Therapeutical Potential and Immunomodulatory Profile of Arthrospira platensis Compounds against Chagas Disease

IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL
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 and Daniela de Araújo Viana Marques*, 
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Abstract

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.

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
Arthrospira platensis是一种古老的蓝藻,富含具有治疗潜力的生物活性化合物,支持其在各种健康状况(包括传染病和慢性病)的研究中使用。摘要本研究旨在评价plata . ensis化合物对克氏锥虫的抗寄生、细胞毒和免疫调节活性。培养外周血单核细胞(PBMC)和克氏锥虫(T. cruzi trypmasastigotes)进行细胞毒性和抗寄生虫活性分析。在0.1 M TRIS-HCl缓冲液(pH 7.2)中机械搅拌获得粗提物,并通过DEAE-Sephadex A-50层析和FPLC纯化蛋白质,用不同浓度粗提物处理PBMC,评估细胞毒性。用纯化蛋白和苯并硝唑处理后,通过测量细胞因子(IFN-γ、TNF、IL-2、IL-6和IL-10)来分析感染和未感染PBMC的免疫应答。体外实验表明,粗提物和纯化后的15 kDa蛋白对锥乳线虫均呈剂量依赖性毒性,分别在1000和200 μg/mL浓度下杀灭80%以上的锥乳线虫。提取物和蛋白对PBMC均无毒性,蛋白(SI: 20.7)比苯并硝唑(SI: 11.5)具有更强的选择性。结果表明,纯化蛋白可调节克氏锥虫感染个体的免疫反应,诱导保护性Th1反应,同时通过适当的IL-10水平控制过度的炎症反应。anti-T。这种蛋白的克氏活性,单独使用或与商业药物联合使用,表明它可能是一种低成本、更安全、更耐受的恰加斯病治疗方法。
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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
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.
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