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Published in: BMC Complementary Medicine and Therapies 1/2023

Open Access 01-12-2023 | Research

Exploration of the mechanism by which Huangqi Guizhi Wuwu decoction inhibits Lps-induced inflammation by regulating macrophage polarization based on network pharmacology

Authors: Sutong Wang, Tianshu Ji, Lin Wang, Yiwei Qu, Xinhui Wang, Wenting Wang, Mujie Lv, Yongcheng Wang, Xiao Li, Ping Jiang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2023

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Abstract

Background

Huangqi Guizhi Wuwu decoction (HQGZWWD) is a traditional Chinese herbal medicine formulation with significant anti-inflammatory activity. However, its underlying mechanism remains unknown. Through network pharmacology and experimental validation, this study aimed to examine the potential mechanism of HQGZWWD in regulating macrophage polarization and inflammation.

Methods

The active components were obtained from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP), whereas the corresponding targets were obtained from the TCMSP and Swiss Target Prediction database. The GeneCards database identified targets associated with macrophage polarization and inflammation. Multiple networks were developed to identify the key compounds, principal biological processes, and pathways of HQGZWWD that regulate macrophage polarization and inflammation. Autodock Vina is utilized to assess the binding ability between targets and active compounds. Finally, confirm the experiment’s central hypothesis. Human histiocytic lymphoma (U-937) cells were transformed into M1 macrophages following stimulation with Lipopolysaccharide (LPS) to evaluate the effect of HQGZWWD drug-containing mouse serum (HQGZWWD serum) on regulating macrophage polarization and inflammation.

Results

A total of 54 active components and 859 HQGZWWD targets were obtained. There were 9972 targets associated with macrophage polarization and 11,109 targets associated with inflammation. After screening, 34 overlapping targets were identified, of which 5 were identified as central targets confirmed by experiments, including the α7 nicotinic acetylcholine receptor (α7 nAchR), interleukin 6 (IL-6), Interleukin-1 beta (IL-1β), interleukin 10 (IL-10) and growth factor beta (TGF-β1). Pathway enrichment analysis revealed that 34 overlapping targets were enriched in multiple pathways associated with macrophage polarization and inflammation, including the TGF beta signaling pathway, NF-kappa B signaling pathway, JAK-STAT signaling pathway, and TNF signaling pathway. Molecular docking confirmed that the majority of HQGZWWD’s compounds can bind to the target. In vitro experiments, HQGZWWD serum was shown to up-regulate the expression of α7 nAchR, reduce the number of M1 macrophages, stimulate the production of M2 macrophages, inhibit the expression of pro-inflammatory cytokines IL-6 and IL1-β, and increase the expression of anti-inflammatory cytokines IL-10 and TGF-β1.

Conclusion

HQGZWWD can regulate the number of M1/M2 macrophages and the level of inflammatory cytokines, and the underlying mechanism may be related to the up-regulation of α7 nAchR expression.
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Metadata
Title
Exploration of the mechanism by which Huangqi Guizhi Wuwu decoction inhibits Lps-induced inflammation by regulating macrophage polarization based on network pharmacology
Authors
Sutong Wang
Tianshu Ji
Lin Wang
Yiwei Qu
Xinhui Wang
Wenting Wang
Mujie Lv
Yongcheng Wang
Xiao Li
Ping Jiang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2023
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-022-03826-4

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