| 摘要: |
| 目的：采用网络药理学及分子对接技术分析胃糜舒颗粒入血成分治疗慢性萎缩性胃炎（chronic atrophic gastritis，CAG）的药效物质基础及作用机制。方法：采用超高效液相色谱-四级杆-飞行时间串联质谱联用仪（ultra performance liquid chromatographyquadrupole-time of flight-mass spectrometry，UPLC-Q-TOF-MS）技术鉴定胃糜舒颗粒及其给药大鼠入血成分，通过网络药理学分析其治疗CAG的潜在机制，构建可视化网络图，并利用分子对接技术进行验证。结果：实验鉴定了胃糜舒颗粒43种入血成分，其中乌桑巴拉碱、柚皮苷、川陈皮素、3,4’,5,6,7,8-六甲氧基黄酮、3,5,7,8,3’,4’-六甲氧基黄酮、1-咖啡酰奎宁酸、肉豆蔻烯酸、藜芦酸、十五烷酸、异丁酸等为治疗CAG的核心成分，主要作用靶点为肿瘤蛋白53（tumor protein 53，TP53）、蛋白激酶B（protein kinase B，PKB/AKT）、信号转导及转录活化因子（signal transducer and activator of transcription，STAT）、表皮生长因子受体（epidermal growth factor receptor，EGFR）等。基因本体（gene ontology，GO）功能富集显示主要生物过程与平滑肌细胞增殖调节、细胞氧化应激反应、对细菌分子的反应、腺体发育、细胞凋亡调控等相关；京都基因与基因组数据库（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集表明胃糜舒颗粒治疗CAG的机制与表皮生长因子受体途径（epidermal growth factor receptor pathway，EGFR pathway）、Janus激酶-信号转导和转录激活因子信号通路（janus kinase-signal transducer and activator of transcription pathway，JAK-STAT pathway）、丝裂原激活的蛋白激酶途经（mitogen-activated protein kinase pathway，MAPK pathway）、磷脂酰肌醇-3-激酶/蛋白激酶B信号通路（phosphoinositide 3-kinase/protein Kinase B signaling pathway，PI3K/AKT pathway）、肿瘤坏死因子/TOLL样受体4-核因子κB信号通路（tumor necrosis factor/toll-like receptor 4-nuclear factor kappa-B signaling pathway，TNF/TLR4-NFκB signaling pathway）、肿瘤蛋白53通路（tumor protein 53 pathway，TP53 pathway）、转化生长因子-β信号通路（transforming growth factor-β signaling pathway，TGF-β signaling pathway）、缺氧诱导因子-1信号通路（hypoxia-inducible factor-1 signaling pathway,HIF-1 signaling pathway）等有关。分子对接验证了核心入血成分与核心作用靶点的强结合能力。结论：研究鉴定了胃糜舒颗粒治疗CAG的药效物质基础，系统揭示了其通过多成分、多靶点、多通路治疗CAG，为深入研究其药效物质及作用机制奠定了基础。 |
| 关键词: 慢性萎缩性胃炎 胃糜舒颗粒 入血成分 UPLC-Q-TOF-MS 网络药理学 分子对接 |
| DOI： |
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| Mechanism of action of the blood-absorbed components of Weimishu granules in treatment of chronic atrophic gastritis: A study based on network pharmacology |
| SU Xiaoling,WANG Shuangxi,YANG Donghua,LUO Hongying,XU Zhiwei,LI Junru,QI Yongfu |
| (Institute of Traditional Chinese Medicine, Qinghai Provincial Hospital of Traditional Chinese Medicine, Xining 810099, Qinghai, China) |
| Abstract: |
| Objective: Investigate the pharmacodynamic material basis and mechanism of action of Weimishu granules in the treatment of chronic atrophic gastritis （CAG） based on network pharmacology and molecular docking. Methods: Ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry （UPLC-Q-TOF-MS） was used to identify the active components of Weimishu granules and the blood-absorbed components of Weimishu granules in rats. Network pharmacology was used to analyze the potential mechanism of the blood-absorbed components in the treatment of CAG, and a visual network was constructed. Molecular docking was used for validation. Results: A total of 43 blood-absorbed components of Weimishu granules were identified, among which Usambarane, naringin, nobiletin, 3-Methoxytangeretin, Gossypetinhexamethylether, 1-caffeoylquinic acid, myristoleic acid, veratric acid, pentadecanoic acid, and isobutyric acid were identified as the core components for the treatment of CAG. The main action targets included tumor protein 53, protein kinase B, signal transducer and activator of transcription, and epidermal growth factor receptor. The gene ontology functional enrichment analysis showed that the main biological processes were associated with the regulation of smooth muscle cell proliferation, cellular oxidative stress response, response to molecule of bacteria, gland development, and regulation of cell apoptosis, and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the mechanism of Weimishu granules in the treatment of CAG was associated with the epidermal growth factor receptor pathway, the Janus kinase-signal transducer and activator of transcription pathway, the mitogen-activated protein kinase pathway, the phosphoinositide 3-kinase/protein kinase B signaling pathway, the tumor necrosis factor/Toll-like receptor 4-nuclear factor-kappa B signaling pathway, the tumor protein 53 pathway, the transforming growth factor-β signaling pathway, and the hypoxia-inducible factor-1 signaling pathway. Molecular docking confirmed the strong binding ability between the core blood-absorbed components and the core action targets. Conclusion: This study identifies the pharmacodynamic material basis of Weimishu granules in the treatment of CAG and systematically reveals that Weimishu granules exert a therapeutic effect on CAG through multiple components, targets, and pathways, which lays a foundation for further research on the pharmacodynamic substances and mechanism of action of Weimishu granules. |
| Key words: chronic atrophic gastritis Weimishu granules ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry network pharmacology molecular docking |
