Ardisia japonica (Thunb.) Blume and Lespedeza cuneata G. Don may treat chronic obstructive pulmonary disease by targeting HK2 and PTAFR

IntroductionPrevious studies have demonstrated the significant efficacy of Ardisia japonica (Thunb.) Blume (Zijinniu) and Lespedeza cuneata G. Don (Tiesaozhou) in alleviating cough and reducing phlegm. This study employed network pharmacology and bioinformatics approaches to identify key genes assoc...

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Main Authors: Xian Luo, Zheng Hang Ge, Shan Luo, Bo Li, Xun Zhou, Yi Yang, Yong Jiang, Tao Tan, Ke Lin Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2025.1527632/full
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author Xian Luo
Zheng Hang Ge
Shan Luo
Bo Li
Xun Zhou
Yi Yang
Yong Jiang
Tao Tan
Ke Lin Wang
author_facet Xian Luo
Zheng Hang Ge
Shan Luo
Bo Li
Xun Zhou
Yi Yang
Yong Jiang
Tao Tan
Ke Lin Wang
author_sort Xian Luo
collection DOAJ
description IntroductionPrevious studies have demonstrated the significant efficacy of Ardisia japonica (Thunb.) Blume (Zijinniu) and Lespedeza cuneata G. Don (Tiesaozhou) in alleviating cough and reducing phlegm. This study employed network pharmacology and bioinformatics approaches to identify key genes associated with Zijinniu and Tiesaozhou in chronic obstructive pulmonary disease (COPD), offering insights into potential therapeutic strategies.MethodsData on COPD, along with the active ingredients and target genes of Zijinniu and Tiesaozhou, were utilized. By integrating the results of differential expression analysis and the target genes of these two plants, candidate genes were identified. Key genes were then confirmed through gene expression analysis in the GSE124180 and GSE42057 datasets. A nomogram was constructed based on these genes to assess COPD risk, followed by validation. Additionally, functional analysis, immune factor profiling, molecular docking, and reverse transcription-polymerase chain reaction (RT-qPCR) were performed.ResultsHK2 and PTAFR emerged as critical genes for COPD treatment, exhibiting significantly elevated expression in COPD samples. RT-qPCR confirmed the significantly higher expression of HK2 (P = 0.0425) in COPD samples. These findings highlight the potential of HK2 and PTAFR as therapeutic targets for COPD. Functional analysis further indicated that HK2 and PTAFR were co-enriched in pathways such as the “chemokine signaling pathway” and “FC gamma R-mediated phagocytosis,” suggesting their involvement in immune responses. Immune factor analysis revealed strong correlations between these genes and various chemotactic factors (e.g., CCL23, CCL5), immunosuppressants (e.g., IDO1, CSF1R), immunostimulants (e.g., ICOS, CD28), chemokine receptors (e.g., CXCR1, CXCR2), and major histocompatibility complex (MHC) molecules (e.g., HLA-B). Molecular docking revealed favorable binding energies between HK2 and quercetin (−8.2 kcal/mol), and between PTAFR and daucosterol (−8.4 kcal/mol), suggesting their potential as effective compounds targeting key genes for COPD therapy.ConclusionHK2 and PTAFR were identified as crucial genes in COPD, providing a solid theoretical foundation for future treatment strategies.
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spelling doaj-art-752f6b2472d44f57844cbb15cea7eadd2025-08-20T02:11:29ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-05-011210.3389/fmed.2025.15276321527632Ardisia japonica (Thunb.) Blume and Lespedeza cuneata G. Don may treat chronic obstructive pulmonary disease by targeting HK2 and PTAFRXian Luo0Zheng Hang Ge1Shan Luo2Bo Li3Xun Zhou4Yi Yang5Yong Jiang6Tao Tan7Ke Lin Wang8The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaThe Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaThe Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaThe Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaThe Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaThe Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaGuizhou Provincial Staff Hospital, Guiyang, Guizhou, ChinaThe Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaThe Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, ChinaIntroductionPrevious studies have demonstrated the significant efficacy of Ardisia japonica (Thunb.) Blume (Zijinniu) and Lespedeza cuneata G. Don (Tiesaozhou) in alleviating cough and reducing phlegm. This study employed network pharmacology and bioinformatics approaches to identify key genes associated with Zijinniu and Tiesaozhou in chronic obstructive pulmonary disease (COPD), offering insights into potential therapeutic strategies.MethodsData on COPD, along with the active ingredients and target genes of Zijinniu and Tiesaozhou, were utilized. By integrating the results of differential expression analysis and the target genes of these two plants, candidate genes were identified. Key genes were then confirmed through gene expression analysis in the GSE124180 and GSE42057 datasets. A nomogram was constructed based on these genes to assess COPD risk, followed by validation. Additionally, functional analysis, immune factor profiling, molecular docking, and reverse transcription-polymerase chain reaction (RT-qPCR) were performed.ResultsHK2 and PTAFR emerged as critical genes for COPD treatment, exhibiting significantly elevated expression in COPD samples. RT-qPCR confirmed the significantly higher expression of HK2 (P = 0.0425) in COPD samples. These findings highlight the potential of HK2 and PTAFR as therapeutic targets for COPD. Functional analysis further indicated that HK2 and PTAFR were co-enriched in pathways such as the “chemokine signaling pathway” and “FC gamma R-mediated phagocytosis,” suggesting their involvement in immune responses. Immune factor analysis revealed strong correlations between these genes and various chemotactic factors (e.g., CCL23, CCL5), immunosuppressants (e.g., IDO1, CSF1R), immunostimulants (e.g., ICOS, CD28), chemokine receptors (e.g., CXCR1, CXCR2), and major histocompatibility complex (MHC) molecules (e.g., HLA-B). Molecular docking revealed favorable binding energies between HK2 and quercetin (−8.2 kcal/mol), and between PTAFR and daucosterol (−8.4 kcal/mol), suggesting their potential as effective compounds targeting key genes for COPD therapy.ConclusionHK2 and PTAFR were identified as crucial genes in COPD, providing a solid theoretical foundation for future treatment strategies.https://www.frontiersin.org/articles/10.3389/fmed.2025.1527632/fullchronic obstructive pulmonary diseaseactive ingredientsnetwork pharmacologyHK2PTAFR
spellingShingle Xian Luo
Zheng Hang Ge
Shan Luo
Bo Li
Xun Zhou
Yi Yang
Yong Jiang
Tao Tan
Ke Lin Wang
Ardisia japonica (Thunb.) Blume and Lespedeza cuneata G. Don may treat chronic obstructive pulmonary disease by targeting HK2 and PTAFR
Frontiers in Medicine
chronic obstructive pulmonary disease
active ingredients
network pharmacology
HK2
PTAFR
title Ardisia japonica (Thunb.) Blume and Lespedeza cuneata G. Don may treat chronic obstructive pulmonary disease by targeting HK2 and PTAFR
title_full Ardisia japonica (Thunb.) Blume and Lespedeza cuneata G. Don may treat chronic obstructive pulmonary disease by targeting HK2 and PTAFR
title_fullStr Ardisia japonica (Thunb.) Blume and Lespedeza cuneata G. Don may treat chronic obstructive pulmonary disease by targeting HK2 and PTAFR
title_full_unstemmed Ardisia japonica (Thunb.) Blume and Lespedeza cuneata G. Don may treat chronic obstructive pulmonary disease by targeting HK2 and PTAFR
title_short Ardisia japonica (Thunb.) Blume and Lespedeza cuneata G. Don may treat chronic obstructive pulmonary disease by targeting HK2 and PTAFR
title_sort ardisia japonica thunb blume and lespedeza cuneata g don may treat chronic obstructive pulmonary disease by targeting hk2 and ptafr
topic chronic obstructive pulmonary disease
active ingredients
network pharmacology
HK2
PTAFR
url https://www.frontiersin.org/articles/10.3389/fmed.2025.1527632/full
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