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This study evaluated the effect of HCA in the rat model of arthritis induced by zymosan in the tibiotarsal joint and the involvement of macrophage-derived mediators. In vitro, macrophages were stimulated with zymosan before being incubated with HCA and the supernatant was injected into the joint. In vivo, HCA was administered by intravenous route after intra-articular injection of zymosan, fMLP, or macrophages supernatant. Hypernociception, edema and leukocyte influx were evaluated in the joints, and inflammatory mediators in the macrophage supernatant or periarticular tissue. In vitro, HCA (100\u00a0\u00b5g\/ml) reduced NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    and IL-1\u03b2 in the supernatant of macrophages. In vivo, HCA (3\u00a0mg\/kg) reduced articular hypernociception, edema and leukocyte influx elicited by zymosan, fMLP or by the supernatant of zymosan activated macrophages, as well as the zymosan-induced rolling and adhesion, and gene expression of iNOS and IL-1. HCA attenuated edema and leukocyte influx in the periarticular tissue, revealing preserved chondrocytes in the cartilage. In conclusion, HCA exerts anti-inflammatory effect in the arthritis induced by zymosan in rat tibio-tarsal joints, involving NO and IL-1 released by resident macrophages.\n                  <\/jats:p>","DOI":"10.1007\/s10719-026-10221-5","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T09:39:20Z","timestamp":1782121160000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophage modulation accounts for the anti-inflammatory effect of Hypnea cervicornis agglutinin in rat arthritis induced by zymosan"],"prefix":"10.1007","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2481-5733","authenticated-orcid":false,"given":"Francisco Glerison","family":"da Silva Nascimento","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6278-2755","authenticated-orcid":false,"given":"Pedro Henrique","family":"de Souza Ferreira Bringel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5226-2858","authenticated-orcid":false,"given":"Diego Freitas","family":"de Araujo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3778-0584","authenticated-orcid":false,"given":"M\u00e1rio Rog\u00e9rio Lima","family":"Mota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6966-8840","authenticated-orcid":false,"given":"Maria Gleiciane","family":"de Queiroz Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7420-5306","authenticated-orcid":false,"given":"Mayara Torquato Lima","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1865-2915","authenticated-orcid":false,"given":"Clareane Avelino Simpl\u00edcio","family":"Nobre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5791-6170","authenticated-orcid":false,"given":"Benildo Sousa","family":"Cavada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2220-4552","authenticated-orcid":false,"given":"Kyria Santiago","family":"do Nascimento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9399-4109","authenticated-orcid":false,"given":"Rondinelle Ribeiro","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2323-5385","authenticated-orcid":false,"given":"Ana Maria Sampaio","family":"Assreuy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"10221_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-018-0016-9","volume":"6","author":"Q Guo","year":"2018","unstructured":"Guo, Q., Wang, Y., Xu, D., Nossent, J., Pavlos, N.J., Xu, J.: Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. 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