Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, 999078, China; The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou, 510230, China.
Guangzhou National Laboratory, Guangzhou, 510005, China.
J Ethnopharmacol. 2025 Jan 10;336:118678. doi: 10.1016/j.jep.2024.118678. Epub 2024 Aug 8.
Yupingfeng powder (YPF) is a classic traditional Chinese medicine prescription with a long history of clinical application. However, there is a consensus on the clinical efficacy of YPF in the prevention and treatment of influenza, the underlying pharmacological mechanisms and functional substances have not been thoroughly investigated.
This study aimed to elucidate the functional substances and potential mechanisms of YPF against influenza infections by integrating network analysis, metabolomics, computational system pharmacology, and in vitro experiments.
In this study, the active ingredients, related targets, and potential mechanisms of YPF against influenza were identified through network pharmacology and GEO database mining. Combined with metabolomics to corroborate the results of network pharmacology analysis and construct C-T-P-D-M network. Based on this, the key network motifs (KNM) with significance were predicted by system pharmacology algorithm. Finally, the key components as functional substances in the KNM were validated by the coverage of influenza-causing genes and functional pathways, and in vitro experiments.
A total of 238 active components and 158 potential target genes intersecting with influenza infection differential genes were screened from YPF. KEGG enrichment analysis indicated that metabolism participated in YPF-provided prevention and treatment on influenza, and metabolomic results further corroborated the significance of the metabolic pathways intervened by YPF included pyruvate metabolism, Valine, leucine and isoleucine degradation, etc. The KNM prediction strategy was computed to include wogonin and isoimperaporin, a group of 48 potential functional components. This functional component group maintained a high degree of consistency with the corresponding C-T network in terms of the coverage of influenza pathogenic genes, and the coverage of functional pathways. Meanwhile, the in vitro results showed that wogonin and isoimperaporin had significant inhibitory effects on inflammation induced by influenza infection, confirming the reliability and accuracy of the KNM prediction strategy.
YPF against influenza has multi-target and multi-pathway effects, and the underlying mechanisms may be related to metabolism. The pharmacodynamic effects of core components such as wogonin and isoimperaporin on influenza prevention and treatment were confirmed, which represent promising functional candidates for subsequent influenza prevention and treatment, and provide references for the pharmacological and mechanistic analyses of subsequent formulas.
玉屏风散（YPF）是一种具有悠久临床应用历史的经典中药方剂。然而，对于 YPF 在流感预防和治疗中的临床疗效，目前已经达成共识，但其潜在的药理机制和功能物质尚未得到彻底研究。
本研究旨在通过整合网络分析、代谢组学、计算系统药理学和体外实验，阐明 YPF 防治流感的功能物质和潜在机制。
本研究通过网络药理学和 GEO 数据库挖掘，确定了 YPF 防治流感的活性成分、相关靶点和潜在机制。结合代谢组学结果对网络药理学分析结果进行验证，并构建 C-T-P-D-M 网络。在此基础上，通过系统药理学算法预测关键网络基元（KNM）并进行显著性预测。最后，通过流感致病基因和功能途径的覆盖度以及体外实验，对 KNM 中的关键成分（功能物质）进行验证。
从 YPF 中筛选出与流感感染差异基因相交的 238 个活性成分和 158 个潜在靶点基因。KEGG 富集分析表明，代谢参与了 YPF 对流感的防治作用，代谢组学结果进一步证实了 YPF 干预的代谢途径的重要性，包括丙酮酸代谢、缬氨酸、亮氨酸和异亮氨酸降解等。KNM 预测策略计算出包括汉黄芩素和异欧前胡素在内的一组 48 个潜在功能成分。该功能成分组在覆盖流感致病基因和功能途径方面与相应的 C-T 网络保持高度一致性。同时，体外实验结果表明，汉黄芩素和异欧前胡素对流感感染引起的炎症具有显著的抑制作用，证实了 KNM 预测策略的可靠性和准确性。
YPF 防治流感具有多靶点、多途径的作用，其潜在机制可能与代谢有关。证实了汉黄芩素和异欧前胡素等核心成分对流感防治的药效作用，为后续流感防治提供了有前途的功能候选物，并为后续配方的药理和机制分析提供了参考。
