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The synthetic cardiotonic steroid \u03b3-Benzylidene Digoxin 8 (BD-8) is emerging as a promising immunomodulatory molecule, although it has remained largely unexplored. Therefore, we tested the immunomodulatory potential of BD-8 both in vitro and in vivo. Hence, primary mouse macrophages were incubated with combinations of BD-8 and the pro-inflammatory fungal protein zymosan (ZYM). Nitric oxide (NO) production was determined by Griess reagent and cytokines production was assessed by enzyme-linked immunosorbent assay. Inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS), p-nuclear factor kappa B p65 (NF-\u03baB p65), p-extracellular signal-regulated kinase (p-ERK), and p-p38 were evaluated by flow cytometry. Macrophages exposed to BD-8 displayed reduced phagocytic activity, NO levels, and production of the proinflammatory cytokine IL-1\u03b2 induced by ZYM. Furthermore, BD-8 diminished the expression of iNOS and phosphorylation of NF-\u03baB p65, ERK, and p38. Additionally, BD-8 exhibited anti-inflammatory capacity in vivo in a carrageenan-induced mouse paw edema model. Taken together, these findings demonstrate the anti-inflammatory activity of BD-8 and further reinforce the potential of cardiotonic steroids and their derivatives as immunomodulatory molecules.<\/jats:p>","DOI":"10.3390\/cells13181568","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T09:43:13Z","timestamp":1726652593000},"page":"1568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Evaluation of Anti-Inflammatory Activity of the New Cardiotonic Steroid \u03b3-Benzylidene Digoxin 8 (BD-8) in Mice"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5262-6262","authenticated-orcid":false,"given":"Davi Azevedo","family":"Ferreira","sequence":"first","affiliation":[{"name":"Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraiba, Jo\u00e3o Pessoa 58.051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Beatriz Araujo","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraiba, Jo\u00e3o Pessoa 58.051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7333-1914","authenticated-orcid":false,"given":"Mariana Mendon\u00e7a","family":"Soares","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraiba, Jo\u00e3o Pessoa 58.051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9ssia de Almeida","family":"Lima","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraiba, Jo\u00e3o Pessoa 58.051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3384-5275","authenticated-orcid":false,"given":"Gabriela Carolina Santos Lima de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraiba, Jo\u00e3o Pessoa 58.051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateus Bernardo da Silva","family":"Leite","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraiba, Jo\u00e3o Pessoa 58.051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus Vieira","family":"Machado","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biochemistry, Campus Centro-Oeste Dona Lind\u00fa, Federal University of S\u00e3o Jo\u00e3o del-Rei, Divin\u00f3polis 35.501-296, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1580-0644","authenticated-orcid":false,"given":"Jos\u00e9 Augusto Ferreira Perez","family":"Villar","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biochemistry, Campus Centro-Oeste Dona Lind\u00fa, Federal University of S\u00e3o Jo\u00e3o del-Rei, Divin\u00f3polis 35.501-296, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro Augusto","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biochemistry, Campus Centro-Oeste Dona Lind\u00fa, Federal University of S\u00e3o Jo\u00e3o del-Rei, Divin\u00f3polis 35.501-296, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristoforo","family":"Scavone","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropharmacology Research, Department of Pharmacology, Institute of Biomedical Sciences ICB-1, University of 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