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Journal of Traditional Chinese Medicine >

2024 , Vol. 44 >Issue 4: 770 - 783

DOI: https://doi.org/10.19852/j.cnki.jtcm.20240610.002

Original articles

Uncovering the action mechanism of Shenqi Tiaoshen formula (参芪调肾方) in the treatment of chronic obstructive pulmonary disease through network pharmacology, molecular docking, and experimental verification

  • Qinjun YANG ,
  • Dandan YIN ,
  • Hui WANG ,
  • Yating GAO ,
  • Xinheng WANG ,
  • Di WU ,
  • Jiabing TONG ,
  • Chuanbo WANG ,
  • Zegeng LI
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  • 1 School of Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230038, China
    2 Anhui Province Key Laboratory of the Application and Transformation of Traditional Chinese Medicine in the Prevention and Treatment of Major Pulmonary Diseases, Hefei 230031, China
    3 Department of Pharmacy, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
    4 Institute of Traditional Chinese Medicine Respiratory Disease Prevention and Control, Anhui Academy of Traditional Chinese Medicine, Hefei 230031, China
    5 Department of Respiratory, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
    6 Department of Chinese Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China

Received date: 2023-02-22

  Accepted date: 2023-06-15

  Online published: 2024-06-10

Supported by

Joint Key Project of the National Natural Science Foundation of China: the Molecular Mechanism Research on Xin'an Medical's Syndrome Differentiation of "Guben Peiyuan" in Improving Self-Perception of Chronic Obstructive Pulmonary Disease (COPD) Patients by the Regulation of Inflammation-Immunity Network(U20A20398);Major Science and Technology Project of Anhui Province: Development of a Comprehensive Management Platform for COPD based on Cloud Data and Research on the Promotion of Traditional Chinese Medicine Techniques(201903a0702015);Collaborative Innovation Project of Public Health in Provincial Medical Colleges: Research on the Intervention Mechanisms and Product Development of Xinan Medical's “Guben Peiyuan” Method and “Yangyin Tongluo” Method for Major Chronic Diseases based on Evidence-based Medicine Evaluation(GXXT-2020-025)

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Abstract

OBJECTIVE: To reveal the potential underlying mechanism of the Shenqi Tiaoshen formula (参芪调肾方, SQTS) in the treatment of chronic obstructive pulmonary disease (COPD) by utilizing network pharmacology, molecular docking, and experimental verification.

METHODS: Multiple open-source databases and research related to Traditional Chinese Medicine or compounds were employed to screen active ingredients and corresponding potential targets of the SQTS. The protein-protein interaction network screened hub genes, the relevant molecular mechanism and gene regulation were initially identified through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, and molecular docking was used to confirm further the interaction of the main components bound to the core targets. In vivo experiments on the COPD combined Qi-deficiency syndrome rat model were performed to verify the intervention effects and predicted potential molecular mechanisms of the SQTS.

RESULTS: This study selected 156 active compounds and 326 candidate targets for treating COPD. Quercetin, Nobiletin, Kaempferol, Luteolin, Ginsenoside Rh2 and Formononetin were probably the main active compounds of SQTS in COPD treatment as they affected the most COPD-related targets, and interleukin-1 (IL-6), signal transducing activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP9), vascular endothelial growth factor A (VEGFA), protein kinase B (AKT1), hypoxia-inducible factor-1α (HIF-1α), and forkhead box O3 (FoxO3) were identified as the hub genes associated with its therapeutic effect. KEGG analysis was mainly enriched in the signaling pathways closely related to inflammation, immunity and oxidative stress, such as HIF-1, tumor necrosis factor (TNF), phosphatidylinositol 3 kinase (PI3K)-AKT, FoxO, apoptosis, IL-17, and toll-like receptor. Molecular docking confirmed that the main active components shared a good affinity with the hub genes. In vivo experiments, the SQTS was found to improve the body weight, exhaustive swimming time, tail-hanging immobility time and struggle times, airway inflammation, lung functions, and inflammatory factors in the rat model of COPD. The up-regulation of p-PI3K, p-AKT, HIF-1α, FoxO3α, toll like receptor 4, VEGFA, Caspase 3, TNF-α, and IL-17 in COPD rats were down-regulated by SQTS, consistent with the network pharmacology results.

CONCLUSIONS: This study provides evidence that the SQTS plays a critical role in anti-inflammation via suppressing immune inflammation and oxidative stress related pathways, indicating that the SQTS is a candidate herbal drug for further investigation in treating COPD.

Key words： pulmonary disease, chronic obstructive; inflammation; network pharmacology; molecular docking simulation; experimental validation; Shenqi Tiaoshen formula

Cite this article

Qinjun YANG , Dandan YIN , Hui WANG , Yating GAO , Xinheng WANG , Di WU , Jiabing TONG , Chuanbo WANG , Zegeng LI . Uncovering the action mechanism of Shenqi Tiaoshen formula (参芪调肾方) in the treatment of chronic obstructive pulmonary disease through network pharmacology, molecular docking, and experimental verification[J]. Journal of Traditional Chinese Medicine, 2024 , 44(4) : 770 -783 . DOI: 10.19852/j.cnki.jtcm.20240610.002

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