[Investigating on mechanism of Yangyin Yifei Tongluo Pills in improving idiopathic pulmonary fibrosis based on bioinformatics and machine learning combined with UHPLC-Q Exactive Orbitrap-HRMS].

Authors

Ke-Han Wen, Qi Zhao, Ao-Jie Guo, Zhi-Chao Wu, Xiao-Lin Xia, Le-le Chen, Yong Xu, Na Xiao

Published in

Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. Volume 51. Issue 11. Pages 3067-3079.

Abstract

Idiopathic pulmonary fibrosis(IPF) is a fatal interstitial lung disease with limited clinical therapeutic options. Traditional Chinese medicine formulas, characterized by multi-component, multi-target, and holistic regulatory properties, have shown unique potential in the prevention and treatment of IPF. Yangyin Yifei Tongluo Pills(YF) is a TCM formula with demonstrated clinical efficacy. However, its modern pharmacological mechanism against IPF remains to be systematically elucidated. In this study, ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-HRMS) was employed to identify the chemical constituents of YF. A total of 76 potential bioactive compounds were characterized, including flavonoids, phenylpropanoids and other chemicals. By integrating network pharmacology and bioinformatics analyses, drug-related targets, IPF-associated targets, differentially expressed genes, and WGCNA-derived key module genes were intersected, yielding 15 potential targets. Based on a systematic evaluation using nine machine learning algorithms, arginase 1(ARG1) and matrix metalloproteinase 14(MMP14) were identified as key core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses indicated that these targets were mainly involved in inflammatory regulation, signal transduction, and extracellular matrix(ECM) remodeling, with significant enrichment in key signaling pathways such as the TNF signaling pathway. Immune microenvironment analysis revealed that the expression levels of ARG1 and MMP14 were closely associated with immune and stromal cell infiltration characteristics. Molecular docking demonstrated favorable binding affinities between ARG1/MMP14 and several core components, including miltirone, peimine, cryptotanshinone, and sec-O-glucosylhamaudol, while molecular dynamics simulations further confirmed the conformational stability of miltirone and sec-O-glucosylhamaudol, as core potential bioactive components, with the targets under dynamic conditions. Collectively, these findings suggest that YF may exert anti-IPF effects by targeting ARG1 and MMP14 through its core potential bioactive components, synergistically modulating key processes including the immune microenvironment, fibroblast activation, and extracellular matrix remodeling. By integrating LC-MS, bioinformatics, machine learning, immune infiltration analysis, molecular docking, and molecular dynamics simulation, this study systematically elucidates the multi-component and multi-target mechanisms of YF, providing new insights and a foundation for the intervention and treatment of IPF and the mechanistic study of TCM formulas.

PMID:
42543268
Bibliographic data and abstract were imported from PubMed on 03 Aug 2026.

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