Yang Mengfei, Zhang Xiuying, Liu Qing, Wang Yongxue
Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China.
Department of Pediatrics, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China.
Chin Herb Med. 2024 Jul 29;16(4):638-655. doi: 10.1016/j.chmed.2024.07.007. eCollection 2024 Oct.
Qingfei Tongluo Plaster (QFP), an improved Chinese medicine hospital preparation, is an attractive treatment option due to its well clinical efficacy, convenience, economy, and patient compliance in the treatment of respiratory syncytial virus (RSV) pneumonia. The aim of this study was to investigate the efficacy mechanism of QFP on RSV rats from the perspective of alleviating lung inflammation and further explore the changes of serum metabolites and metabolic pathways in RSV rats under the influence of QFP.
This study used network pharmacological methods and molecular docking combined with molecular biology and metabolomics from multi-dimensional perspectives to screen and verify the therapeutic targets. Open online databases were used to speculate the gene targets of efficient ingredients and diseases. Then, we used the String database to examine the fundamental interaction of common targets of drugs and diseases. An online enrichment analysis was performed to predict the functional pathways. Molecular docking was applied to discover the binding modes between essential ingredients and crucial gene targets. Finally, we demonstrated the anti-inflammatory ability of QFP in the RSV-evoked pneumonia rat model and explained the mechanism in combination with the metabolomics results.
There were 19 critical targets defined as the core targets: tumor necrosis factor (), inducible nitric oxide synthase 2 (), mitogen-activated protein kinase 14 (), g1/S-specific cyclin-D1 (), signal transducer and activator of transcription 1-alpha/beta (), proto-oncogene tyrosine-protein kinase Src (), cellular tumor antigen p53 (), interleukin-6 (), hypoxia-inducible factor 1-alpha (), RAC-alpha serine/threonine-protein kinase (), signal transducer and activator of transcription 3 (), heat shock protein HSP 90-alpha (), tyrosine-protein kinase JAK2 (), cyclin-dependent kinase inhibitor 1 (), mitogen-activated protein kinase 3 (), epidermal growth factor receptor (), myc proto-oncogene protein (), protein c-Fos () and transcription factor p65 (). QFP treated RSV pneumonia mainly through the phosphatidylinositol 3-kinase (PI3K)/RAC AKT pathway, HIF-1 pathway, IL-17 pathway, TNF pathway, and MAPK pathway. Animal experiments proved that QFP could effectively ameliorate RSV-induced pulmonary inflammation. A total of 28 metabolites underwent significant changes in the QFP treatment, and there are four metabolic pathways consistent with the KEGG pathway analyzed by network pharmacology, suggesting that they may be critical processes related to treatment.
These results provide essential perspicacity into the mechanisms of action of QFP as a promising anti-RSV drug.
清肺通络膏（QFP）是一种改良的中医院制剂，因其在治疗呼吸道合胞病毒（RSV）肺炎方面具有良好的临床疗效、便利性、经济性和患者依从性，是一种有吸引力的治疗选择。本研究旨在从减轻肺部炎症的角度探讨QFP对RSV感染大鼠的疗效机制，并进一步探索QFP影响下RSV感染大鼠血清代谢物及代谢途径的变化。
本研究采用网络药理学方法、分子对接，并结合分子生物学和代谢组学从多维角度筛选和验证治疗靶点。利用公开的在线数据库推测有效成分和疾病的基因靶点。然后，使用String数据库检查药物和疾病共同靶点的基本相互作用。进行在线富集分析以预测功能途径。应用分子对接来发现关键成分与关键基因靶点之间 的结合模式。最后，我们在RSV诱发的肺炎大鼠模型中证实了QFP的抗炎能力，并结合代谢组学结果解释其机制。
确定了19个关键靶点为核心靶点：肿瘤坏死因子（）、诱导型一氧化氮合酶2（）、丝裂原活化蛋白激酶14（）、G1/S特异性细胞周期蛋白D1（）、信号转导子和转录激活子1-α/β（）、原癌基因酪氨酸蛋白激酶Src（）、细胞肿瘤抗原p53（）、白细胞介素-6（）、缺氧诱导因子1-α（）、RAC-α丝氨酸/苏氨酸蛋白激酶（）、信号转导子和转录激活子3（）、热休克蛋白HSP 90-α（）、酪氨酸蛋白激酶JAK2（）、细胞周期蛋白依赖性激酶抑制剂1（）、丝裂原活化蛋白激酶3（）、表皮生长因子受体（）、原癌基因c-Myc蛋白（）、原癌基因c-Fos蛋白（）和转录因子p65（）。QFP治疗RSV肺炎主要通过磷脂酰肌醇3激酶（PI3K）/RAC AKT途径、HIF-1途径、IL-17途径、TNF途径和MAPK途径。动物实验证明，QFP可有效改善RSV诱导的肺部炎症。在QFP治疗中共有28种代谢物发生了显著变化，并且有四条代谢途径与网络药理学分析的KEGG途径一致，表明它们可能是与治疗相关的关键过程。
这些结果为QFP作为一种有前景的抗RSV药物的作用机制提供了重要的见解。
