Avaliação dos perfis fitoquímicos, antioxidante e citotóxicos do extrato alcoólico de folhas de cajá-manga (spondias dulcis) / Evaluation of phytochemical, antioxidant and cytotoxic profiles of the alcoholic extract of cajamanga leaves (spondias dulcis) / Evaluación de perfiles fitoquímicos, antioxidante y citotóxicos del extracto alcohólico de hojas de cajamanga (spondias dulcis)

Introdução: As espécies de plantas frutíferas, além da importância nutricional, podem ser usadas como fontes de compostos bioativos de interesse para o desenvolvimento de novos medicamentos. Entre as plantas com potencial terapêutico destacamos a Spondias dulcis (cajá-manga) indicada pela medicina tradicional para tratamento de condições médicas dos sistemas tegumentar, respiratório e genitourinário. Objetivos: Realizar a caraterização fitoquímica, antioxidante e citotóxica do extrato alcoólico bruto de folhas de Spondia dulcis. Material e Métodos: O extrato bruto foi obtido por percolação com o uso de 20 g das folhas secas e trituradas de Spondia dulcis e 100 ml de etanol a 70o por 24h. Na padronização do extrato foram utilizadas diferentes reações para análises de identificação de compostos do metabolismo secundário, bem como a determinação da atividade antioxidante pela captura do radical livre do DPPH. Após retirada do álcool por rotaevaporação, foram realizados testes de citotoxidade in vitro (hemólise) em solução glicosilada (5%) de hemácias (4%) nas diferentes concentrações do extrato (0,5%, 1% e 1,5%). Resultados: As análises fitoquímicas qualitativas identificaram a presença de compostos fenólicos, flavonoides, taninos genéricos e cumarinas. A avaliação dos compostos terpenoides mostrou presença de saponinas e ausência de sesquiterpenos e triterpenos. Os alcaloides foram detectados pelas reações de Bouchardat, Dragendorff, Mayer e Sheibler. A análise da atividade antioxidante do extrato indicou alta capacidade antioxidante (71%). No ensaio de hemólise a citotoxidade foi baixa nas concentrações de 0,5% e 1% e relativa na concentração de 1,5%. Conclusão: O extrato alcoólico bruto de Spondia dulciscontém compostos bioativos anti-inflamatórios, alta capacidade antioxidante e baixa citotoxicidade até a concentração de 1,5% com potencial de aplicação farmacológica (AU)

Introduction: Fruit plant species, in addition to their nutritional importance, can be used as sources of bioactive compounds of interest for the development of new drugs. Among the plants with therapeutic potential, we highlight Spondias dulcis (cajá-manga) indicated by traditional medicine for the treatment of medical conditions of the integumentary, respiratory and genitourinary systems. Objectives: To carry out the phytochemical, antioxidant and cytotoxic characterization of the leaves crude alcoholic extract of Spondia dulcis. Material and Methods: The crude extract was obtained by percolation using 20 g of dried and crushed leaves of Spondia dulcis and 100 ml of ethanol at 70° for 24 hours. In the standardization of the extract, different reactions were used to analyze the identification of compounds of secondary metabolism, as well as the determination of the antioxidant activity by capturing the free radical of DPPH. After removing the alcohol by rotary evaporation, in vitro cytotoxicity tests (hemolysis) were performed in a glycosylated solution (5%) of red blood cells (4%) at different concentrations of the extract (0.5%, 1% and 1.5%). Results: Qualitative phytochemical analyzes identified the presence of phenolic compounds, flavonoids, generic tannins and coumarins. The evaluation of terpenoid compounds showed the presence of saponins and the absence of sesquiterpenes and triterpenes. Alkaloids were detected by Bouchardat, Dragendorff, Mayer and Sheibler reactions. The analysis of the antioxidant activity of the extract indicated that the crude extract of Spondia dulcis has a high antioxidant capacity (71%). In the hemolysis assay, cytotoxicity was low at concentrations of 0.5% and 1% and relative at concentrations of 1.5%. Conclusion: The crude alcoholic extract of Spondia dulcis contains anti-inflammatory bioactive compounds, high antioxidant capacity and low cytotoxicity up to a concentration of 1.5% with potentialfor pharmacological application (AU)

Introducción: Las especies de plantas frutales, además de su importancia nutricional, pueden ser utilizadas como fuentes de compuestos bioactivos de interés para el desarrollo de nuevos fármacos. Entre las plantas con potencial terapéutico destacamos Spondias dulcis (cajamanga) indicada por la medicina tradicional para el tratamiento de afecciones médicas de los sistemas tegumentario, respiratorio y genitourinario. Objetivos: Realizar la caracterización fitoquímica, antioxidante y citotóxica del extracto alcohólico crudo de hojas de Spondia dulcis. Material y Métodos: El extracto crudo se obtuvo por percolación utilizando 20 g de hojas secas y trituradas de Spondia dulcis y 100 ml de etanol a 70° durante 24 horas. En la estandarización del extracto se utilizaron diferentes reacciones para analizar la identificación de compuestos de metabolismo secundario, así como la determinación de la actividad antioxidante mediante la captura del radical libre de DPPH. Después de eliminar el alcohol por evaporación rotatoria, se realizaron pruebas de citotoxicidad (hemólisis) in vitro en una solución glicosilada (5%) de glóbulos rojos (4%) a diferentes concentraciones del extracto (0,5%, 1% y 1,5%). Resultados: Los análisis fitoquímicos cualitativos identificaron la presencia de compuestos fenólicos, flavonoides, taninos genéricos y cumarinas. La evaluación de los compuestos terpenoides mostró la presencia de saponinas y la ausencia de sesquiterpenos y triterpenos. Los alcaloides fueron detectados por las reacciones de Bouchardat, Dragendorff, Mayer y Sheibler. Los estudios han demostrado que el extracto crudo de Spondiadulcis tiene una alta capacidad antioxidante (71%). En el ensayo de hemólisis, la citotoxicidad fue baja a concentraciones de 0,5% y 1% y relativa a concentraciones de 1,5%. Conclusión: El extracto alcohólico crudo de Spondia dulcis contiene compuestos bioactivos antiinflamatorios, alta capacidad antioxidante y baja citotoxicidad hasta una concentración de 1,5% conpotencial de aplicación farmacológica (AU)

Estudo comparativo dos perfis fitoquímicos e citotóxicos do extrato alcoólico de folhas de graviola (annona muricata) e fruta do conde (annona squamosa) / Comparative study of the phytochemical and cytotoxic profiles of the alcoholic extract of soursop (annona muricata) and custard apple (annona squamosa) leaves / Estudio comparativo de los perfiles fitoquímicos y citotóxicos del extracto alcohólico de hojas de guanábana (annona muricata) y del conde (annona squamosa)

Introdução: As plantas apresentam potencial medicinal devido aos metabólitos secundários e possuem compostos com alto potencial anti-inflamatório, com possibilidades terapêuticas. Das espécies vegetais de interesse destacamos e comparamos a graviola (Annona muricata) e a fruta do conde (Annona squamosa). Objetivo: Comparar o potencial do extrato alcoólico bruto de folhas da graviola e fruta do conde em ensaios fitoquímicos e citotóxicos. Método: Os extratos de folhas de graviola e fruta do conde foram obtidos por percolação, com o uso de 20g de folhas secas e trituradas com 100 ml de álcool de cereais. Na padronização dos extratos foram utilizadas análises de idenficação de componentes químicos, os taninos, flavonoides, saponinas e alcaloides, por meio de difrentes reações químicas e os antioxidantes foram analisados pela atividade do DPPH. A citotoxicidade das diferentes concentrações dos extratos também foram analisadas por hemólise e pelo teste da membrana corioalantide (CAM). Resultados: As análises fitoquímicas indicaram a presença de alcaloides, taninos, flavonoides e saponinas para ambos os extratos com alta capacidade antioxidante. Os testes de hemólise e CAM mostraram ausência de citotoxicidade na concentração de 2% e 4% para ambos os extratos e elevada citotoxicidade em 10% para o extrato de graviola. Conclusão: O extrato alcoólico das folhas da graviola e fruta do conde mostraram importante perfil antioxidante e com compostos anti-inflamatórios com pouca diferença entre os extratos o que estimula estudos futuros e continuidade para exploração anti-inflamatória.

Introduction: Plants have medicinal potential due to secondary metabolites and have compounds with high antiinflammatory potential, with therapeutic possibilities. Of the plant species of interest we highlight and compare the graviola (Annona Muricata) and the fruit of the count (Annona squamosa). Objective: To compare the potential of crude alcoholic extract of soursop and conde fruit leaves in phytochemical and cytotoxic assays. Method: The leaves extracts of soursop and fruit of the count were obtained by percolation, with the use of 20g of dry leaves and crushed with 100 ml of grain alcohol. In the standardization of the extracts were used idenfication analyzes of chemical components, tannins, flavonoids, saponins and alkaloids, through different chemical reactions and antioxidants were analyzed by the activity of DPPH. The cytotoxicity of the different concentrations of the extracts were also analyzed by hemolysis and by the corioalantide membrane test (CAM). Results: Phytochemical analysis indicated the presence of alkaloids, tannins, flavonoids and saponins for both extracts with high antioxidant capacity. The hemolysis and CAM tests showed absence of cytotoxicity at the concentration of 2% and 4% for both extracts and high cytotoxicity in 10% for graviola extract. Conclusion: The alcoholic extract of the leaves of soursop and fruit of the count showed important antioxidant profile and with anti-inflammatory compounds with little difference between the extracts which stimulates future studies and continuity for anti-inflammatory exploration.

Introducción: Las plantas tienen potencial medicinal debido a los metabolitos secundarios y poseen compuestos con alto potencial antiinflamatorio, además de ser utilizadas en tratamientos terapéuticos. De las especies vegetales de interés, destacamos y comparamos la guanábana (Annona muricata) y la fruta del conde (Annona squamosa). Objetivo: Comparar el potencial del extracto alcohólico crudo de hojas de guanábana y chirimoya en ensayos fitoquímicos y citotóxicos. Método: El extracto de hojas de guanábana y fruta del conde se obtuvo por percolación, utilizando 20g de hojas secas y trituradas con 100 ml de alcohol de grano. En la estandarización de los extractos se utilizaron análisis para identificar componentes químicos, taninos, flavonoides, saponinas y alcaloides, a través de diferentes reacciones químicas y los antioxidantes fueron analizados por la actividad de DPPH. También se analizó la citotoxicidad de diferentes concentraciones de extractos por hemólisis y por la prueba de membrana de corioalantida (CAM). Resultados: Los análisis fitoquímicos indicaron la presencia de alcaloides, taninos y flavonoides y saponinas para ambos extractos con alta capacidad antioxidante. Las pruebas de hemólisis y CAM mostraron ausencia de citotoxicidad a una concentración del 4% y alta citotoxicidad a partir del 10% también para ambos extractos. Conclusión: El extracto alcohólico de hojas de guanábana y chirimoya mostró importantes perfiles antioxidantes y con compuestos antiinflamatorios, lo que estimula futuros estudios y continuidad para la exploración antiinflamatoria.

Evaluation of the healing properties of Garcinia brasiliensis extracts in a cutaneous wound model.

ETHNOPHARMACOLOGICAL RELEVANCE: Wound healing is a complex process that can leave pathological scars, especially in case of infections from opportunistic microorganisms. In this context, herbal medicines open up great possibilities for investigation. One of the species of interest native to Brazil is Garcinia brasiliensis ("bacupari"). Traditionally known for treating wounds and ulcers, G. brasiliensis presents anti-inflammatory, antioxidant and antimicrobials properties. But, its wound healing profile in experimental models, in order to validate its efficacy, is still litle studied. AIM OF THE STUDY: Thus, the objective of this work was to evaluate, in an infected cutanous wound model, the potential of formulations incorporated with G. brasiliensis leaves extracts. MATERIALS AND METHODS: Crude extract (CE), Ethyl Acetate Fraction (EAF) and Hexanic Fraction (HF) were submitted to phytochemical assays, high performance thin layer chromatography (HTPLC) and cytotoxicity studies. CE and EAF were also tested for microbicidal properties and incorporated in cream and gel formulations at 10% concentration. After stability testing, the gel formulations with CE or EAF at 10% were selected and applied to skin wounds infected or not with Staphylococcus aureus in Wistar rats. The healing potenttial of the extracts was verified by the expression of the protein Annexin A1 (AnxA1), related to the processes of inflammation and antifibrotic function, the cells immunostaining for Gasdermin-D (GSDM-D), a marker of pyroptotic cell death, and the dosage of interleukin-10 (IL-10) and monocyte chemotactic protein (MCP)-1 inflammatory mediators. RESULTS: Phytochemical studies indicated the presence of compounds of pharmacological interest, including Catechin, Quercetin and Berberine in addition to low cytotoxicity of CE and EAF at 10%. After the 6-day topical treatments, CE and EAF gel formulations demonstrated to control the pruritus formation process. The treatments decreased AnxA1 expression and the amount of cells immunostained for GSDM-D, and increased the expression of MCP-1 in infected wounds. CONCLUSIONS: Together, the results show important anti-inflammatory profile and skin healing potential of CE and EAF from G. brasiliensis leaves, even in infected lesions, with therapeutic perspectives.

Administração do extrato de garcinia brasiliensis e modulação do ambiente tumoral em modelo de carcinogênese pulmonar / Administration of garcinia brasiliensis extract and modulation of the tumor environment in a model of pulmonary carcinogenesis / Administración de extracto de garcinia brasiliensis y modulación del ambiente tumoral en un modelo de carcinogénesis pulmonar

Introdução: O benzopireno é um dos principais hidrocarbonetos aromáticos policíclicos presentes no ambiente e com alta capacidade carcinogênica, sendo, portanto, usado em modelos in vivo de carcinogênese pulmonar. Investigações têm mostrado o envolvimento dos mastócitos na modulação do ambiente tumoral e que os fármacos anti-inflamatórios podem reduzir a incidência de câncer de pulmão. Entre as possibilidades terapêuticas estão os fitoterápicos. O extrato de Garcinia brasiliensis, conhecido popularmente como bacupari, mostra propriedades anti-inflamatórias e antitumorais, mas ainda pouco estudado em modelos animais. Objetivos: Avaliar os efeitos da administração do extrato alcoólico de G. brasiliensis em modelo de carcinogênese induzida por benzopireno. Material e Método: O extrato bruto foi obtido por percolação com o uso de 20 g das folhas secas e trituradas de G. brasiliensis e 100 ml de etanol a 70%, por 24h. Ratos Wistar foram divididos em 3 grupos, um controle sem indução ou tratamento, um induzido pelo benzopireno (100 mg/kg, diluído em DMSO e administrado intraperitonealmente, uma única aplicação) e um grupo tratado por gavagem (1 ml) com extrato de bacupari a 4% (3x/semana, por 7 semanas, a partir da 15o semana da indução. Os animais de todos os grupos foram eutanasiados após 21 semanas para coleta dos pulmões que foram processados para análises histopatológicas (HE) e histoquímicas (Azul de Toluidina e Azul de Alcian Safranina) para quantificação dos mastócitos. Resultados: Os resultados das análises histopatológicas mostraram desorganização do parênquima pulmonar, aumento de tecido linfático associado aos brônquios, grande influxo de células inflamatórias e regiões de displasia. Pela coloração de azul de toluidina os mastócitos foram identificados na forma intacta e desgranulada (em processo de ativação). Na coloração conjunta Azul de Alcian e Safranina, os mastócitos corados em azul representam as fases iniciais do processo de maturação, enquanto os corados em vermelho estão maduros. A quantificações evidenciaram maior quantidade de mastócitos desgranulados, azul de Alcian e mistos (corados pelo Azul de Alcian e Safranina) nos grupos tratados com o extrato. Conclusão: Os dados indicam que o ambiente tumoral nos animais tratados mostra maior modulação dos mastócitos, com mais células jovens e ativadas. Mais análises serão realizadas para verificar se a ativação dos mastócitos promovida pelo tratamento com o extrato ocorre para contenção ou promoção do processo tumoral.(AU)

Introduction: Benzopyrene is one of the main polycyclic aromatic hydrocarbons present in the environment and with a high carcinogenic capacity, being, therefore, used in in vivo models of lung carcinogenesis. Investigations have shown the involvement of mast cells in modulating the tumor environment and that anti-inflammatory drugs can reduce the incidence of lung cancer. Among the therapeutic possibilities are herbal medicines. Garcinia brasiliensis extract, popularly known as bacupari, shows anti-inflammatory and antitumor properties, but still little studied in animal models. Objectives: To evaluate the effects of the administration of the alcoholic extract of G. brasiliensis in a model of carcinogenesis induced by benzopyrene. Material and Methods: The crude extract was obtained by percolation using 20 g of dried and crushed leaves of G. brasiliensis and 100 ml of 70% ethanol for 24 hours. Wistar rats were divided into 3 groups, a control without induction or treatment, one induced by benzopyrene (100 mg/kg, diluted in DMSO and administered intraperitoneally, a single application) and a group treated by gavage (1 ml) with bacupari extract. at 4%...(AU)

Introducción: El benzopireno es uno de los principales hidrocarburos aromáticos policíclicos presentes en el ambiente y tiene una elevada capacidad carcinogénica, por lo que se utiliza en modelos in vivo de carcinogénesis pulmonar. Las investigaciones han demostrado la implicación de los mastocitos en la modulación del entorno tumoral y que los fármacos antiinflamatorios pueden reducir la incidencia del cáncer de pulmón. Entre las posibilidades terapéuticas están las fitoterapias. El extracto de Garcinia brasiliensis, conocido popularmente como bacupari, muestra propiedades antiinflamatorias y antitumorales, pero todavía está sido poco estudiado en modelos animales. Objetivos: Evaluar los efectos de la administración del extracto alcohólico de G. brasiliensis en el modelo de carcinogénesis inducido por el benzopireno. Material y métodos: El extracto crudo se obtuvo por percolación utilizando 20 g de hojas de G. brasiliensis secas y trituradas y 100 ml de etanol al 70%, durante 24h. Las ratas Wistar fueran divididas en 3 grupos, uno de control sin inducción ni tratamiento, otro inducido por benzopireno (100 mg/kg, diluido en DMSO y administrado por vía intraperitoneal, una sola aplicación) y un grupo tratado por gavage (1ml) con extracto de bacupari 4% (3x/semana, durante 7 semanas, desde la 15ª semana de inducción). Los animales de todos los grupos fueron eutanasiados después de 21 semanas para recoger los pulmones que se procesaron para los análisis histopatológicos (HE) e histoquímicos (azul de toluidina y azul de safranina) para la cuantificación de los mastocitos. Resultados: Los resultados de los análisis histopatológicos mostraron desorganización del parénquima pulmonar, aumento del tejido linfoide asociado a los bronquios, gran afluencia de células inflamatorias y regiones de displasia. Mediante la tinción con azul de toluidina, los mastocitos se identificaron como intactos y degranulados (en proceso de activación). En la tinción conjunta de azul Alcian y Safranina, los mastocitos teñidos de azul representan las fases iniciales del proceso de maduración, mientras que los teñidos de rojo son maduros. La cuantificación mostró una mayor cantidad de mastocitos degranulados, azul Alcian y mixtos (teñidos con azul Alcian-Safranin) en los grupos tratados con el extracto. Conclusión: Los datos indican que el entorno del tumor en los animales tratados muestra una mayor modulación de los mastocitos, con más células jóvenes y activadas. Se llevarán a cabo más análisis para verificar si la activación de los mastocitos promovida por el tratamiento con el extracto se produce para contener o promover el proceso tumoral.(AU)

Protective effects of piperlongumin in the prevention of inflammatory damage caused by pulmonary exposure to benzopyrene carcinogen.

Benzopyrene is one of the main polycyclic aromatic hydrocarbons with carcinogenic capacity. Research has shown that anti-inflammatory drugs can reduce the incidence of lung cancer. In this scenario, we highlight piperlongumin (PL), an alkaloid from Piper longum with anti-inflammatory properties. Therefore, our aim was to study the effect of PL administration in a model of pulmonary carcinogenesis induced by benzopyrene in Balb/c mice. Animals were divided into 3 groups (n = 10/group): sham (10% DMSO), induced by benzopyrene (100 mg/kg, diluted in DMSO) without treatment (BaP) for 12 weeks and induced by benzopyrene and treated with PL (BaP/PL) (2 mg/kg in 10% DMSO) from the eighth week post-induction. Animals were weighed daily and pletsmography was performed in the 12th week. Genotoxicity and hemoglobin levels were analyzed in blood and quantification of leukocytes in bronchoalveolar lavage (BAL). Lungs were collected for histopathological evaluation, immunohistochemical studies of annexin A1 (AnxA1), cyclooxygenase 2 (COX-2), anti-apoptotic protein Bcl-2 and nuclear transcription factor (NF-kB) and also the measurement of interleukin cytokines (IL)-1ß, IL-17 and tumor necrosis factor (TNF) -α. Treatment with PL reduced the pulmonary parameters (p < 0,001) of frequency, volume and pulmonary ventilation, decreased lymphocytes, monocytes and neutrophils in BAL (p < 0,05) as well as blood hemoglobin levels (p < 0,01). PL administration also reduced DNA damage and preserved the pulmonary architecture compared to the BaP group. Moreover, the anti-inflammatory effect of PL was evidenced by the maintenance of AnxA1 levels, reduction of COX-2 (p < 0,05), Bcl-2 (p < 0,01) and NF-kB (p < 0,001) expressions and decreased IL-1ß, IL-17 (p < 0,01) and TNF-α (p < 0,05) levels. The results show the therapeutic potential of PL in the treatment of pulmonary anti-inflammatory and anti-tumor diseases with promising therapeutic implications.

Perfis fitoquímicos, microbiológicos, citotóxicos e antiinflamatórios do extrato alcoólico de folhas de atemoia (annona squamosa, l. X annona cherimola) / Phytochemical, microbiological, cytotoxic and anti-inflammatory profiles of the alcoholic extract of atemoy leaves (annona squamosa, l. X annona cheremola) / Perfiles fitoquímico, microbiológico, citotóxico y antiinflamatorio del extracto alcohólico de hojas de atemoy (annona squamosa, l. X annona cheremola)

Introdução: Os extratos alcoólicos de plantas com potencial medicinal possuem compostos com alto potencial antiinflamatório e aplicação terapêutica. Dentre as espécies vegetais de interesse destacamos a atemoia, um hibrido de Annona cherimola, Mill e Annonas quamosa, L. Objetivo: Caracterizar o extrato alcoólico bruto de folhas da atemoia em ensaios fitoquímicos, microbiológicos, citotóxicos e no modelo de peritonite. Método: O extrato de folhas de atemoia foi obtido por percolação, com o uso de 20g de folhas secas e trituradas com 100 ml de álcool de cereais. Na padronização dos extratos foram utilizadas análises de idenficação de componentes químicos, os taninos, flavonoides, saponinas e alcaloides, por meio de difrentes reações químicas e os antioxidantes foram analisados pela atividade do DPPH. Diferentes cepas bacterianas foram avaliadas quanto a sensililidade ao extrato em várias concentrações. A citotoxicidade das diferentes concentrações do extrato também foi analisada por hemólise e pelo teste da membrana corioalantide (CAM). Ainda, a capacidade anti-inflamatória do extrato a 4% foi avaliada na peritonite induzida por endotoxina em ratas. Resultados: As análises fitoquímicas indicaram a presença de alcaloides, taninos e flavonoides e ausência de saponinas além da alta capacidade antioxidante. Na concentração de 100% o extrato inibiu a proliferação de bactérias Gram-positivas e Gram-negativas. Os testes de hemólise e CAM mostraram ausência de citotoxicidade na concentração de 4% e elevada citotoxicidade a partir de 10%. No modelo de peritonite, a administração do extrato na concentração de 4% inibiu a migração de neutrófilos para a cavidade peritoneal. Conclusão: O extrato alcoólico das folhas da atemoia mostra importante perfil anti-inflamatório e antioxidante o que estimula estudos futuros para sua aplicação farmacológica. (AU)

Introduction: The alcohol extracts of plants with medicinal potential have compounds with high anti-inflammatory potential and therapeutic application. Among the plant species of interest, we highlight athemoia, a hybrid of Annona cherimola, Mill and Annonas quamosa, L. Objective: To characterize the raw alcoholic extract of athemoious leaves in phytochemical, microbiological, cytotoxic tests and in the peritonitis model. Method: The extract of atemoia leaves was obtained by percolation, with the use of 20g of dried leaves and crushed with 100 ml of cereal alcohol. In the standardization of the extracts were used idenfication analyses of chemical components, tannins, flavonoids, saponins and alkaloids, by means of diffractive chemical reactions and antioxidants were analyzed by DPPH activity. Different bacterial strains were evaluated regarding the sensitivity to the extract in different concentrations. Cytotoxicity of the different concentrations of the extract were also analyzed by hemolysis and by the corioalantide membrane (CAM) test and the anti-inflammatory capacity of the 4% extract was evaluated in endotoxin-induced peritonitis in rats. Results: Phytochemical analysis indicated the presence of alkaloids, tannins and flavonoids and absence of saponins and high antioxidant capacity. At 100% concentration the extract inhibited the proliferation of gram-positive and gram-negative bacteria. Hemolysis and CAM tests showed no cytotoxicity at 4% concentration and high cytotoxicity at 10% level. In the peritonitis model, administration of the extract at the 4% concentration inhibited the migration of neutrophils to the peritoneal cavity. Conclusion: The alcoholic extract of the leaves of athemoia shows an important anti-inflammatory and antioxidant profile which stimulates future studies for its pharmacological application.(AU)

Introducción: Los extractos alcohólicos de plantas con potencial medicinal presentan compuestos con alto potencial antiinflamatorio y aplicación terapéutica. Entre las especies vegetales de interés destacamos la atemoya, un híbrido de Annona cherimola, Mill y Annonas quamosa L. Objetivo: Caracterizar el extracto alcohólico crudo de hojas de atemoya en ensayos modelo fitoquímicos, microbiológicos, citotóxicos y de peritonitis. Método: El extracto de hojas de atemoya se obtuvo por percolación, utilizando 20g de hojas secas y trituradas con 100 ml de alcohol de grano. En la estandarización de los extractos se utilizaron análisis para identificar componentes químicos, taninos, flavonoides, saponinas y alcaloides, a través de diferentes reacciones químicas y los antioxidantes fueron analizados por la actividad de DPPH. Se evaluó la sensibilidad al extracto de diferentes cepas bacterianas a diferentes concentraciones. También se analizó la citotoxicidad de las diferentes concentraciones del extracto por hemólisis y por el test de membrana de corioalantida (CAM) y se evaluó la capacidad antiinflamatoria del extracto al 4% en peritonitis inducida por endotoxinas en ratas. Resultados: Los análisis fitoquímicos indicaron la presencia de alcaloides, taninos y flavonoides y la ausencia de saponinas y alta capacidad antioxidante. A una concentración del 100%, el extracto inhibió la proliferación de bacterias Gram-positivas y Gram-negativas. Las pruebas de hemólisis y CAM no mostraron citotoxicidad a una concentración del 4% y alta citotoxicidad a partir del 10%. En el modelo de peritonitis, la administración del extracto a una concentración del 4% inhibió la migración de neutrófilos a la cavidad peritoneal. Conclusión: El extracto alcohólico de hojas de atemoya muestra un importante perfil antiinflamatorio y antioxidante, lo que estimula futuros estudios para su aplicación farmacológica.(AU)

Effect of piperlongumine during exposure to cigarette smoke reduces inflammation and lung injury.

Chronic obstructive pulmonary disease (COPD) is related to smoking and anti-inflammatory therapy is indicated. Among the mediators with anti-inflammatory properties, we highlight piperlongumine (PL), an alkaloid/amide of Piper longum. Here we evaluated the PL administration on an experimental model of respiratory inflammation resulting from exposure to cigarette smoke. Male Balb/c mice were exposed to burning of 10 commercial cigarettes, 2x/day, for five weeks on specific equipment. PL efficacy was evaluated in control, exposed to smoke without treatment and PL treated (2.0 mg/kg, 3x/week) groups. Animals were weighed and plethysmographic analyses performed at the end of the exposure protocol. Inflammatory cells were evaluated in the bronchoalveolar lavage (BAL) and hemoglobin and glucose in the blood. Lung fragments were processed for histopathological studies and AnxA1, COX-2, NF-kB and neutrophil elastase expressions. Plethysmography revealed that PL maintained pulmonary frequency, volume and ventilation parameters similar to controls, with respiratory volume reduction compared to untreated animals. Final weight was reduced in both exposed groups. PL decreased hemoglobin concentration, attenuated the reduction of glucose levels and reduced influx of lymphocytes, neutrophils and macrophages in BAL. Histopathologically occured infiltration of inflammatory cells, increase of the interalveolar septa and intra-alveolar spaces in untreated animals. But, PL administration recovered lung tissues and, immunohistochemically, promoted increased expression of AnxA1 and reduction of COX-2, NF-kB and neutrophil elastase. Together the results indicate that PL attenuates systemic and pulmonary inflammatory changes, partially by modulating the expression the endogenous AnxA1, and may represent a promising therapy in preventing the inflammation induced by cigarette smoke.

Epidemiologia do câncer no sistema de saúde pública de Catanduva, São Paulo, Brasil / Epidemiology of cancer in the public health system of Catanduva, São Paulo, Brazil / Epidemiología del cáncer en el sistema de salud pública de Catanduva, São Paulo, Brasil

Introdução: As neoplasias malignas representam enorme demanda em saúde pública, devido a sua alta taxa de morbidade e mortalidade, associada à alta incidência e prevalência no Brasil e no mundo. O câncer tem vários fatores de risco que fazem com que os grupos populacionais exibam diferentes padrões de incidência. Esses padrões geralmente estão associados a hábitos e exposição ambiental. Objetivo: Conhecer o perfil epidemiológico de cânceres malignos da cidade de Catanduva e microrregião, estado de São Paulo, Brasil. Método: Os dados foram obtidos dos diagnósticos confirmados de cânceres malignos a partir de biópsias realizadas pelo sistema público de saúde da cidade de Catanduva e da sua região de abrangência, analisados e comparados com dados das demais regiões brasileiras e mundiais. Resultados: Diferentes padrões para idade, sexo e tipos de câncer foram encontrados, como menor incidência de tumores de próstata, colo do útero e pulmão comparados ao perfil nacional. Em contraste, melanoma e câncer de útero tiveram maior incidência. Conclusão: Esses dados revelam uma distribuição epidemiológica distinta, possivelmente explicada pelas características socioeconômicas e ambientais da região e poderão auxiliar a formular políticas de saúde adequadas a essa realidade.(AU)

Introduction: Malignant neoplasms represent a huge demand in public health, due to their high rate of morbidity and mortality, associated with the high incidence and prevalence in Brazil and worldwide. Cancer has several risk factors that cause population groups to exhibit different patterns of incidence. These patterns are usually associated with environmental exposure and habits. Objective: To know the epidemiological profile of malignant cancers in the city of Catanduva and micro-region, state of São Paulo, Brazil. Method: Data were obtained from confirmed diagnoses of malignant cancers based on biopsies performed by the public health system in the city of Catanduva and its region of coverage, analyzed and compared with data from other Brazilian and world regions. Results: Different patterns for age, sex and types of cancer were found, such as a lower incidence of prostate, cervical and lung tumors compared to the national profile. In contrast, melanoma and uterine cancer had a higher incidence. Conclusion: These data reveal a distinct epidemiological distribution, possibly explained by the socioeconomic and environmental characteristics of the region and may help to formulate health policies appropriate to this reality.(AU)

Introducción: Las neoplasias malignas representan una gran demanda de salud pública debido a su alta tasa de morbilidad y mortalidad, vinculada con una alta incidencia y prevalencia en Brasil y en todo el mundo. El cáncer tiene numerosos factores de riesgo, lo que hace que los grupos de población exhiban diferentes patrones de incidencia. Tales patrones se asocian generalmente con los hábitos y la exposición ambiental. Objetivo: Conocer el perfil epidemiológico de cánceres malignos de la ciudad de Catanduva y microrregión, estado de São Paulo, Brasil. Métodos: Los datos fueron obtenidos de los diagnósticos confirmados de cánceres malignos a partir de biopsias realizadas por el sistema público de salud de la ciudad de Catanduva y de su región de alcance, analizados y comparados con datos de las demás regiones brasileñas y mundiales. Resultados: Diferentes patrones para edad, sexo y tipos de cáncer se encontraron, como menor incidencia de tumores de próstata, cuello de útero y pulmón comparados al perfil nacional. En contraste, el melanoma y el cáncer de útero tuvieron mayor incidencia. Conclusión: Estos datos revelan una distribución epidemiológica distinta, posiblemente explicada por las características socioeconómicas y ambientales de la región y podrán auxiliar a formular políticas de salud adecuadas a esa realidad.(AU)

Modulation of the endogenous Annexin A1 in a cigarette smoke cessation model: Potential therapeutic target in reversing the damage caused by smoking?

BACKGROUND: Smoking cessation may help in the reversal of inflammation and damage caused by smoking. The endogenous annexin A1 (AnxA1) protein has anti-inflammatory effects which instigates the understanding of its role in the attenuation of inflammatory processes caused by smoking. MATERIAL AND METHODS: Wistar rats were exposed to cigarette smoke for 8 weeks. After the exposure period, one of the groups remained other 8 weeks in the absence of smoke. Animals not exposed to smoke were used as control. Blood, trachea and lungs were obtained for histopathological, immunohistochemical and biochemical analyses. RESULTS: Loss of cilia of the tracheal lining epithelium was found by smoke exposure, but smoking cessation led to recovery of the tracheal epithelium. Similarly, chronically exposed-to-smoke animals showed increased lymphocytes and macrophages in bronchoalveolar lavage and higher levels of glucose and gamma-GT in their blood. Reduction of lymphocytes, glucose and gamma-GT occurred after smoking cessation. In addition, IL-1ß, IL-6, IL-10, TNF-α and MCP-1 levels were elevated by smoke exposure. Smoking cessation significantly reduced the levels of IL-1ß, IL-6 and MCP-1 but increased the IL-10 concentration. Numerous mast cells and macrophages were observed in the lung of chronically exposed-to-smoke animals with reduction by smoking cigarette abstinence. AnxA1 increased expression and concomitant NF-κB reduction were found in the smoking cessation group. CONCLUSION: Our results showed that cigarette abstinence promoted partial recovery of the inflammatory process. The attenuation of the inflammatory profile may be associated with the overexpression of AnxA1 protein.

Expression of the Annexin A1 and its correlation with matrix metalloproteinases and the receptor for formylated peptide-2 in diffuse astrocytic tumors.

Astrocytomas represent the majority of cerebral gliomas. Studies show that the anti-inflammatory protein Annexin-A1 (ANXA1) is associated with the tumor invasion process and that its actions can be mediated by the receptor for formylated peptides (FPR). Therefore, we evaluated the expression of ANXA1, the receptor FPR2 and matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) in brain astrocytomas. Detection of proteins was performed in sections of diffuse astrocytomas (grade II), anaplastic astrocytomas (grade III) and glioblastomas (GBM, grade IV) and quantifications were made by densitometry. Our analyses showed increased expression of ANXA1 in astrocytomas of all grades, but especially in GBM. The expression of FPR2 is similar to that found for ANXA1, being higher in GBM. Immunostaining for MMPs is also stronger as the degree of malignancy increases, especially with respect to MMP-9. The positive correlation between ANXA1/FPR2 and ANXA1/MMP-9 was observed in all tumors studied. The data indicate the possible action of ANXA1 and FPR2 on the development and progression of astrocytomas, related to increased expression of MMP-9. Thereby, ANXA1 and FPR2 are involved in the biology and malignancy of diffuse astrocytic tumors.

Mimetic peptide AC2-26 of annexin A1 as a potential therapeutic agent to treat COPD.

Chronic obstructive pulmonary disease (COPD) is related to inflammatory process caused by smoking habit. In this scenario, the anti-inflammatory protein Annexin A1 (AnxA1) may represent a therapeutic alternative. We performed experiments to evaluate the effects of the AnxA1 mimetic peptide Ac2-26 in an initial COPD model by physiological, histopathological, biochemical and immunohistochemical analyses. Weight loss, increased blood pressure, reductions in the pulmonary frequency and ventilation, loss of tracheal cilia, enlargement of the pulmonary intra-alveolar spaces and lymphoid tissue found in untreated smoke-exposed group were attenuated by AnxA1 peptide treatment. The Ac2-26 administration also protected against leukocytes influx in bronchoalveolar lavage (BAL), lung and trachea, and it also led to decreased hemoglobin, glucose, cholesterol, gamma glutamyl transferase and aspartato aminotransferase levels. Similarly, reduction of proinflammatory mediators and higher concentration of anti-inflammatory cytokine were found in macerated lung supernatant, blood plasma and BAL in the treated animals. Besides Ac2-26 group showed reduced tissue expressions of AnxA1, cyclooxygenase-2 and metalloproteinase-9, but formylated peptide receptor 2 (FPR2) overexpression. Our results all together highlighted the protective role of the Ac2-26 mimetic peptide in COPD with promising perspectives.

Anti-inflammatory actions of herbal medicines in a model of chronic obstructive pulmonary disease induced by cigarette smoke.

The effects of four medicinal herbs (Arctium lappa, Plantago major, Mikania glomerata Spreng and Equisetum arvense) with anti-inflammatory properties were evaluated in a chronic obstructive pulmonary disease (COPD) model. Wistar rats were exposed to cigarette smoke during 8 weeks and one of the groups was orally given a solution containing 4% of each alcoholic herbal extracts during the exposure period. Control group was not exposed to smoke or treated. Histopathological, immunohistochemical and biochemical analyzes were performed. Normal blood plasma levels of gamma glutamyl transferase indicated no toxicity of the administered herbal extracts. The treatment reduced leukocytes influx in bronchoalveolar lavage, mast cell and macrophages numbers in lungs, as well as prevented pulmonary congestion and tracheal metaplasia. Herbal mixture also decreased plasma inflammatory mediator levels and pulmonary expression of annexin A1 and nuclear factor-k?. Our data indicate synergistic and protective effects of the used herbal medicines in animals exposed to cigarette smoke as a potential therapeutic strategy.

Avaliação da atividade antimicrobiana e citotoxicidade hemolítica em diferentes extratos vegetais / Evaluation of antimicrobial activity and hemolytic cytotoxicity in different plant extracts

Introdução: A busca por novos agentes terapêuticos tem incentivado as pesquisas com plantas medicinais, pois muitas delas podem apresentar propriedade antimicrobiana e conhecer o potencial citotóxico dos extratos é fundamental para garantir a segurança durante o uso. Objetivo: Avaliar a atividade antimicrobiana e a citotoxicidade hemolítica de Arctium lappa (bardana), Equisetum arvense (cavalinha), Mikania glomerata (guaco), Morus nigra (amora) e Plantago major (tanchagem), amplamente consumidos pela população na forma de chás medicinais. Material e Métodos: Os extratos etanólicos fora preparados a 20% por percolação. Na avaliação antimicrobiana foi utilizada a técnica de difusão em disco, empregando as bactérias Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobactersp, Enterococcus sp e Salmonella sp. O ensaio de citotoxicidade baseou-se na exposição dos extratos a 5%, 25%, 50%, 75% e 100% em suspensão de hemácias a 37ºC por 30 minutos, seguido de centrifugação e visualização do grau de hemólise. Resultados: Todos os extratos apresentaram inibição de crescimento microbiano, principalmente sobre Acinetobacter sp (amora), Enterococcus sp (amora e cavalinha), K. pneumoniae(amora, bardana e guaco), P. aeruginosa (cavalinha, tanchagem, bardana e guaco) e Salmonellasp (amora e bardana). No ensaio de citotoxicidade, o grau de hemólise foi classificado como baixo para tanchagem e bardana (5%) e médio para cavalinha, guaco e amora (25%) nas concentrações testadas. Conclusão: Os resultados mostram o potencial antimicrobiano dos extratos de amora, bardana, cavalinha, guaco e tanchagem contra bactérias Gram negativas e a baixa citotoxicidade hemolítica confirma a segurança no uso dos mesmos como agentes terapêuticos.

Expression profiles of Annexin A1, formylated peptide receptors and cyclooxigenase-2 in gastroesophageal inflammations and neoplasias.

The anti-inflammatory protein Annexin-A1 (ANXA1) is associated to tumor invasion process and its actions can be mediated by formylated peptides receptors (FPRs). Therefore, we evaluated the expression and correlation of ANXA1, FPR and cyclooxygenase-2 (COX-2) enzyme in esophageal and stomach inflammations and neoplasias. The study of proteins was performed by immunohistochemistry in biopsies of esophagitis, Barrett's esophagus, squamous cell carcinoma and adenocarcinoma of the esophagus, as well as gastritis, stomach polypus and gastric adenocarcinoma. The intensity of the expressions was evaluated by densitometry. The immunohistochemical and densitometric analyzes showed specificity for the FPR1 receptor and modulation of the ANXA1, COX-2 and FPR1 expressions in the epithelial cells in the different studied conditions. Increased immunoreactivity of these proteins was observed in cases of inflammation and stomach polypus. Interestingly, moderate immunoreactivity for ANXA1 and FPR1 but increased immunolabeling for COX-2 were observed in Barrett́s esophagus and esophageal adenocarcinomas. Also, there was reduced expression of ANXA1 and FPR1 in esophageal carcinoma but COX-2 overexpression in this tumor. There was no expression of FPR2 but ANXA1 and FPR1 expressions were positively correlated in all clinical conditions studied. Positive correlation between ANXA1 and COX-2 were also observed in inflammation conditions while negative correlation between ANXA1 and COX-2 was observed in esophageal carcinoma. Our results demonstrate the unregulated expression of ANXA1 and COX-2 in precursor lesions of esophageal and stomach cancers, reinforcing their involvement in gastroesophageal carcinogenesis. In addition, the data show that the actions of ANXA1 in the inflammatory and neoplastic processes of the esophagus and stomach are specifically mediated by the FPR1 receptor.

Heterogeneity of mast cells and expression of Annexin A1 protein in a second degree burn model with silver sulfadiazine treatment.

Mast cells (MCs) participate in all stages of skin healing and one of their mediators is the Annexin A1 protein (AnxA1), linked to inflammation, proliferation, migration and apoptosis processes, but not studied in thermal burns yet. Therefore, our objectives were to evaluate the behavior of MCs and AnxA1 in a second degree burn model, treated or not with silver sulfadiazine 1% (SDP 1%) and associated to macrophages quantification and cytokines dosages. MCs counts showed few cells in the early stages of repair but increased MCs in the final phases in the untreated group. The normal skin presented numerous tryptase-positive MCs that were reduced after burning in all analyzed periods. Differently, few chymase-positive MCs were observed in the early stages of healing, however, increased chymase-positive MCs were found at the final phase in the untreated group. MCs also showed high immunoreactivity for AnxA1 on day 3 in both groups. In the tissue there was a strong protein expression in the early stages of healing, but in the final phases only in the SDP treated animals. TNF-α, IL-1ß, IL-6, IL-10 and MCP-1 levels and macrophages quantification were increased in inflammation and reepithelialization phases. Reduced IL-1ß, IL-6 and IL-10 levels and numerous macrophages occurred in the treated animals during tissue repair. Our results indicate modulation in the profile of MCs and AnxA1expression during healing by the treatment with SDP 1%, pointing them as targets for therapeutic interventions on skin burns.