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- W4386740110 abstract "Abstract Backgrounds Zhizi Chuanxiong herb pair (ZCHP) can delay the pathological progression of atherosclerosis (AS). However, the exact pharmacological mechanism by ZCHP improves AS remain unclear due to the complexity of its components. Therefore, this study systematically elaborated the anti-AS mechanism of ZCHP. Methods The potential targets of ZCHP blood components were predicted by searching TCMSP, ETCM, BATMAN-TCM, STITCH and SwissTargetPrediction databases. Then, GEO database was used to search for disease targets associated with AS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis were performed by DAVID. Molecular docking was used to verify the binding of the core target with the blood components, and finally animal experiment was used to verify the mechanism of action. Results A ZCHP-components-targets-AS network was constructed using Cytoscape software, which included 16 main components and 58 candidate targets. Crucial genes, such as TNF, IL-1β, IGF1, MMP9, CCR5, HMOX1, PTGS1, SELE, ALOX5, and SYK were shown in PPI network. KEGG enrichment showed that TNF and NF-κB signaling pathway were put in an important position of the treatment. These results were validated by molecular docking method. In vivo, ZCHP significantly reduced pulse wave velocity, intima-media thickness, plaque area, and serum lipid levels, and increased difference between end-diastolic and end-systolic diameters in ApoE -/- mice. Meanwhile, ZCHP significantly decreased the mRNA and protein expression of TNF-α and IL-1β, suppressed NF-κB activation, and inhibited the M1 macrophage polarization marker CD86 in ApoE -/- mice. Conclusion This study combined network pharmacology, molecular biology and animal experiment to suggest that ZCHP could alleviate AS by suppressing TNF/NF-κB axis mediated M1 macrophage polarization." @default.
- W4386740110 created "2023-09-15" @default.
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- W4386740110 date "2023-09-14" @default.
- W4386740110 modified "2023-09-26" @default.
- W4386740110 title "Effects and mechanisms of Zhizi Chuanxiong herb pair against atherosclerosis: An integration of network pharmacology, molecular docking and experimental validation" @default.
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- W4386740110 doi "https://doi.org/10.21203/rs.3.rs-3326432/v1" @default.
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