Antitumor and immunomodulatory activity of fucoidan from the brown alga Lessonia trabeculata (Lessoniaceae) on breast cancer spheroids / Actividad antitumoral e inmunomoduladora de fucoidan del alga parda Lessonia trabeculata (Lessoniaceae) en esferoides de cáncer de mama

Abstract Introduction: The therapeutic benefits of the brown algae fucoidan in the treatment of breast cancer have attracted considerable interest in recent years. However, research using spheroids which provide relevant results in trials for antitumor and immunomodulatory products because they adequately simulate the tumor microenvironment, is limited. Objective: To evaluate the antitumor and immunomodulatory activity of Lessonia trabeculata fucoidan (LtF), native to the Peruvian Sea, on two types of multicellular tumor spheroids. Methods: The study was conducted from January to December 2021. Two types of spheroides were elaborated: from 4T1 tumor cells (MTS), and from 4T1 tumor cells+mouse splenocytes (MTSs). The antitumor activity of LtF was evaluated in MTS by quantifying cell viability with MTT. Immunomodulatory activity was determined in MTSs using the IC50 for two types of treatment: simple, fucoidan alone (LtF) and combined, fucoidan+doxorubicin (LtF+Dox). Pro-inflammatory (TNF-α, IL-6) and anti-inflammatory (IL-10, TGF-β) cytokine production was quantified by sandwich ELISA 72 h after treatment. Dox was used as positive control in all assays. Results: LtF exerted antitumor activity as evidenced by increased necrotic zone and cell debris formation compared to the untreated control. Antitumor activity was concentration dependent between 100 and 6 000 μg/ml. In MTSs, simple treatment increased IL-6 and decreased IL-10 and TGF-β production. The combined treatment significantly reduced TGF-β production. In both treatments and Dox, there was an increase in IL-6 compared to the untreated control. The highest production of IL-10 and TGF-β was observed in the untreated control, compatible with a highly immunosuppressive tumor microenvironment. Conclusions: LtF is a good candidate for the treatment of breast cancer and can immunomodulate the tumor microenvironment alone or in combination with Dox.

Resumen Introduccción: Los beneficios terapéuticos del fucoidan de algas pardas en el tratamiento del cáncer de mama han despertado gran interés en los últimos años. Sin embargo, las investigaciones con esferoides son limitadas, éstos proporcionan resultados relevantes en ensayos de productos antitumorales e inmunomoduladores porque simulan adecuadamente el microambiente tumoral. Objetivo: Evaluar la actividad antitumoral e inmunomoduladora del fucoidan de Lessonia trabeculata (LtF), nativa del Mar Peruano, en dos tipos de esferoides tumorales multicelulares. Métodos: El estudio se realizó de enero a diciembre de 2021. Se elaboraron dos tipos de esferoides: con células tumorales 4T1 (MTS) y con células tumorales 4T1+esplenocitos de ratón (MTSs). La actividad antitumoral de LtF se evaluó en MTS cuantificando la viabilidad celular con MTT. La inmunomodulación se determinó en MTSs utilizando la IC50 para dos tipos de tratamiento: simple, fucoidan solo (LtF) y combinado, fucoidan+doxorubicina (LtF+Dox). La producción de citoquinas proinflamatorias (TNF-α, IL-6) y antiinflamatorias (IL-10, TGF-β) se cuantificó mediante ELISA sándwich 72 h post-tratamiento. En todos los ensayos se utilizó Dox como control positivo. Resultados: En los MTS, el LtF ejerció actividad antitumoral evidenciada por aumento de la zona necrótica y formación de restos celulares respecto al control no tratado. La actividad antitumoral fue concentración-dependiente entre 100 y 6 000 μg/ml. En los MTSs, con el tratamiento simple se incrementó IL-6 y disminuyeron IL-10 y TGF-β. El tratamiento combinado redujo significativamente la producción de TGF-β. Los dos tratamientos y Dox incrementaron IL-6 respecto al control no tratado. La mayor producción de IL-10 y TGF-β se observó en los no tratados, compatible con un microambiente tumoral altamente inmunosupresor. Conclusiones: El LtF es un buen candidato para tratar el cáncer de mama y puede inmunomodular el microambiente tumoral solo o en combinación con Dox.

Plantas utilizadas en la medicina popular paraguaya como antiinflamatorias / Plants used as anti-inflammatory in Paraguayan folk medicine

In this contribution, we present 37 species and a variety of medicinal plants used as anti-inflammatory, corresponding to 27 families (1 Pteridophyta, one monocot, 25 dicot), according to the source, 25 species are native, 9 exotic and 2 are acclimated. Regular visits to the central markets of Asuncion (Municipal Market No. 4), San Lorenzo and Luque, Central Department; Paraguarí, Paraguarí Department and Caacupé, Department of Cordillera were made. The highest percentage of the species reported as anti-inflammatory, corresponds to the San Lorenzo market (70 percent). Only 11percent of the species listed in this work as anti-inflammatory or anti-inflammatory for any condition have been reported as such in all markets, while the highest percentage (32 percent) have been reported as anti-inflammatory in one market only. Medicinal plant sellers were interviewed about plants used as anti-inflammatory, data were taken, reference material was acquired, samples of pecies were identified and entered the collection of medicinal plants of the FCQ Herbarium. Thus, they provide an update on anti-inflammatory medicinal plants, used in Paraguay.

En esta contribución se presentan 37 especies y una variedad de plantas medicinales utilizadas como antiinflamatorias, que corresponden a 27 familias (1 de pteridófita, 1 monocotiledónea, 25 dicotiledóneas); según el origen, 25 especies son nativas, 9 son exóticas y 2 aclimatadas. Se realizaron visitas periódicas a los mercados centrales de Asunción (Mercado Municipal Nº 4); San Lorenzo y Luque, Departamento Central; Paraguarí, Departamento de Paraguarí y Caacupé, Departamento de Cordillera. El mayor porcentaje de las especies reportadas como antiinflamatorias, corresponde al mercado de San Lorenzo (70 por ciento). Solo el 11 por ciento de las especies citadas en este trabajo como antiinflamatorias o para alguna afección antiinflamatoria, se han reportado como tal en todos los mercados; mientras que el mayor porcentaje (32 por ciento), se han reportado como antiinflamatorias sólo en un mercado. Se entrevistaron a los vendedores de plantas medicinales acerca de las plantas que se emplean como antiinflamatorias, se tomaron los datos, se adquirió material de referencia de las especies, se identificaron las muestras y se ingresaron a la colección de plantas medicinales del Herbario FCQ. De esta manera, se aportan datos actualizados sobre plantas medicinales antiinflamatorias, utilizadas en Paraguay.

Análise do envolvimento de células T reguladoras na hanseníase / Analysis of the involvement of regulatory T cells in leprosy

A hanseníase é uma doença crônica causada por Mycobacterium leprae e apresenta diversas formas clínicas. O entendimento da interação parasita-hospedeiro na hanseníase evidenciou que ocorre a persistência assintomática do patógeno, caracterizando um estado de latência. Os fatores mais importantes relacionados com a permanência do patógeno são: a patogenicidade do agente infeccioso e o perfil da resposta imune, no qual os eventos de migração celular, produção de citocinas, as células efetoras e reguladoras são extremamente relevantes. As células T reguladoras (Treg) desempenham papel central na regulação da resposta imune em infecções crônicas o que favorece a persistência do patógeno. A importância de células T reguladores na hanseníase ainda é pouco conhecida. Neste trabalho investigou-se a presença de células T reguladoras em lesões e sangue periférico de indivíduos com hanseníase. Inicialmente avaliou-se a proliferação e a produção de citocinas por células mononucleares do sangue periférico (PBMC) de pacientes com hanseníase. Os resultados evidenciaram que não há diferenças quanto à proliferação de células T e produção de IFN-γ e TNF-α por células desses pacientes, mas a produção de IL-4 e IL-5 foi detectada apenas entre os pacientes com hanseníase virchoviana. Em relação à presença de células T reguladoras, os resultados evidenciaram aumento no número de linfócitos T CD4+CD25+FoxP3+ no sangue periférico de pacientes com hanseníase virchoviana. As células T reguladoras dos pacientes com hanseníase apresentaram elevada expressão de moléculas co-inibitórias PD-1, CTLA-4, GITR e ICOS. De modo relevante, as células T CD4+CD25+ isolados de pacientes com hanseníase virchoviana apresentaram maior atividade supressora quando comparado às células isoladas de pacientes com hanseníase tuberculóide. As células T CD4+CD25+ de pacientes com hanseníase virchoviana inibiram a proliferação de PBMC alogênico e a produção de IFN-γ e TNF-α...

Leprosy is caused by Mycobacterium leprae and its clinical features depend on the host immune background. The understanding of parasite-host interactions in leprosy have highlighted asymptomatic persistence of the pathogen, which indicates that this infection becomes latent. The most important factors related to the permanence of pathogens are: the pathogenicity of the infectious agents; the profile of the immune response developed by the host whose events of cellular migration, cytokines production, and the effector and regulatory cells are extremely relevant. The regulatory T cells (Treg) seem to play a central role in the regulation of the immune response in chronic infections, which favors the persistence of the pathogen. Herein, we analyzed the relation between tuberculoid and lepromatous leprosy with the presence and function of T regulatory cells from peripheral blood mononuclear cells (PBMC) and skin lesions from these patients. First, the proliferation and cytokine production of PBMC isolated from leprosy patients were analyzed. We did not observe any difference in the proliferation ability or IFN-γ and TNF-α release; however, the production of IL-4 and IL-5 was detected only in patients with lepromatous leprosy. Furthermore, T CD4+CD25+FoxP3+ cells were detected in the PBMC of patients with leprosy and these cells from lepromatous patients showed high expression of co-inhibitory molecules such as PD-1, GITR, CTLA-4 and ICOS. T CD4+CD25+cells isolated from patients with lepromatous leprosy were significantly more suppressive than the cells obtained from tuberculoid patients. In addition, TCD4+CD25+ cells isolated from patients with lepromatous leprosy inhibited allogeneic PBMC proliferation and their production of IFN-γ and TNF-α. The results also demonstrated that IL- 10 and TGF-ß were co-expressed with CD25+ cells at the inflammatory infiltrate of skin lesions from lepromatous patients, but similar results were not detected among tuberculoid...

ácidos grasos omega-3 (epa y dha) y su aplicación en diversas situaciones clínicas / Omega-3 fatty aciids (epa and dha) and its application in diverse clinical situations

Omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) eicosapentaenoic acid (EPA) and docosahexae-noic acid (DHA) are found in significant amounts in fatty fish (tuna fish, mackerel and salmon) and especially in the oil obtained from these species, which is actually utilized as a nutritional supplement (nutraceutical). After ingestion, both EPA and DHA are rapidly incorporated into cellular membrane phospholipids where they can be released by lipooxygenases and cyclooxygenases enzymes and transformed in powerful bioactive products wich have cytoprotective and especially anti-inflammatory activities. Clinical and epidemiological evidence have firmly established that consumption ofEPA and DHA may contribute to the prevention and / or treatment of a number of diseases, especially those where inflammation plays a remarkable role in its development. EPA and DHA exhibit potent anti-inflammatory properties, either via the generation of anti-inflammatory products, such as the resol-vins, or by blocking inflammatory agents. In the present paper we review possible clinical applications of EPA and DHA in pathologies, such as cardiovascular and neurodegenerative diseases, cancer, inflammatory bowel disease, rheumatoid arthritis and ischemia - reperfusion injury. The evidence suggests that ω-3 LCPUFA may have promising applications in the prevention and / or treatment of different clinical and nutritional pathologies.

Los ácidos grasos poliinsaturados de cadena larga omega-3 (AGPICL ω-3) como el ácido eicosapentaenoico (EPA) y docosahexaenoico (DHA) se encuentran en cantidades importantes en los pescados grasos (atún, jurel y salmón) y especialmente en el aceite obtenido de estas especies, el cual actualmente se utiliza como suplemento nutricional (nutracéutico). Tanto el EPA como el DHA, luego de ser ingeridos, se incorporan rápidamente a los fosfolípidos de las membranas celulares donde pueden ser liberados por enzimas lipooxigenasas y ciclooxigenasas, originando productos con potentes propiedades citoprotectoras y especialmente antiinflamatorias. La evidencia clínica y epidemiológica de múltiples estudios permite establecer que el consumo de EPA y DHA puede contribuir a la prevención y/o tratamiento de una serie de patologías, especialmente aquellas donde la inflamación juega un papel preponderante en su desarrollo. El EPA y el DHA presentan propiedades antiinflamatorias, vía la generación ya sea de agentes anti-inflamatorios, como las resolvinas, o a través del bloqueo de agentes pro-inflamatorios. En el presente artículo se presentan evidencias sobre las posibles aplicaciones clínicas de los AGPICL ω-3 en patologías tales como las enfermedades cardiovasculares, neurodegenerativas, cáncer, enfermedad inflamatoria intestinal, artritis reumatoidea e injuria por isquemia - reperfusión. La evidencia sugiere que los AGPICL ω-3 pueden tener promisorias aplicaciones en el tratamiento y/o la prevención de diferentes patologías clínicas o nutricionales.

Levantamento etnobotânico de plantas popularmente utilizadas como antiúlceras e antiinflamatórias pela comunidade de Pirizal, Nossa Senhora do Livramento-MT, Brasil / Ethnobotanical survey of plants popularly used as anti-ulcer and anti-inflammatory in Pirizal, Nossa Senhora do Livramento-MT, Brazil

O trabalho teve por objetivo proceder o levantamento etnobotânico das espécies vegetais utilizadas popularmente no Distrito de Pirizal - MT, no pantanal mato-grossense, como antiúlceras e antiinflamatórias. A entrevista aberta foi realizada através da aplicação de um roteiro base a 38 informantes adultos, na faixa etária de 25 a 75 anos. Indagou-se o nome popular das plantas, partes utilizadas, preparados e vias de administração, e realizou-se a revisão bibliográfica das plantas mais citadas no estudo, utilizando-se as bases de dados convencionais. Foram citadas 49 espécies pertencentes a 47 gêneros e 32 famílias, destacando-se a família Fabaceae. As plantas mais citadas simultaneamente como antiúlceras e antiinflamatórias foram Lafoensia pacari St. Hil. (9,2 por cento), Hyptis crenata Pohl (8,8 por cento), Hyptis suaveolens (L.) Poit (6,7 por cento), Stachytarpheta cayenensis (L.C.Rich) Vahl (5,8 por cento), Waltheria indica L. (5 por cento), Strychnos pseudoquina St. Hil. (4,2 por cento) e Vatairea macrocarpa (Benth.) Ducke (3,3 por cento). A parte da planta mais citada foi a folha (57,1 por cento), a via de administração mais utilizada no tratamento das úlceras gástricas foi a oral (100 por cento), com preferência para os chás (75 por cento), enquanto nas inflamações foram os banhos tópicos (60 por cento.). A revisão bibliográfica apontou a necessidade de aprofundar os estudos químico-farmacológicos para Vatairea macrocarpa (Benth.) Ducke e Hyptis crenata Pohl.

An ethnobotanical survey was conduced to study the vegetal species from Pantanal, in the district of Pirizal-MT, popularly used as anti-inflammatory and anti-ulcer. Ethnobotanical data were collected through open interviews and ethnopharmacology questionnaire with 38 local informers, in the age group of 25 to 75 years old. The local name, the part normally used, the mode of preparation and the administration route were asked to them. A bibliographic review of the plants most cited in the study was carried out using the conventional databases. A total of 49 species were cited belonging to 47 genera and 32 families, with emphasizing the Fabaceae family. The plants most cited were Lafoensia pacari St. Hil (9.2 percent), Hyptis crenata Pohl (8.8 percent), Hyptis suaveolens (L.) Poit (6.7 percent), Stachytarpheta cayenensis (L.C.Rich) Vahl (5.8 percent), Waltheria indica L. (5 percent), Strychnos pseudoquina St.Hil (4.2 percent) and Vatairea macrocarpa (Benth.) Ducke (3.3 percent). The part of the plant most cited was the leaf (57.1 percent), the most used administration route in the treatment of ulcers was oral (100 percent), in the form of teas (75 percent), while in the inflammations, topical baths were preferentially used (60 percent). The literature review indicated the need for further chemical-pharmacological studies on Vatairea macrocarpa (Benth.) Ducke and Hyptis crenata Pohl.