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Halofuginone hydrobromide (HF), a bioactive compound derived from the Chinese herbal plant <jats:italic>Dichroa febrifuga<\/jats:italic> Lour., has demonstrated substantial anti-arthritic effects in RA. Nevertheless, the molecular mechanisms responsible for the anti-RA effects of HF remain unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This study employed a combination of network pharmacology, molecular docking, and experimental validation to investigate potential targets of HF in RA.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Network pharmacology analyses identified 109 differentially expressed genes (DEGs) resulting from HF treatment in RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses unveiled a robust association between these DEGs and the IL-17 signaling pathway. Subsequently, a protein-protein interaction (PPI) network analysis revealed 10 core DEGs, that is, EGFR, MMP9, TLR4, ESR1, MMP2, PPARG, MAPK1, JAK2, STAT1, and MAPK8. Among them, MMP9 displayed the greatest binding energy for HF. In an in vitro assay, HF significantly inhibited the activity of inflammatory macrophages, and regulated the IL-17 signaling pathway by decreasing the levels of IL-17\u00a0C, p-NF-\u03baB, and MMP9.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In summary, these findings suggest that HF has the potential to inhibit the activation of inflammatory macrophages through its regulation of the IL-17 signaling pathway, underscoring its potential in the suppression of immune-mediated inflammation in RA.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12906-024-04397-2","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T14:02:14Z","timestamp":1709042534000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of IL-17 signaling in macrophages underlies the anti-arthritic effects of halofuginone hydrobromide: Network pharmacology, molecular docking, and experimental validation"],"prefix":"10.1186","volume":"24","author":[{"given":"Junping","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaming","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoli","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"4397_CR1","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.autrev.2016.03.003","volume":"15","author":"P Conigliaro","year":"2016","unstructured":"Conigliaro P, Chimenti M, Triggianese P, Sunzini F, Novelli L, Perricone C, Perricone R. 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