Maria Rafaele Oliveira Bezerra da Silva, Ana Carla da Silva, Byannca de Carvalho Torreão, Romero Marcos Pedrosa Brandão Costa, Raquel Pedrosa Bezerra, Silvana de Fátima Ferreira da Silva, Maria Luiza Vilela Oliva, Lícya Samara da Silva Xavier, Isabelle F T Viana, Roberto Dias Lins, Virginia Maria Barros de Lorena, Daniela de Araújo Viana Marques
{"title":"平节螺旋体化合物对恰加斯病的治疗潜力和免疫调节特性。","authors":"Maria Rafaele Oliveira Bezerra da Silva, Ana Carla da Silva, Byannca de Carvalho Torreão, Romero Marcos Pedrosa Brandão Costa, Raquel Pedrosa Bezerra, Silvana de Fátima Ferreira da Silva, Maria Luiza Vilela Oliva, Lícya Samara da Silva Xavier, Isabelle F T Viana, Roberto Dias Lins, Virginia Maria Barros de Lorena, Daniela de Araújo Viana Marques","doi":"10.1021/acsinfecdis.4c01052","DOIUrl":null,"url":null,"abstract":"<p><p><i>Arthrospira platensis</i>, an ancient cyanobacterium, is rich in bioactive compounds with therapeutic potential, supporting its use in studies for various health conditions, including infectious and chronic diseases. This study aimed to evaluate the antiparasitic, cytotoxic, and immunomodulatory activities of <i>A. platensis</i> compounds against <i>Trypanosoma cruzi</i>. Peripheral Blood Mononuclear Cells (PBMC) and <i>T. cruzi</i> trypomastigotes were cultured for cytotoxic and antiparasitic analyses. Cytotoxicity was assessed in PBMC treated with different concentrations of crude extract, obtained by mechanical agitation in 0.1 M TRIS-HCl buffer (pH 7.2), and purified protein by DEAE-Sephadex A-50 chromatography and FPLC. Immune response was analyzed in infected and uninfected PBMC by measuring cytokines (IFN-γ, TNF, IL-2, IL-6, and IL-10) after treatment with purified protein and benznidazole. <i>In vitro</i> experiments showed that both crude extract and a 15 kDa purified protein were toxic to trypomastigotes in a dose-dependent manner, eliminating over 80% of the parasite at 1000 and 200 μg/mL, respectively. Both the extract and protein were nontoxic to PBMC, with the protein (SI: 20.7) being more selective than benznidazole (SI: 11.5). Results indicated that the purified protein modulated the immune response in <i>T. cruzi</i>-infected individuals, inducing a protective Th1 response while controlling an excessive inflammatory response with appropriate IL-10 levels. The anti-<i>T. cruzi</i> activity of this protein, alone or in combination with the commercial drug, suggests it could be a low-cost, safer, and more tolerable therapy for Chagas disease treatment.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.0000,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Therapeutical Potential and Immunomodulatory Profile of <i>Arthrospira platensis</i> Compounds against Chagas Disease.\",\"authors\":\"Maria Rafaele Oliveira Bezerra da Silva, Ana Carla da Silva, Byannca de Carvalho Torreão, Romero Marcos Pedrosa Brandão Costa, Raquel Pedrosa Bezerra, Silvana de Fátima Ferreira da Silva, Maria Luiza Vilela Oliva, Lícya Samara da Silva Xavier, Isabelle F T Viana, Roberto Dias Lins, Virginia Maria Barros de Lorena, Daniela de Araújo Viana Marques\",\"doi\":\"10.1021/acsinfecdis.4c01052\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Arthrospira platensis</i>, an ancient cyanobacterium, is rich in bioactive compounds with therapeutic potential, supporting its use in studies for various health conditions, including infectious and chronic diseases. This study aimed to evaluate the antiparasitic, cytotoxic, and immunomodulatory activities of <i>A. platensis</i> compounds against <i>Trypanosoma cruzi</i>. Peripheral Blood Mononuclear Cells (PBMC) and <i>T. cruzi</i> trypomastigotes were cultured for cytotoxic and antiparasitic analyses. Cytotoxicity was assessed in PBMC treated with different concentrations of crude extract, obtained by mechanical agitation in 0.1 M TRIS-HCl buffer (pH 7.2), and purified protein by DEAE-Sephadex A-50 chromatography and FPLC. Immune response was analyzed in infected and uninfected PBMC by measuring cytokines (IFN-γ, TNF, IL-2, IL-6, and IL-10) after treatment with purified protein and benznidazole. <i>In vitro</i> experiments showed that both crude extract and a 15 kDa purified protein were toxic to trypomastigotes in a dose-dependent manner, eliminating over 80% of the parasite at 1000 and 200 μg/mL, respectively. Both the extract and protein were nontoxic to PBMC, with the protein (SI: 20.7) being more selective than benznidazole (SI: 11.5). Results indicated that the purified protein modulated the immune response in <i>T. cruzi</i>-infected individuals, inducing a protective Th1 response while controlling an excessive inflammatory response with appropriate IL-10 levels. The anti-<i>T. cruzi</i> activity of this protein, alone or in combination with the commercial drug, suggests it could be a low-cost, safer, and more tolerable therapy for Chagas disease treatment.</p>\",\"PeriodicalId\":17,\"journal\":{\"name\":\"ACS Infectious Diseases\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-03-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Infectious Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1021/acsinfecdis.4c01052\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acsinfecdis.4c01052","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Therapeutical Potential and Immunomodulatory Profile of Arthrospira platensis Compounds against Chagas Disease.
Arthrospira platensis, an ancient cyanobacterium, is rich in bioactive compounds with therapeutic potential, supporting its use in studies for various health conditions, including infectious and chronic diseases. This study aimed to evaluate the antiparasitic, cytotoxic, and immunomodulatory activities of A. platensis compounds against Trypanosoma cruzi. Peripheral Blood Mononuclear Cells (PBMC) and T. cruzi trypomastigotes were cultured for cytotoxic and antiparasitic analyses. Cytotoxicity was assessed in PBMC treated with different concentrations of crude extract, obtained by mechanical agitation in 0.1 M TRIS-HCl buffer (pH 7.2), and purified protein by DEAE-Sephadex A-50 chromatography and FPLC. Immune response was analyzed in infected and uninfected PBMC by measuring cytokines (IFN-γ, TNF, IL-2, IL-6, and IL-10) after treatment with purified protein and benznidazole. In vitro experiments showed that both crude extract and a 15 kDa purified protein were toxic to trypomastigotes in a dose-dependent manner, eliminating over 80% of the parasite at 1000 and 200 μg/mL, respectively. Both the extract and protein were nontoxic to PBMC, with the protein (SI: 20.7) being more selective than benznidazole (SI: 11.5). Results indicated that the purified protein modulated the immune response in T. cruzi-infected individuals, inducing a protective Th1 response while controlling an excessive inflammatory response with appropriate IL-10 levels. The anti-T. cruzi activity of this protein, alone or in combination with the commercial drug, suggests it could be a low-cost, safer, and more tolerable therapy for Chagas disease treatment.
期刊介绍:
ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to:
* Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials.
* Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets.
* Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance.
* Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents.
* Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota.
* Small molecule vaccine adjuvants for infectious disease.
* Viral and bacterial biochemistry and molecular biology.