摘要
目的 利用网络药理学及分子对接技术探索穿心莲治疗慢性阻塞性肺疾病的作用机制。方法 从TCMSP中筛出穿心莲活性成分和作用靶点；运用OMIM、Gene Cards等数据库收集COPD疾病靶点。通过Uniprot数据库查询靶点对应的基因，采用ClusterProfiler R软件、String数据库构建PPI网络、GO与KEGG富集分析，使用Cytoscape软件构建中药-化合物-靶点网络图、靶点-富集通路网络图以筛选出核心化合物、靶点以及通路，最后利用Autodock Vina软件对核心靶点和化合物进行分子对接。结果 穿心莲治疗COPD的活性成分23个、靶点67个，核心靶点包括TP53、AKT1、TNF、IL6等；GO功能富集以生物过程为主，包括脂多糖反应、细菌起源分子、金属离子反应等；KEGG通路分析得到148条信号通路，剔除无关通路后，核心富集通路以炎症免疫相关通路为主，包括PI3K−Akt信号通路、AGE−RAGE信号通路、IL−17信号通路、p53信号通路等；分子对接显示穿心莲化合物与IL-6、TNF具有较好的结合活性。结论 穿心莲可能通过汉黄芩素、穿心莲素、槲皮素四甲基醚等多种活性成分，调控AKT1、IL6、TNF、TP53等核心靶点，介导PI3K−Akt、AGE−RAGE、IL−17等炎症免疫相关信号通路，发挥抗炎、抑制氧化应激等作用，从而实现对COPD的治疗效果，其作用机制体现了中医药多成分、多靶点、多通路的特点。本研究首次通过网络药理学与分子对接预测了穿心莲治疗COPD的多靶点协同机制，为后续实验验证与药物开发提供了理论依据。
关键词： 穿心莲；慢性阻塞性肺疾病；网络药理学；分子对接
Abstract
Objective To explore the mechanism of action of Andrographis paniculata Pill (CP) in treating chronic obstructive pulmonary disease (COPD) using network pharmacology and molecular docking techniques. Methods Active components and target sites of Andrographis paniculata were screened from the Traditional Chinese Medicine Systematic Pharmacology Database (TCMSP). COPD disease targets were collected from databases such as OMIM and Gene Cards. Corresponding genes were queried through the Uniprot database. Protein-protein interaction (PPI) networks were constructed using ClusterProfiler R software and String database, followed by GO and KEGG enrichment analyses. Cytoscape software was employed to construct herbal medicine-compound-target networks and target-enriched pathway networks to screen core compounds, targets, and pathways. Finally, molecular docking of core targets and compounds was performed using Autodock Vina software. Results The active components of Andrographis paniculata pills (Chuanxinlian Wan) in the treatment of COPD include 23 active ingredients and 67 targets, with core targets including TP53, AKT1, TNF, IL6, etc. GO functional enrichment primarily focuses on biological processes, such as lipopolysaccharide response, bacterial origin molecules, and metal ion response. KEGG pathway analysis identified 148 signaling pathways. After excluding irrelevant pathways, the core enriched pathways are predominantly inflammation and immunity-related, including the PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, IL-17 signaling pathway, and p53 signaling pathway. Molecular docking revealed that Andrographis compounds exhibit favorable binding activity with IL-6 and TNF. Conclusion Andrographis paniculata pills may exert therapeutic effects on COPD through multiple active components, such as baicalin, Andrographenin, and quercetin tetramethyl ether, by regulating core targets like AKT1, IL6, TNF, and TP53, thereby mediating inflammation and immunity-related signaling pathways such as PI3K-Akt, AGE-RAGE, and IL-17, and exerting anti-inflammatory and oxidative stress-inhibiting effects. This mechanism reflects the characteristics of traditional Chinese medicine, which involves multiple components, targets, and pathways.
Key words： Andrographis paniculata pill; Chronic Obstructive Pulmonary Disease (COPD); Network pharmacology; Molecular docking
参考文献 References
[1] Lin H Q, Wang C X, Yu H, et al. Protective effect of total Saponins from American ginseng against cigarette smoke-induced COPD in mice based on integrated metabolomics and network pharmacology[J]. Biomedicine & Pharma-cotherapy, 2022, 149:112823.
[2] Dong S, Liu Z J, Chen H M, et al. A synergistic mechanism of Liquiritin and Licochalcone B from Glycyrrhiza uralen-sis against COPD[J]. Phytomedicine, 2024, 132:155664.
[3] Xu L T, Wang T, Han Q T, et al. Integrated network pharmacology and pharmacological investigations to explore the potential mechanism of Ding-Chuan-Tang against chronic obstructive pulmonary disease[J]. Journal of Ethnopharmacology, 2024, 327:117983.
[4] 陆曦,许玲,马明华,等.基于网络药理学与分子对接探讨金芪清疏颗粒治疗慢性阻塞性肺疾病稳定期的作用机制 [J]. 河南中医,2026,46 (1):93-100.
[5] 苏苗,洪涛,李娟,等.慢性阻塞性肺疾病血管重塑的发病机制及中药提取物、活性成分及复方干预的研究进展 [J]. 时珍国医国药,2025.
[6] 常兰,赵怀娥,王维.慢性阻塞性肺疾病中西医病因病机及治疗研究进展 [J]. 医药前沿,2025,15 (34):25-28.
[7] 李亚,黄浩轩,赵贵香,等.中医药靶向调控炎症相关信号通路防治慢性阻塞性肺疾病急性加重的研究进展 [J]. 中国中药杂志,2025.
[8] Liao W, Lim A Y H, Tan W S D, et al. Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease[J]. British Journal of Pharmacology, 2020, 177: 3662-3673.
[9] 谢健,邓淑妍,李学莹,等.穿心莲内酯对慢阻肺疾病急性加重期患者的影响 [J]. 广州医药,2022,53 (1):1-6.
[10] 刘佳莉,丁甘玲,汪嘉琦,等.穿心莲内酯对香烟烟雾诱导小鼠肺损伤拮抗作用 [J]. 中国公共卫生,2022,38 (5): 585-588.
[11] 张珍,马丽,毛庆菊.中药注射剂型治疗慢性阻塞性肺疾病急性加重期的研究进展 [J]. 中国中医急症,2024,33 (10):1876-1880.
[12] 牛明,张斯琴,张博,等.《网络药理学评价方法指南》解读 [J]. 中草药,2021,52 (14):4119-4129.
[13] 解静,高杉,李琳,等.网络药理学在中药领域中的研究进展与应用策略 [J]. 中草药,2019,50 (10):2257-2265.
[14] Paggi J M, Pandit A, Dror R O. The Art and Science of Molecular Docking[J]. Annual Review of Biochemistry, 2024, 93:389-410.
[15] Tao X, Huang Y, Wang C, et al. Recent Developments in Molecular Docking Technology Applied in Food Science: A Review[J]. International Journal of Food Science and Technology, 2024.
[16] Liu B,Wu Y,Wang Y,et al.NF-kappaB p65 Knock-down inhibits TF,PAI-1 and promotes activated protein C production in lipopolysaccharide- stimulated alveolar epithelial cells type II[J].Exp Lung Res,2018,44(4- 5):241-251.
[17] Pandey P, Ganeshan S, Rajotiya S, et al. Deciphering the Anticancer Efficacy of Oroxylin A Targeting Dysregulated Oncogenes[J]. Current Gene Therapy, 2025.
[18] Zhang H, Cai J, Li C, et al. Wogonin inhibits latent HIV-1 reactivation by downregulating histone crotonylation[J]. Phytomedicine, 2023, 116:154855.
[19] Naeem H, Shahbaz M, Momal U, et al. Anticancer Potential of Wogonin: A Comprehensive Treatise[J]. Food Science & Nutrition, 2025, 13:e71128.
[20] Mao H, Zhao X, Sun S C. NF-κB in inflammation and cancer[J]. Cellular & Molecular Immunology, 2025, 22:811-839.
[21] Hong Y, Fu Y, Long Q. Post-translational governance of NF-κB in cancer immunity: mechanisms and therapeutic horizons[J]. Frontiers in Immunology, 2025, 16:1627084.
[22] Cao M, Day A M, Galler M, et al. A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms[J]. Molecular Cell, 2023, 83:3140-3154.
[23] Ge J, Yang H, Zeng Y, et al. Protective effects of wogonin on lipopolysaccharide-induced inflammation and apoptosis of lung epithelial cells and its possible mechanisms[J]. BioMedical Engineering OnLine, 2021, 20:125.
[24] Bai F, Chen Z, Xu S, et al. Wogonin attenuates neutrophilic inflammation and airway smooth muscle proliferation through inducing caspase-dependent apoptosis and inhibiting MAPK/Akt signaling in allergic airways[J]. International Immunopharmacology, 2022, 113:109410.
[25] Ge J, Yang H, Yu N, et al. Wogonin alleviates sepsis-induced acute lung injury by modulating macrophage polarization through the SIRT1-FOXO1 pathways[J]. Tissue and Cell, 2024, 88:102400.