Dataset Information

The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification.

ABSTRACT:

Context

Huangqi Guizhi Wuwu Decoction (HGWD) is effective in treating ischaemic stroke (IS). However, its mechanism of action is still unclear.

Objective

Network pharmacology integrated with in vivo experiments were used to clarify the underlying mechanisms of HGWD for treating IS.

Materials and methods

TCMSP, GeneCards, OMIM and STRING were used to retrieve and construct visual protein interaction networks for the key targets. The AutoDock tool was used for molecular docking between key targets and active compounds. The neuroprotective effect of HGWD were verified in a middle cerebral artery occlusion (MCAO) model rat. The Sprague-Dawley (SD) rats were divided into sham, model, low-dose (5 g/kg, i.g.), high-dose (20 g/kg, i.g.), and nimodipine (20 mg/kg, i.g.) groups once daily for 7 days. The neurological scores, brain infarct volumes, lipid peroxidation, inflammatory cytokines, Nissl bodies, apoptotic neurons, and signalling pathways were all investigated and evaluated in vivo.

Results

Network pharmacology identified 117 HGWD targets related to IS and 36 candidate compounds. GO and KEGG analyses showed that HGWD anti-IS effects were mainly associated with PI3K-Akt and HIF-1 signalling pathways. HGWD effectively reduced the cerebral infarct volumes (19.19%), the number of apoptotic neurons (16.78%), and the release of inflammatory cytokines, etc. in MCAO rats. Furthermore, HGWD decreased the levels of HIF-1A, VEGFA, Bax, cleaved caspase-3, p-MAPK1, and p-c-Jun while increasing the expression of p-PI3K, p-AKT1, and Bcl-2.

Discussion and conclusion

This study initially elucidated the mechanism of HGWD anti-IS, which contributed to the further promotion and secondary development of HGWD in clinical practice.

SUBMITTER: Liao W

PROVIDER: S-EPMC10327528 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification.

Liao Weiguo W Wang Minchun M Wu Ying Y Du Jinyan J Li Yaxin Y Su Anyu A Zhong Lanying L Xie Zi Z Gong Mingyu M Liang Junhui J Wang Pengcheng P Liu Zai Z Wang Lisheng L

Pharmaceutical biology 20231201 1

<h4>Context</h4>Huangqi Guizhi Wuwu Decoction (HGWD) is effective in treating ischaemic stroke (IS). However, its mechanism of action is still unclear.<h4>Objective</h4>Network pharmacology integrated with <i>in vivo</i> experiments were used to clarify the underlying mechanisms of HGWD for treating IS.<h4>Materials and methods</h4>TCMSP, GeneCards, OMIM and STRING were used to retrieve and construct visual protein interaction networks for the key targets. The AutoDock tool was used for molecula ...[more]

PMID: 37410583

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Project description:In this study, we predicted the core active compounds of Huangqi Guizhi Wuwu decoction in treatment of oxaliplatin-induced peripheral neuropathy and the related potential mechanism. Corresponding database was used to complete the interaction (PPI) network of key targets and the enrichment analysis of corresponding genmes. Molecular docking of key targets and key compounds was carried out using relevant software. The 60 chemical components corresponding to the oral absorption of Huangqi Guizhi Wuwu decoction correspond to 157 unique targets, and the 233 chemical components corresponding to percutaneous absorption in vitro correspond to 155 unique targets. There were 1074 unique targets for chemotherapy-induced peripheral neuropathy. Finally, three common key targets (SLC6A2, SLC6A3, and SLC6A4) and two key compounds (6-Gingerol and nuciferin) were screened according to the above three target datasets. The results showed that The PPI network of common key targets involved 23 associated proteins. In the related GO enrichment results, there were 33 items related to biological processes, 13 items related to cell composition, 21 items related to molecular function, and four KEGG pathway enrichments. L1000 kinase and GPCR perturbation analysis showed that the associated protein had an effect on the expression of multiple groups of kinase genes. HPA revealed that the enrichment of three common key targets was tissue-specific. The docking results showed that the 6 groups were structurally stable. The oral and topical use of Huangqi Guizhi Wuwu decoction can prevent and control peripheral neurotoxicity. The prevention and control effects may be related to its participation in the regulation of neurotransmitter transport, sympathetic activity, and transport. The histological parts of the mechanism are mainly distributed in the adrenal gland, placenta, brain, intestine, and lung, the blood is not specific. According to the prediction results of molecular docking, 6-Gingerol and nuciferin can closely bind to three common key targets.

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Project description:BackgroundHuangqi 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.MethodsThe 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.ResultsA 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.ConclusionHQGZWWD 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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Dataset Information

The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification.

Context

Objective

Materials and methods

Results

Discussion and conclusion

Publications

The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification.

Similar Datasets

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