Molecular Mechanisms of Dachengqi Decoction in Acute Respiratory Distress Syndrome: A Network Pharmacology and Bioinformatics Analysis

Summary

This study elucidates the molecular mechanisms of Dachengqi Decoction (DCQD) against acute respiratory distress syndrome (ARDS) using network pharmacology, bioinformatics, and molecular docking. Key targets and pathways were identified. Molecular docking validated robust ligand-target interactions, supporting DCQD's multi-target therapeutic potential for ARDS.

Abstract

Acute respiratory distress syndrome (ARDS) is a life-threatening complication of sepsis, characterized by refractory hypoxemia and pulmonary inflammation. Currently, effective pharmacological interventions remain limited. Traditional Chinese medicine (TCM), exemplified by Dachengqi Decoction (DCQD), has demonstrated therapeutic potential in modulating complex inflammatory responses. To investigate the mechanism of DCQD in ARDS treatment, active components of DCQD and their associated targets were first retrieved from public databases. ARDS-related targets were identified through bioinformatics analysis of public datasets. By intersecting drug-specific targets with disease-related targets, a DCQD-ARDS interaction network was constructed using protein-protein interaction (PPI) analysis and functional enrichment. Comprehensive analysis revealed 32 overlapping genes critical to DCQD's therapeutic efficacy in ARDS. Enrichment analysis highlighted key pathways, including the chemokine signaling pathway, NOD-like receptor signaling, and neutrophil extracellular trap (NET) formation, which are implicated in immunomodulation and inflammation. The PPI network identified HSP90AB1, MMP9, HSP90AA1, ARG1, and MYC as core targets. Molecular docking confirmed strong binding affinities between these targets and DCQD components. Our findings untangle the mechanistic basis supporting DCQD as a promising adjunctive therapy for sepsis-induced ARDS.

Introduction

Acute respiratory distress syndrome (ARDS) is a highly heterogeneous clinical syndrome caused by various pulmonary or extrapulmonary factors, primarily characterized by diffuse lung injury and refractory hypoxemia¹. Since its first definition in 1967, the understanding of ARDS has continuously evolved, leading to iterative revisions of its diagnostic criteria². Furthermore, the implementation of therapeutic strategies, including lung-protective ventilation, ex vivo support, and prone positioning, has profoundly influenced both clinical management and research progress³. Nevertheless, ARDS....

Protocol

All materials, including databases, software, and experimental reagents, used in this study are listed in the Table of Materials. All experimental procedures were approved by the Animal Ethics Committee of the Suzhou Dushu Lake Hospital (permit number: 2410008).

Screening of active components and target acquisition of DCQD
The active components of the constituent herbs rhubarb, mirabilite, magnolia bark, and immature bitter orange in Da-Cheng-Qi Decoction (DCQD) were screened from the traditional Chinese medicine systems pharmacology (TCMSP) database using the following criteria: oral bioavailability ....

Results

Bioactivity analysis of DCQD
To untangle the molecular mechanisms underlying the bioactivity of DCQD, potential targets were first identified by screening the Swiss target prediction and TCMSP databases. A total of 16 components from rhubarb, 17 from immature bitter orange, and 2 from magnolia bark were matched, yielding 614 potential targets (Figure 1A). Subsequently, a network diagram was constructed to visualize the relationships among the three herbal medicines, thei.......

Discussion

ARDS has evolved into a life-threatening pulmonary disorder, imposing a substantial burden on global healthcare, with an annual incidence of 1.5-79 cases per 100,000 individuals and mortality rates ranging from 34.9% to 46.1% across varying severity levels³⁷. Despite advancements in mechanical ventilation strategies, including lung-protective ventilation and prone positioning, clinical outcomes remain suboptimal due to the heterogeneity of pathophysiological processes and limited therapeutic optio.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Arginase-1 Polyclonal antibody	Protein Tech Group Inc., USA	16001-1-AP
AutoDock	The Scripps Research Institute	NA	http://autodock.scripps.edu/
BATMAN-TCM database	Beijing University of Chinese Medicine	NA	http://bionet.ncpsb.org.cn/batman-tcm/
BCA protein quantification kit	Servicebio	G2026
Bioinformatics	Bioinformatics	NA	https://www.bioinformatics.com.cn/
BIO-RAD chemiluminescence imaging system	Thermo Fisher Scientific	https://www.bio-rad.com/en-in/category/chemidoc-imaging-systems?ID=NINJ0Z15
C57BL/6J mice	Hangzhou Ziyuan Laboratory Animal Technology Co., Ltd
c-MYC Polyclonal antibody	Protein Tech Group Inc., USA	10828-1-AP
Cytoscape	Cytoscape	version 3.10.3	https://cytoscape.org/
DCQD	The Traditional Chinese Medicine Department of Suzhou Dushu Lake Hospital
Discovery Studio Visualizer	Discovery	version 4.5
GraphPad Prism	Dotmatics	version10.1.2	https://www.graphpad.com/
GAPDH Polyclonal antibody	Protein Tech Group Inc., USA	10494-1-AP
Gel preparation kit	Servicebio	G2003
GeneCards  database	Crown human genome center	NA	https://previous.genecards.org/
GEO database	National Center for Biotechnology Information (NCBI)		GSE32707 (GPL570 platform, n=45)
HRP-conjugated Affinipure Goat Anti-Rabbit IgG(H+L)	Protein Tech Group Inc., USA	SA00001-2
HSP90 Polyclonal antibody	Protein Tech Group Inc., USA	13171-1-AP
Lipopolysaccharides(LPS)	Solarbio	L8880
Metascape database	NIH	NA	https://metascape.org/gp/index
Microplate reader	BioTeK	https://www.agilent.com/en/product/cell-analysis/microplate-readers?srs ltid=AfmBOoqJhJhNJW6vNU fnskFb9jjcTgXww1A1km-JVP P1SScq1Mx78HBi
MMP-9 (N-terminal) Polyclonal antibody	Protein Tech Group Inc., USA	10375-2-AP
Mouse IL-18 ELISA Kit	Servicebio	GEH0010
Mouse IL-6 ELISA Kit	Servicebio	GEM0001
Mouse TNF-alpha ELISA Kit	Servicebio	GEH0004
OMIM database	Johns Hopkins University	NA	https://www.omim.org/
Omni-ECL™ Ultra-Sensitive Chemiluminescence Detection Kit	Epizyme Biotech	SQ201
PDB database	RCSB	NA	http://www.rcsb.org/
Protein-free rapid blocking buffer	Epizyme Biotech	G2052
PubChem database	National Center for Biotechnology Information (NCBI)		https://pubchem.ncbi.nlm.nih.gov/
PVDF membrane	Merck	NA
PyMOL	Schrodinger	version 3.10.3
STRING database	Global biodata coalition and Elixir	NA	https://cn.string-db.org/
Swiss Target Prediction database	Swiss Institute of Bioinformatics	NA	http://www.swisstargetprediction.cn/
Traditional Chinese Medicine Systems Pharmacology (TCMSP) database	Northwestern Polytechnical University	version 2.3	https://www.tcmsp-e.com/