Integrated network pharmacology, transcriptomics and experimental validation to explore mechanisms of Wenyang Jiedu Granule on IAVinduced pneumonia

doi:https://doi.org/10.1016/j.chmed.2026.02.004

Archive > Volume 18 Issue 2 > 2026,18(2):241-261. DOI:https://doi.org/10.1016/j.chmed.2026.02.004 Prev Next

整合网络药理学、转录组学与实验验证探究温阳解毒颗粒干预甲型流感病毒致肺炎的作用机制

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Integrated network pharmacology, transcriptomics and experimental validation to explore mechanisms of Wenyang Jiedu Granule on IAVinduced pneumonia

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摘要:

目的：温阳解毒颗粒是临床常用的有效中药制剂，广泛用于治疗呼吸道感染性疾病。数千例临床观察证实，该药可延缓病情进展、改善临床症状，对新型冠状病毒、流感病毒等呼吸道病毒感染均有干预作用。但温阳解毒颗粒干预甲型流感病毒所致肺炎的物质基础与具体作用机制尚不明确。本研究联合运用网络药理学、转录组学及体内外实验验证，探究温阳解毒颗粒治疗甲型流感病毒肺炎的潜在作用机制。方法：采用 H1N1 甲型流感病毒感染 BALB/c 小鼠构建病毒性肺炎模型，评价温阳解毒颗粒的治疗药效。运用超高效液相色谱 - 四极杆静电场轨道阱串联质谱技术，分析含药血清中的主要入血化学成分；结合肺组织病理形态观察、空斑实验、生化指标检测、伊文思蓝染色及免疫荧光染色等实验，明确其整体药效。联合网络药理学与转录组学筛选温阳解毒颗粒抗甲型流感病毒肺炎的潜在活性成分、作用靶点及相关信号通路；最后采用 TUNEL 荧光凋亡检测、实时荧光定量 PCR、蛋白质免疫印迹实验开展机制验证。结果：经质谱鉴定，小鼠灌胃温阳解毒颗粒后，血清中共鉴定得到25 个原型成分与15 个代谢产物。动物实验证实，温阳解毒颗粒可显著抑制肺部炎症反应、修复肺组织屏障损伤，对甲型流感病毒诱导的小鼠肺炎具有明显保护作用。组学联合分析结果显示，温阳解毒颗粒主要依靠 11 种活性成分协同起效，通过调控 86 个核心靶点、介导 10 条关键信号通路发挥治疗作用。体内实验进一步证实，温阳解毒颗粒可通过调控IL-17 信号通路、TLR7/MyD88/MAPKs/AP-1 信号通路及细胞凋亡进程，改善甲型流感病毒所致肺部炎症损伤。结论：本研究明确了温阳解毒颗粒抗甲型流感病毒肺炎的主要入血活性成分，证实其可通过调控 IL-17 通路、TLR7/MyD88/MAPKs/AP-1 通路及细胞凋亡发挥药效，为该方剂用于流感及其并发症的临床防治提供了科学实验依据与新思路。

Abstract:

Objective: Wenyang Jiedu Granule (WYJD) is an effective traditional Chinese medicine (TCM) preparation that has been generally applied for treating respiratory infectious diseases. Clinical observations involving thousands of cases have demonstrated that WYJD could alleviate disease progression and improve symptoms in treating respiratory viral infections, including SARS-CoV-2 and influenza virus. However, the chemical basis and underlying mechanisms of WYJD against influenza A virus (IAV)-induced pneumonia remain to be elucidated. This study aimed to reveal the underlying mechanisms of WYJD in treating IAV-induced pneumonia by a combined strategy of network pharmacology, transcriptomics and experimental validation. Methods: The pneumonia model was established in BALB/c mice via infection with H1N1 IAV to evaluate the therapeutic effects of WYJD on IAV-induced pneumonia. Firstly, ultra-high performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometer/tandem mass spectrometer (UPLC-Q Exactive Orbitrap-MS/MS) was employed to analyze the main chemical components in WYJDcontaining serum. Subsequently, the effects of WYJD on IAV-induced pneumonia were assessed through pathological observation, plaque forming assay, biochemical analysis, Evans blue staining assay, and immunofluorescence assay. Mechanistically, an integrated approach of network pharmacology and transcriptomics was applied to explore the potential active components, targets and related pathways of WYJD against IAV-induced pneumonia. Fluorescence TUNEL assay, quantitative real-time PCR (qRTPCR) and Western blotting were utilized for experimental validation and mechanistic studies. Results: Using UPLC-Q Exactive Orbitrap-MS/MS, a total of 25 prototypes and 15 metabolites were identified in the serum of mice after WYJD administration. WYJD treatment showed protective effects on IAVinduced pneumonia by inhibiting inflammation and lung barrier damage in the IAV-induced pneumonia mice model. Network pharmacology combined with transcriptomics analysis indicated that WYJD exerted therapeutic effects against IAV-induced pneumonia mainly through the synergistic effects of 11 active components, which regulated ten critical signaling pathways via 86 targets. Further experimental validation demonstrated that WYJD could alleviate IAV-induced pneumonia via the IL-17 signaling pathway, Toll-like receptor 7 (TLR7)/Myeloid differentiation primary response dene 88 (MyD88)/mitogen-activated protein kinases (MAPKs)/activator protein 1 (AP-1) signaling pathway and apoptosis. Conclusion: This study revealed the main active components and mechanisms of WYJD against IAVinduced pneumonia through the IL-17 signaling pathway, TLR7/MyD88/MAPKs/AP-1 signaling pathway and apoptosis, which provides novel insights into the clinical application of WYJD in treating influenza and its complications.

关键词:

细胞凋亡;炎症;甲型流感病毒所致肺炎;肺屏障损伤;网络药理学;转录组学;温阳解毒颗粒

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Project Supported:

This work was supported by grants from the National Natural Science Foundation of China (No. 82374392), Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China (No. HQL2024PZ022).

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整合网络药理学、转录组学与实验验证探究温阳解毒颗粒干预甲型流感病毒致肺炎的作用机制

Original articles

Integrated network pharmacology, transcriptomics and experimental validation to explore mechanisms of Wenyang Jiedu Granule on IAVinduced pneumonia

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