Wu Yonggang, Yue Shijun
School of Marxism, Shaanxi University of Chinese Medicine, Xi'an, China.
School of Pharmacy, International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine of Hebei Province, Hebei University of Chinese Medicine, Shijiazhuang, China.
Medicine (Baltimore). 2024 Dec 20;103(51):e41028. doi: 10.1097/MD.0000000000041028.
Mugua is a Chinese herbal medicine derived from the dried mature fruit of Chaenomeles speciosa (Sweet) Nakai. This study aimed to dissect the active ingredients and mechanism of Mugua. In the present study, the active components of Mugua were collected and screened through databases combined with UPLC-Q/TOF-MS based qualitative analysis and literature mining, and their potential disease targets were predicted. Then, a network relationship diagram of "component-target-disease-efficacy" was constructed. Moreover, the key active components and core targets were analyzed by molecular docking and in vitro anti-inflammatory assays. The traditional efficacy of Mugua mainly corresponded to 4 diseases, namely, rheumatoid arthritis, diarrhea, edema, and emesis. After screening and comparison, it was found that IL-1β, IL-6, TNF, and epidermal growth factor receptor (EGFR) were the shared inflammatory targets of the 4 diseases. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment results showed that these targets were involved mainly in inflammatory responses and inflammation-related pathways, such as rheumatoid arthritis pathway and TNF signaling pathway. Network topology analysis revealed that succinic acid, cinnamic acid, citric acid, caffeic acid, gallic acid, ursolic acid, malic acid, betulinic acid, and oleanolic acid were the key active components, while IL-1β, IL-6, TNF, and EGFR were the shared core targets of these 4 diseases. These results suggested that Mugua could exert traditional efficacy through multi-component and multi-target synergistic mechanisms. Molecular docking results showed that all key active ingredients could autonomously bind to the shared core targets, and the in vitro anti-inflammatory results further confirmed that all the key active components had good anti-inflammatory activities. The present study found that Mugua mainly intervened in the inflammatory response and pathways by acting on key active components and core targets to exert traditional efficacy, providing a theoretical basis for further in-depth research.
木瓜是一种源自蔷薇科植物贴梗海棠（Sweet）Nakai干燥成熟果实的中药材。本研究旨在剖析木瓜的活性成分及作用机制。在本研究中，通过数据库结合基于超高效液相色谱-四极杆/飞行时间质谱的定性分析和文献挖掘，收集并筛选了木瓜的活性成分，并预测了其潜在的疾病靶点。然后，构建了“成分-靶点-疾病-功效”的网络关系图。此外，通过分子对接和体外抗炎试验分析了关键活性成分和核心靶点。木瓜的传统功效主要对应4种疾病，即类风湿性关节炎、腹泻、水肿和呕吐。经过筛选和比较，发现白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子（TNF）和表皮生长因子受体（EGFR）是这4种疾病的共同炎症靶点。基因本体论和京都基因与基因组百科全书通路富集结果表明，这些靶点主要参与炎症反应和炎症相关通路，如类风湿性关节炎通路和TNF信号通路。网络拓扑分析显示，琥珀酸、肉桂酸、柠檬酸、咖啡酸、没食子酸、熊果酸、苹果酸、桦木酸和齐墩果酸是关键活性成分，而IL-1β、IL-6、TNF和EGFR是这4种疾病的共同核心靶点。这些结果表明，木瓜可通过多成分、多靶点协同机制发挥传统功效。分子对接结果表明，所有关键活性成分均可自主结合共同核心靶点，体外抗炎结果进一步证实所有关键活性成分均具有良好的抗炎活性。本研究发现，木瓜主要通过作用于关键活性成分和核心靶点干预炎症反应及通路，从而发挥传统功效，为进一步深入研究提供了理论依据。
