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a bis-indole alkaloid isolated from Caulerpa racemosa, has several documented pharmacological activities, including antineoplastic and antiviral properties. This study aimed to evaluate the anti-inflammatory and anti-tubercular potentials of caulerpin and its analogues in RAW 264.7 macrophages infected with Mycobacterium spp. Additionally, we evaluated cytokine production and NLRP3 expression in this infection model. Toxicity tests were performed using Vero E6 and HepG2 cell lines and Artemia salina. Pre-incubation of RAW 264.7 cells with caulerpin and its analogues decreased internalized M. smegmatis and M. tuberculosis H37Ra. Furthermore, treatment of M. smegmatis-infected macrophages with caulerpin and its analogues reduced bacterial loads. Caulerpin reduced the CFU count of internalized bacilli in the M. tuberculosis H37Ra infection model. In addition, caulerpin and its diethyl derivative were notably found to modulate IL-1\u03b2 and TNF-\u03b1 production in the M. smegmatis infection model after quantifying pro-inflammatory cytokines and NLRP3. Caulerpin and its derivates did not affect the viability of Vero E6 and HepG2 cell lines or nauplii survival in toxicity studies. These findings demonstrate that caulerpin and its analogues exhibit anti-inflammatory activity against Mycobacterium spp. infection in RAW 264.7 macrophages and show promising potential for further efficacy and safety evaluation.<\/jats:p>","DOI":"10.3390\/microorganisms13030561","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T09:04:49Z","timestamp":1740992689000},"page":"561","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Host-Mediated Antimicrobial Effects and NLRP3 Inflammasome Modulation by Caulerpin and Its Derivatives in Macrophage Models of Mycobacterial Infections"],"prefix":"10.3390","volume":"13","author":[{"given":"Maria Gabriella S.","family":"Sidr\u00f4nio","sequence":"first","affiliation":[{"name":"Postgraduate Program in Development and Technological Innovation in Medicines, Federal University of Para\u00edba (UFPB), Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eug\u00eania G.","family":"Freitas","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology in Microorganisms, Biotechnology Center, Federal University of Para\u00edba (UFPB), Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2198-1867","authenticated-orcid":false,"given":"Daniel W. A.","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Para\u00edba (UFPB), Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6987-262X","authenticated-orcid":false,"given":"Deyse C. M.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Para\u00edba (UFPB), Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vin\u00edcius A. B.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Biotechnology Center, Federal University of Para\u00edba (UFPB), Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Caroline M. de Queiroz","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Unip\u00ea, Centro Universit\u00e1rio\u2014Cruzeiro do Sul Educacional, Jo\u00e3o Pessoa 58053-000, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela C.","family":"Paulino","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology in Microorganisms, Biotechnology Center, Federal University of Para\u00edba (UFPB), Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela C.","family":"Borges","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology in Microorganisms, Biotechnology Center, Federal University of Para\u00edba (UFPB), Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaelle L.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology in Microorganisms, Biotechnology Center, Federal University of Para\u00edba (UFPB), Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7131-6414","authenticated-orcid":false,"given":"Nat\u00e1lia Ferreira de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural and Synthetic Bioactive Products, Department of Pharmaceutical Sciences, Federal University of Para\u00edba (UFPB), Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4863-8057","authenticated-orcid":false,"given":"Marcus T.","family":"Scotti","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural and Synthetic Bioactive Products, Department of Pharmaceutical Sciences, Federal University of Para\u00edba (UFPB), Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7320-7203","authenticated-orcid":false,"given":"Dem\u00e9trius A. 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