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image of Exploring the Mechanism of Bu Zhong Yi Qi Decoction in Treating Sepsis-induced Acute Lung Injury based on Network Pharmacology and Experimental Verification

Abstract

Introduction

Sepsis-induced acute lung injury (S-ALI) is one of the diseases with a very high fatality rate. However, the traditional Chinese medicine compound Buzhong Yiqi Decoction (BZYQD) has an excellent effect in the treatment of S-ALI. Nevertheless, its mechanism of action is still unclear. In this study, we explored the molecular mechanisms of S-ALI injury treated with buzhong yiqi decoction through network pharmacology, in combination with in vivo experimental validation.

Methods

Traditional Chinese medicine system pharmacology (TCMSP) database was used to screen thechemical composition of BZYQD and its action targets; Multiple databases were used to collect target genesfor-S-ALI, including OMIM, TTD, GeneCards, and DrugBank; The STRING database was used for the protein-protein interaction (PPI) analysis of the common targets of the BZYQD and the S-ALI; The DAVID databasewas used for GO and KEGG analysis; molecular docking was used to detect the binding capacity of corecomponents and targets. HE staining was used to visualize the pathology of lung tissue in each group; ELISA wasused to detect the levels of inflammatory factors (IL-1β, IL-6, IL-8, NF-κB and TNF-α) and oxidative stressrelatedfactors (LDH, CK-MB, SOD, GSH-Px); The qPCR and Western blot were used to examine the mRNAand protein expression of IL-1β, IL-6, TNF-α NF-κB, p-NF-κB, PI3K, p-PI3K, AKT, and IKKα.

Results

113 chemical components and 226 targets were screened from BZYQD; 9059 S-ALI-related geneswere screened out, with a total of 228 intersecting targets between BZYQD and S-ALI. Stigmasterol, quercetin, and isorhamnetin are the core components of BZYQD, PPI analysis shows that AKT1, IL6, TNF, andIL1B are the core targets of BZYQD for treating S-ALI, and molecular docking results show that the corecomponents have high binding activity with the target; Enrichment analysis shows that these core targets arerelated to the TNF signaling pathway. In vivo experimental studies have found that BZYQD can improve thedegree of inflammatory infiltration and edema in lung tissue of S-ALI model mice, reduce the expression ofIL-6, IL-1β, IL-8, TNF-α, LDH, CK-MB, and NF-κB in serum (P0.05), as well as the mRNA and proteinexpression of IL-6, IL-1β, TNF-α, NF-κB, p-NF-κB, PI3K, p-PI3K, AKT, and IKKα in lung tissue (P0.05),and levels of SOD and GSH-Px were increased (P0.05).

Discussion

The action targets of the main chemical components of BZYQD are TNF, AKT, and IL6. Thesetargets can promote the activation of PI3K and TNF pathways and mediate the occurrence of inflammationand oxidative stress, which provides inspiration for the treatment of S-ALI. However, the results of this study still need to be verified in combination with in vitro approaches.

Conclusion

This study suggests that the mechanism of BZYQD in treating S-ALI may be achieved by inhibiting the TNF and PI3K signaling pathway and reducing inflammation and oxidative stress levels.

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2025-09-30
2025-11-04

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Exploring the Mechanism of Bu Zhong Yi Qi Decoction in Treating Sepsis-induced Acute Lung Injury based on Network Pharmacology and Experimental Verification
Bentham Science Publishers ; https://doi.org/10.2174/0113816128397243250902131510
/content/journals/cpd/10.2174/0113816128397243250902131510
/content/journals/cpd/10.2174/0113816128397243250902131510
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  • Article Type:     Research Article
Keywords: Network pharmacology ; Bu Zhong Yi Qi decoction ; KEGG analysis ; TNF signaling pathway ; sepsis acute lung injury, inflammation

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