{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:31:24Z","timestamp":1792704684459,"version":"4.5.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>The purpose of this research study was to investigate the impact of isoimperatorin on Aspergillus fumigatus (A. fumigatus) keratitis and elucidate its underlying mechanisms via the TLR4\/MyD88\/IKK\/NF-\u03baB signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      The targets of the active ingredient isoimperatorin were identified via network pharmacology. Key interactions between isoimperatorin and its predicted targets were validated using molecular docking.\n                      <jats:italic>In vitro<\/jats:italic>\n                      RAW264.7 macrophage cells of A. fumigatus keratitis, the effects of isoimperatorin on inflammatory signaling and cell apoptosis were assessed using western blotting, immunofluorescence, and flow cytometry.\n                      <jats:italic>In vivo<\/jats:italic>\n                      C57BL\/6 mouse models of A. fumigatus keratitis, the effects of isoimperatorin on inflammatory signaling, neutrophil infiltration, macrophage polarization, and cell apoptosis were assessed using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunofluorescence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Isoimperatorin inhibited TLR4\/MyD88 complex formation and IKK\/NF-\u03baB phosphorylation, downregulated pro-inflammatory cytokines, reduced neutrophil infiltration, and promoted macrophage polarization from the M1 to the M2 phenotype. Additionally, it inhibited cell apoptosis and alleviated corneal epithelial damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates that isoimperatorin exerts a protective effect against A. fumigatus keratitis primarily by modulating the host immune response. The mechanism is mediated through the multi-target inhibition of the TLR4\/MyD88\/IKK\/NF-\u03baB pathway, leading to a coordinated reduction in inflammation and tissue damage. These findings highlight the therapeutic potential of isoimperatorin as a novel immunomodulatory strategy for managing fungal keratitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1676397","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T05:25:10Z","timestamp":1769491510000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Isoimperatorin alleviates fungal keratitis by regulating NF-\u03baB pathway and macrophage immune response"],"prefix":"10.3389","volume":"17","author":[{"given":"Shiqi","family":"Song","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huirong","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Shandong University of Traditional Chinese 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