离子型受体 NMDA 型亚基 2B (GRIN2B) 和葡萄糖-6-磷酸脱氢酶 (G6PD) 等。这些目标被认为与炎症、神经功能和细胞生长有关。