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Journal of Traditional Chinese Medicine >

2024 , Vol. 44 >Issue 4: 784 - 793

DOI: https://doi.org/10.19852/j.cnki.jtcm.20240610.005

Original articles

Integration of serum pharmacochemistry with network pharmacology to reveal the potential mechanism of Yangqing Chenfei formula (养清尘肺方) for the treatment of silicosis

  • Yuanyuan HU ,
  • Xinguang LIU ,
  • Peng ZHAO ,
  • Jinyan WU ,
  • Xinhua YAN ,
  • Runsu HOU ,
  • Xiangcheng WANG ,
  • Fan YANG ,
  • Xinrong TIAN ,
  • Jiansheng LI
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  • 1 Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
    2 Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan and Education Ministry of P.R. China. Zhengzhou, 450046, China
    3 Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou 450046, China

Received date: 2022-11-22

  Accepted date: 2023-04-28

  Online published: 2024-06-10

Supported by

Special Project of Traditional Chinese Medicine Research in Henan Province: Evaluation and Characteristics of the Therapeutic Effect of Dialectical Treatment for Coal Worker Pneumoconiosis Based on Multicenter, Randomized, Double-Blind, and Parallel Controlled Trials(20-21ZYZD01)

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Abstract

OBJECTIVE: To explore the mechanisms of Yangqing Chenfei formula (养清尘肺方, YCF) in the treatment of silicosis through a comprehensive strategy consisting of serum pharmacochemistry, network pharmacology analysis, and in vitro validation.

METHODS: An ultrahigh-performance liquid chroma-tography-tandem mass spectrometry method was used to confirm the active components in YCF-medicated serum. Then, we obtained targets for active components and genes for silicosis from multiple databases. Furthermore, a protein-protein interaction network was constructed, and Kyoto Encyclopedia of Genes and Genomes pathway and biological process analyses were conducted to elucidate the mechanisms of YCF for the treatment of silicosis. Finally, we validated the important components and mechanisms in vitro.

RESULTS: Altogether, 19 active components were identified from rat serum after YCF administration. We identified 724 targets for 19 components, which were mainly related to inflammation [phosphatidy linositol 3 kinase/protein kinase B, forkhead box O, hypoxia inducible factor, and T-cell receptor signaling pathway, nitric oxide biosynthetic process], fibrotic processes [vascular endothelial growth factor signaling pathway, extracellular signal regulated kinase (ERK) 1 and ERK2 cascade, smooth muscle cell proliferation], and apoptosis (negative regulation of apoptotic process). In addition, 218 genes for silicosis were identified and were mainly associated with the inflammatory response and immune process [cytokine-cytokine receptor interaction, tumor necrosis factor alpha (TNF-α), toll-like receptor, and nucleotide binding oligomerization domain-like receptor signaling pathway]. Taking an intersection of active component targets and silicosis genes, we obtained 61 common genes that were mainly related to the inflammatory response and apoptosis, such as the phosphatidylinositol-3-kinase/protein kinase B signaling pathway, mitogen activated protein kinases signaling pathway, TNF signaling pathway, toll-like receptor signaling pathway, biosynthesis of nitric oxide, and apoptotic process. In the herb-component-gene-pathway network, paeoniflorin, rutin and nobiletin targeted the most genes. In vitro, paeoniflorin, rutin and nobiletin decreased the mRNA levels of inflammatory factors [interleukin (IL)-6, TNF-α, and IL-1β], suppressed p-AKT and cleaved caspase-3, and increased B cell lymphoma (Bcl)-2 protein expression in silica-induced macrophages in a concentration-dependent manner.

CONCLUSION: YCF could significantly relieve the inflammatory response of silicosis via suppression of the AKT/Bcl-2/Caspase-3 pathway.

Key words： silicosis; network pharmacology; validation study; serum pharmacochemistry; Yangqing Chenfei formula

Cite this article

Yuanyuan HU , Xinguang LIU , Peng ZHAO , Jinyan WU , Xinhua YAN , Runsu HOU , Xiangcheng WANG , Fan YANG , Xinrong TIAN , Jiansheng LI . Integration of serum pharmacochemistry with network pharmacology to reveal the potential mechanism of Yangqing Chenfei formula (养清尘肺方) for the treatment of silicosis[J]. Journal of Traditional Chinese Medicine, 2024 , 44(4) : 784 -793 . DOI: 10.19852/j.cnki.jtcm.20240610.005

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