Protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism.@*METHODS@#A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats.@*RESULTS@#Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05).@*CONCLUSIONS@#Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.

Otimização de método extrativo para raízes de Arctium lappa L / Extractive method optimization for Arctium lappa l. Roots / Optimización de un método de extracción de raíces de Arctium lappa L

Arctium lappa L. é indicada no Formulário de Fitoterápicos da Farmacopeia Brasileira para o tratamento de distúrbios urinários leves. Estudos já demonstraram o potencial antioxidante, anti-inflamatório e antidiabético deste extrato, onde foram identificados fenóis, lignanas, taninos e flavonoides. O objetivo deste trabalho foi otimizar o método extrativo de raízes de A. lappa. Realizou-se o preparo de extratos por diferentes métodos: Ultrassom, Soxhlet, maceração e turbo extração. A otimização foi realizada por turbo extração seguindo um planejamento fatorial 23, empregando como fatores: teor alcoólico, concentração da matéria prima e tempo de extração. Os extratos foram avaliados quanto ao resíduo seco, teores de fenóis e flavonoides, e atividade antioxidante. Com relação ao resíduo seco, e aos teores de fenóis e flavonoides, os métodos de ultrassom e turbo extração demonstraram melhor poder extrativo. Devido ao menor tempo e custo operacional, a otimização foi realizada por turbo extração, e o extrato otimizado foi obtido utilizando álcool 60%, em proporção matéria prima solvente 1:10 e tempo de extração de 15 minutos. Estas análises poderão nortear futuros testes de transposição de método para escala industrial, diminuindo mão de obra, tempo e custos, visando obter produtos fitoterápicos mais eficientes, com valor acessível à população.

Arctium lappa L. is indicated in the Brazilian Pharmacopeia Herbal Medicines Form for the treatment of mild urinary disorders. Studies have already demonstrated the antioxidant, anti-inflammatory and antidiabetic potential of this extract, where phenols, lignans, tannins and flavonoids were identified. The objective of this work was to optimize the extractive method of A. lappa roots. Extracts were prepared by different methods: Ultrasound, Soxhlet, maceration and vortical extraction. The optimization was performed by vortical extraction following a 23 full factorial design, using as factors: alcohol content, drug concentration and extraction time. The extracts were evaluated for dry residue, phenols and flavonoids contents, and antioxidant activity. Regarding the dry residue, and the phenols and flavonoids contents, the ultrasound and vortical extraction methods showed better extractive power. Due to the lower operating time and cost, the optimization was performed by vortical extraction, and the optimized extract was obtained using 60% alcohol, in a 1:10 drug solvent ratio and extraction time of 15 minutes. These assessments guide the future tests of transposition of the method to an industrial scale, reducing manpower, time and costs, aiming to obtain more efficient phytotherapic products, with affordable value for the population.

Arctium lappa L. está indicado en la Formulacao de Fitoterápicos da Farmacopeia Brasileira para el tratamiento de trastornos urinarios leves. Los estudios han demostrado el potencial antioxidante, antiinflamatorio y antidiabético de este extracto, donde se identificaron fenoles, lignanos, taninos y flavonoides. El objetivo de este trabajo fue optimizar el método extractivo de las raíces de A. lappa. Los extractos se prepararon por diferentes métodos: Ultrasonido, Soxhlet, maceración y turboextracción. La optimización se realizó mediante turboextracción siguiendo una planificación factorial de 23, empleando como factores: tenor alcohólico, concentración de materia prima y tiempo de extracción. Se evaluaron los extractos para determinar el residuo seco, el contenido de fenoles y flavonoides y la actividad antioxidante. En cuanto al contenido de residuo seco, fenoles y flavonoides, los métodos de extracción por ultrasonidos y turbo demostraron un mejor poder de extracción. Debido al menor tiempo y coste operativo, la optimización se realizó mediante turboextracción, y el extracto optimizado se obtuvo utilizando alcohol 60%, en proporción disolvente-materia 1:10 y tiempo de extracción de 15 minutos. Estos análisis podrán orientar futuros ensayos de transposición del método para escala industrial, reduciendo mano de obra, tiempo y costes, con el objetivo de obtener productos fitoterapéuticos más eficientes, con valor accesible para la población.

The preventive effect of taxifolin on acrylamide-induced heart damage in rats / O efeito preventivo da taxifolina em danos cardíacos induzidos por acrilamida em ratos

ABSTRACT Objective Acrylamide is a toxic compound widely used in industrial sectors. Acrylamide causes reactive oxygen species formation and the subsequent lipid peroxidation reaction, which plays an important role in the pathogenesis of oxidative damage. Taxifolin is a flavonoid with antioxidant properties that inhibit reactive oxygen species formation. In this study, we aimed to investigate the preventive effect of taxifolin on acrylamide-induced oxidative heart damage. Methods The rats were divided into three groups: Acrylamide, Acrylamide+Taxifolin , and Healthy group. Water and food intake and body weight alterations were recorded daily. Malondialdehyde, total glutathione, nuclear factor kappa-B, total oxidant status, and total antioxidant status levels were analyzed from the heart tissue. Troponin-I levels, the parameter known as a cardiac biomarker, were analyzed from the blood sample. The cardiac histopathologic examination was also performed. Results In the Acrylamide group animals, the malondialdehyde, nuclear factor kappa-B, total oxidant status, and troponin-I levels were significantly higher compared to the ones of Acrylamide+Taxifolin and Healthy groups. The levels of total glutathione and total antioxidant status were significantly lower compared to Acrylamide+Taxifolin and Healthy groups'. Additionally, in the Acrylamide group, body weight gain, food and water intake, significantly declined compared to the Acrylamide+Taxifolin and Healthy groups. However, in the Acrylamide+Taxifolin group, taxifolin supplementation brought these values close to Healthy group ones. Furthermore, taxifolin treatment ameliorated structural myocardial damage signs induced by acrylamide. Conclusion Acrylamide exposure significantly induced oxidative damage to rat heart tissue. Taxifolin was able to improve the toxic consequences of acrylamide biochemically and histopathologically, possibly due to its antioxidant properties.

RESUMO Objetivo A acrilamida é um composto tóxico amplamente utilizado em setores industriais. Ela causa a formação de reativas de oxigênio e subsequente reação de peroxidação lipídica, que desempenham um papel importante na patogênese do dano oxidativo. A taxifolina é um flavonóide com propriedades antioxidantes que inibe a formação de reativas de oxigênio. Neste estudo, o objetivo foi investigar o efeito preventivo da taxifolina no dano cardíaco oxidativo induzido por acrilamida. Métodos Os ratos foram divididos em três grupos: Acrilamida, Acrilamida+Taxifolina e grupo Saudável. Ingestão de água e comida e alterações de peso corporal dos animais foram registradas diariamente. Malondialdeído, glutationa total, fator nuclear kappa-B, estado oxidante total e estado antioxidante total foram analisados no tecido cardíaco dos ratos. Os níveis de troponina-I, - parâmetro conhecido como biomarcador cardíaco, foram analisados a partir de amostra de sangue. Um exame histopatológico cardíaco também foi realizado. Resultados Nos animais do grupo Acrilamida, os níveis de malondialdeído, fator nuclear kappa-B, estado oxidante total e troponina-I foram significativamente maiores em comparação com os do grupo Acrilamida+Taxifolina e Saudável. Os níveis de glutationa total e estado antioxidante total foram significativamente mais baixos em comparação com grupos Acrilamida+Taxifolina e Saudável. Além disso, no grupo Acrilamida, o ganho de peso corporal e a ingestão de alimentos e água diminuíram significativamente em comparação com os animais dos grupos Acrilamida+Taxifolina e Saudável. No entanto, no grupo Acrilamida+Taxifolina, a suplementação com taxifolina aproximou esses valores aos do grupo Saudável. Além disso, o tratamento com taxifolina melhorou os sinais de dano miocárdico estrutural induzidos pela acrilamida. Conclusão A exposição à acrilamida induziu significativamente o dano oxidativo do tecido cardíaco dos ratos. A taxifolina foi capaz de melhorar as consequências tóxicas da acrilamida bioquímica e histopatologicamente, possivelmente devido às suas propriedades antioxidantes.

Extract from Arrabidaea chica (Fridericia chica) leaves show preventive action for the mitigation of doxorubicin-induced cardiotoxicity / [Extrato das folhas de Arrabidaea chica (Fridericia chica) mostrou potencial ação no combate à cardiotoxicidade induzida pela doxorrubicina]

A doxorrubicina (dox) é um medicamento antineoplásico que induz cardiotoxicidade por estresse oxidativo. Os flavonoides são antioxidantes extraídos de plantas como Camellia sinensis e Arrabidaea chica (Fridericia chica). Esta pesquisa objetivou avaliar efeitos protetores do extrato de A. chica (AC), comparado ao de C. sinensis (CS), frente ao estresse oxidativo induzido pela dox, no coração. Cardiomiócitos e células neoplásicas MDA-MB 231 foram incubados com AC e CS. Depois, adicionou-se dox e avaliaram-se taxas de viabilidade e morte celular. A citometria de fluxo para o ensaio de iodeto de propídeo (IP) em cardiomiócitos mostrou as seguintes taxas de morte celular: controle 53%; dox 78% (maior que controle, P=0,015); AC_12,5µg/mL + dox 65% (menor que dox, P=0,031); AC_25µg/mL + dox 62% (menor que dox, P=0,028); AC_50µg/mL + dox 63% (menor que dox, P=0,030); CS_12,5µg/mL + dox 71% (menor que dox, P=0,040); CS_25µg/ml + dox 69% (menor que dox, P=0,037); CS_50µg/mL + dox 74% (menor que dox, P=0,044). Resultados das células MDA-MB 231 mostraram que nenhum extrato interferiu na atividade antitumoral da dox. Os dados de IP foram corroborados pelos de MTT. Este estudo reporta promissora utilização de A. chica na prevenção da cardiotoxicidade induzida pela dox.(AU)

In Silico Screening of DNA Gyrase B Potent Flavonoids for the Treatment of Clostridium difficile Infection from PhytoHub Database

Abstract Clostridium difficile infection (CDI) is the most common hospital acquired diarrheal disease with its increasing incidence and mortality rate globally. DNA Gyrase B (GyrB) is a key component of DNA replication process across all bacterial genera; thus, this offers a potential target for the treatment of CDI. In the present study, several virtual screening approaches were employed to identify a novel C. difficile GyrB inhibitor. The 139 known metabolites were screened out from the 480 flavonoids in PhytoHub database. Molinspiration and PROTOX II servers were used to calculate the ADME properties and oral toxicity of the metabolites, whereas mutagenicity, tumorigenicity, irritant, and reproductive effect were predicted using DataWarrior program. The binding mode and the binding efficiency of the screened flavonoids against the GyrB were studied using FlexX docking program. From virtual screening of 139 metabolites, we found 25 flavonoids with no mutagenicity, tumorigenicity, irritant, and reproductive effect. Docking study suggested that flavonoids 1030 ((-)-epicatechin 3'-O-sulfate), 1032 ((-)-epicatechin 4'-O-sulfate), 1049 (3'-O-methyl-(-)-epicatechin 4-O-sulfate), 1051 (3'-O-methyl-(-)-epicatechin 7-O-sulfate), 1055 (4'-O-methyl-(-)-epicatechin 7-O-sulfate) and 1317 (quercetin sulfate) have significantly higher binding affinity than the known GyrB inhibitor novobiocin. The results from molecular dynamics simulation and free energy calculations based on solvated interaction energy suggested that (-)-epicatechin 3'-O-sulfate could be a potential drug candidate in the management of CDI.

Citotoxicidade e efeito indutor de mineralização de flavonoides sobre células osteoblásticas / Cytotoxicity and inducing effect of mineralization of flavonoids on osteoblastic cells

A perda óssea dentária e a formação de lesões periapicais surgem como uma consequênc ia do desequilíbrio da homeostase óssea. Os osteoblastos, juntamente com os osteoclastos e osteócitos, atuam na formação e na reabsorção óssea. Vários marcadores de formação óssea são produzidos por osteoblastos ativos e refletem diferentes aspectos da dif erenciação osteoblástica e da remodelação óssea. Com isso, muitos autores têm explorado o uso de fitoterápicos, visando obter novos compostos que apresentem propriedades terapêuticas, como os flavonoides, e que estimulem a neoformação óssea e o reparo da r egião periapical. O objetivo deste estudo foi avaliar in vitro a citotoxicidade e efeito indutor de mineralização de flavonoides sobre células osteoblásticas humanas. Para isso, células osteoblásticas da linhagem Saos expostas aos seguintes flavono2 foram ides: quercetina, miricetina e seus derivados taxifolina, isoquercitrina, rutina, ampelopsina e EGCG, além de pinocembrina, crisina e canferol, de forma isolada e combinada. Foi avaliado o efeito citotóxico, a atividade de fosfatase alcalina e indução de n mé todo de Shapiroódulos de mineralização. Os resultados foram analisados p elo Wilk, e as variáveis foram submetidas à análise de ANOVA seguida pelo teste de Tukey para comparar entre os grupos e/ou concentrações ou teste de Dunnett para comparar entre cada grupo e o controle, com nível de significância de 5%. A viabilidade da cultura de osteoblastos não teve uma redução estatisticamente significativa na presença da maioria dos compostos, exceto crisina a 100µM. Taxifolina, isoquercitrina, rutina, ampelopsina e EGCG foram os compostos que estimularam significativamente a atividade da fosfatase alcalina, juntamente com as combinações taxifolina+isoquercitrina, taxifolina+ampelopsina e taxifolina+rutina a 25/25 µM. Quanto a formação de nódulos de mine ralização, ampelopsina, isoquercitrina, rutina, pinocembrina e miricetina isolados e taxifolina+isoquercitrina, taxifolina+ampelopsina e taxifolina+rutina combinados obtiveram os melhores resultados, variando de acordo com as concentrações. Concluise que a taxifolina, isoquercitrina, rutina e ampelopsina e combinações de taxifolina com esses flavonoides são citocompatíveis e apresentam efeito indutor de mineralização em osteoblastos Saos-2(AU)

Dental bone loss and the formation of periapical lesions arise as a consequence of imbalance of bone homeostasis. Osteoblasts, together with osteoclasts and osteocytes, act in bone formation and resorption. Several markers of bone formation are produced by active osteoblasts and reflect different aspects of osteoblastic differentiation and bone remodeling. Thus, many authors have explored the use of phytotherapics in order to obtain new compounds with therapeutic properties, such as flavonoids, and also stimulate bone neoformation and periapical region repair. The objective of this study was to evaluate in vitro the cytotoxicity and inducing effect of flavonoid mineralization on human osteoblastic cells. For this, osteoblastic cells of the Saos-2 lineage were exposed to the following flavonoids: quercetin, myricetin and its derivatives taxifoline, isoquercitrin, rutin, ampelopsin and EGCG, in addition to pinocembrin, chrysin and kaempferol, in an isolated and combined manner. The cytotoxic effect, the activity of alkaline phosphatase and the induction of mineralization nodules were evaluated. The results were analyzed using the Shapiro-Wilk method, and the variables were submitted to ANOVA analysis followed by the Tukey test to compare between groups and/or concentrations or Dunnett's test to compare between each group and the control, with a level of 5% significance. The viability of the osteoblast culture did not have a statistically significant reduction in the presence of most compounds, except 100 µM chrysin. Taxifoline, isoquercitrin, rutin, ampelopsin and EGCG were the compounds that significantly stimulated the activity of alkaline phosphatase, together with the combinations taxifoline+isoquercitrin, taxifoline+ampelopsin and taxifoline+rutin at 25/25 µM. As for the formation of mineralization nodules, ampelopsin, isoquercitrin, rutin, pinocembrin and myricetin alone and taxifoline+isoquercitrin, taxifoline+ampelopsin and taxifoline+rutin combined obtained the best results, varying according to the concentrations. It is concluded that taxifoline, isoquercitrin, rutin and ampelopsin and combinations of taxifolin with these flavonoids are cytocompatible and have a mineralization-inducing effect on Saos-2 osteoblasts(AU)

Optimization of extraction of flavonoids from Lonicera rupicola and analysis of its effects in resisting inflammation, relieving pain, enhancing immunity, and inhibiting pyroptosis / 中国中药杂志

The present study optimized the extraction of flavonoids from Lonicera rupicola Hook. f. et Thoms(LRH) and explored its pharmacological effects, such as resisting inflammation, relieving pain, enhancing immunity, and inhibiting pyroptosis, aiming to provide data support and scientific basis for the development and utilization of LRH. Response surface methodology(RSM) was applied to optimize the extraction of flavonoids from LRH based on the results of single-factor experiments. Anti-inflammatory and analgesic effects of LRH flavonoids were evaluated via inflammation and pain models in mice, such as xylene-induced ear swelling, carrageenan-induced footpad swelling, writhing caused by acetic acid, and paw licking. The effect of LRH flavonoids on the carbon clearance index of monocytes and serum immunoglobulin A(IgA) and IgM levels was analyzed on the immunosuppression model induced by cyclophosphamide in mice. The anti-oxidative effect in vivo of LRH flavonoids on liver superoxide dismutase(SOD), catalase(CAT), and malondialdehyde(MDA) levels was determined based on the chronic/subacute aging model in mice induced by D-galactose. The levels of cysteinyl aspartate specific proteinase-1(caspase-1), interleukin-1β(IL-1β), and IL-18 in the supernatant of J774 A.1 mononuclear phagocytes were detected to evaluate the effect of LRH flavonoids on the pyroptosis of mononuclear phagocytes in mice induced by the combination of lipopolysaccharide(LPS) and adenosine triphosphate(ATP). Meanwhile, the effect of LRH flavonoids on the cAMP-PKA signaling pathway was also explored. The optimum conditions for the extraction of LRH flavonoids are listed below: extraction temperature of 65 ℃, the ethanol concentration of 50%, extraction time of 60 min, a material-liquid ratio at 1∶25, and the yield of LRH flavonoids of 0.553%. RSM determined the multiple quadratic regression equation model of response value and variables as follows: the yield of LRH flavonoids=0.61-0.48A+0.1B+0.029C-0.014D+0.32AB+0.04AC-0.012AD-0.02BC+0.037BD-0.031CD-0.058A~2-0.068B~2-0.069C~2-0.057D~2. LRH flavonoids could effectively inhibit ear swelling and footpad swelling, reduced acetic acid-induced writhing, and delayed the paw licking response time in mice. Additionally, LRH flavonoids could improve the carbon clearance index in immunosuppressed mice, potentiate the activities of SOD and CAT and reduce MDA levels in the liver of aging mice induced by D-galactose, and effectively inhibit macrophage pyroptosis by decreasing the levels of caspase-1, IL-1β, and IL-18. The results reveal that LRH flavonoids possess excellent pharmacological activities such as resisting inflammation and oxidation, relieving pain, and enhancing immunity. They can inhibit pyroptosis by enhancing the cAMP-PKA signaling pathway. The results of this study can underpin the pharmacological research, development, and utilization of LRH.

Role of micronize purified flavonoid fraction and ethanol Graptophyllum pictum extract on experimental anal ulcer healing. Study on Wistar rat / Papel da fração flavonoica purificada micronizada e do extrato etanólico de Graptophyllum Pictum em experimento de cicatrização de úlcera anal. Estudo com ratos Wistar

ABSTRACT Aim of the study To evaluate the role of micronized purified flavanoid fraction and ethanol Graptophyllum pictum extract in the treatment of anal ulcer. Method Twenty-eight Wistar rats were randomly allocated into four groups. Groups 2, 3 and 4 the anus were induced with croton oil, but was not induced on group 1. Groups 1 and 2 were treated with normal saline, while groups 3 and 4 were treated with micronized purified flavanoid fraction, and ethanol G. pictum extract, respectively. On 9th days blood sample were taken from the retro-orbital region, and Wistar was killed by cervical dislocation under ether anesthesia. The anal canal was resected up 2 cm from anal opening, weighted, photographically taken to measure the percentage of residual ulcer, and then prepared for microscopic examination. Elisa methods were done for superoxide dismutase and malondialdedhyde. The total leukocyte in the anal specimen was counted under 400 magnification power. superoxide dismutase, anal coefficient, and total leukocyte for statistical analysis were using ANOVA and LSD, while malondialdedhyde and percentage of ulcers were using Kruskal-Wallis and Mann-Whitney. Result Treatment with ethanol G. pictum extract dose of 100 mg/kg BW significantly reduces the percentage of anal ulcer, the edema, leukocyte infiltration, and malondialdedhyde, and increase the superoxide dismutase in comparison without treatment. Treatment with micronized purified flavanoid fraction did not reduce the leukocyte, anal coefficient, and percentage of anal ulcer, only increase malondialdedhyde and decrease superoxide dismutase significantly.

RESUMO Objetivo do estudo Avaliar o papel da Fração Flavonoica Purificada Micronizada e do Extrato Etanólico de Graptophyllum pictum no tratamento de úlcera anal. Método Vinte e oito ratos Wistar foram randomicamente alocados em quatro grupos. Nos grupos 2, 3 e 4, indução com óleo de cróton foi realizada no ânus, excetuando-se o Grupo 1. Os grupos 1 e 2 foram tratados com solução salina normal, enquanto os grupos 3 e 4 foram tratados com fração flavonoica purificada micronizada e extrato etanólico de Graptophyllum pictum, respectivamente. No nono dia, amostras de sangue foram colhidas da região retroorbital, e o rato Wistar sofreu eutanásia por deslocamento cervical sob anestesia com éter. O canal anal foi ressecado até 2 cm da abertura anal, ponderado e fotografado para medir a porcentagem de úlcera residual e, em seguida, preparado para exame microscópico. Os métodos superoxide dismutase e malondialdedhyde do ensaio Elisa foram realizados. A contagem total de leucócitos foi realizada na amostra anal com ampliação de 400 vezes. ANOVA e LSD foram utilizados para a análise estatística de superoxide dismutase, coeficiente anal e número total de leucócitos, enquanto os testes de Kruskal-Wallis e Mann-Whitney foram utilizados para a análise de malondialdedhyde e porcentagem de úlceras. Resultado O tratamento com o extrato etanólico de Graptophyllum pictum (100 mg/kg de peso corporal) reduz de modo significativo a porcentagem de úlceras anais, o edema, a infiltração de leucócitos e o malondialdedhyde e aumenta a superoxide dismutase, comparado ao não tratamento. O tratamento com a fração flavonoica purificada micronizada não reduziu os leucócitos, o coeficiente anal e a porcentagem de úlceras anais, apenas aumentou o malondialdedhyde e diminuiu significativamente a superoxide dismutase.

Association Between Chocolate Consumption and Severity of First Infarction

Abstract Background: Cardiovascular diseases, such as acute myocardial infarction, are the main causes of death in the world. The flavonoids present in chocolate can have benefits for people who have risk factors to the development of cardiovascular diseases and have a coadjuvant effect on known therapies. Objective: To analyze the association between chocolate consumption, severity of coronary lesions, risk factors and severity of the first infarction in patients attended at the Cardiology Institute of Santa Catarina and other hospitals in the State of Santa Catarina. Methods: Subanalysis of the Catarina Heart Study cohort, evaluated 350 patients with first myocardial infarction. We evaluated clinical, echocardiographic, hemodynamic laboratorial variables. We used chi square test to evaluate qualitative variables, t student test in the case of parametric variables and U Mann Whitney test in non-parametric variables. We considered significant p < 0,05. Results: Lower prevalence of hypertension (43.2% % vs. 62.3% p = 0.003), diabetes mellitus (13.5% vs. 25.7%, p = 0.027) and smoking (24.3% vs. 37.7%, p = 0.032) among those who consume chocolate. Higher use of alcohol (40.5% vs. 26.4%, p = 0.018) and drugs (9.5% vs. 3.3%, p = 0.023) among those who consumed chocolate. Among the patients who consumed chocolate, there was a negative correlation between amount consumed and Syntax (r = -0.296, p = 0.019). Conclusion: There was association between chocolate consumption and lower prevalence of hypertension, diabetes and smoking. There was no association between amount of chocolate consumed and post-infarction ventricular function and TIMI frame count. Higher prevalence of alcohol and drug use among those who consume chocolate. Negative correlation between Syntax and the amount of chocolate consumed.

Effects of icariside II on brain tissue oxidative stress and Nrf2/HO-1 expression in rats with cerebral ischemia-reperfusion injury

Abstract Purpose: To investigate the effects of icariside II on brain tissue oxidative stress and Nrf2/HO-1 expression in rats with cerebral ischemia-reperfusion injury (CIRI). Methods: One hundred SD rats were randomly divided into sham-operated, model, and 5, 10 and 20 mg/kg icariside II groups, 20 rats in each group. The middle cerebral artery occlusion model (ischemia for 2 h followed by reperfusion for 24 h) was established in the later 4 groups. In later 3 groups, at reperfusion beginning, the rats were intragastrically administrated with 5, 10 and 20 mg/kg icariside II, respectively. After 24 h of reperfusion, the neurological severity score, cerebral water content and cerebral infarction volume, brain tissue oxidative stress indexes and Nrf2 and HO-1 protein expressions were determined. Results: Compared with model group, in 20 mg/kg icariside II group the neurological severity score, cerebral water content and cerebral infarction volume, brain tissue ROS content and MDA level were significantly decreased (P<0.05), and the brain tissue SOD, GSH-Px and catalase levels and Nrf2 and HO-1 protein levels were significantly increased (P<0.05). Conclusion: Icariside II can alleviate the CIRI in rats through reducing brain tissue oxidative stress and improving Nrf2/HO-1 expression.

The effect of pycnogenol on lymphatic nodes and adhesion during in a peritoneal adhesion model in rats

Abstract Purpose: To investigate the effects of pycnogenol on peritoneal adhesions and additionally to investigate the immunohistochemical effects of free oxygen radicals and reactive lymph nodes detected in the adhesive tissue that was sampled surrounding the cecum on intra-abdominal adhesions. Methods: Twenty-seven Wistar Albino rats were divided into three groups. In group 1 (sham), laparotomy was performed and stitched up. In group 2 (control), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and each rat was intraperitoneally administered 2 cc of saline. In group 3 (experimental), after laparotomy was performed, punctate hemorrhage was induced by cecal abrasion in the cecum and each rat was intraperitoneally administered a sterile Pycnogenol derivative. The rats in all groups were re-laparotomized on postoperative day 7; samples were obtained from the peritoneal tissue surrounding the cecum, and the rats were sacrificed. Results: In group 3, there was a statistically significant difference in terms of inflammation, lymph node size, and free oxygen radicals; these parameters tended to increase. In terms of fibrosis evaluated using H&E and MT, there was no significant difference between groups 2 and 3. Conclusions: No positive outcomes indicating that pycnogenol reduces intra-abdominal adhesions were obtained. However, it caused severe inflammation in the tissue. Moreover, a significant increase in lymph node size was detected secondary to inflammation. Additionally, in immunohistochemical analyses conducted to detect oxidative stress, pycnogenol increased the production of free oxygen radicals in the tissue.

TeleCondutas: hemorroidas / TeleGuides: hemorrhoids

Hemorroidas são coxins vasculares normais do canal anal. São formados por espaços vasculares (sinusoides), tecido elástico e conjuntivo, e músculo liso. Sua função é proteger os esfíncteres anais subjacentes e contribuir para a continência fecal. Reservamos o termo "doença hemorroidária" para quando existem sintomas relacionados à sua presença. É mais prevalente em pessoas com idade entre 45 e 65 anos, tendo como principal causa o esforço evacuatório repetitivo, que determina o estiramento do tecido de sustentação dos plexos. Constipação, esforço evacuatório prolongado e gestação são seus principais fatores de risco. Esta guia apresenta informação que orienta a conduta para casos de hemorroidas no contexto da Atenção Primária à Saúde, incluindo: classificação das hemorroidas, sinais e sintomas, diagnóstico, tratamento da doença hemorroidária na APS, tratamento no serviço especializado, indicação de colonoscopia e encaminhamento para serviço especializado.

Oleanonic acid from Lippia lupulina (Verbenaceae) shows strong in vitro antileishmanial and antitrypanosomal activity / Ácido oleanônico isolado de Lippia lupulina (Verbenaceae) apresenta potentes atividades leishmanicida e tripanocida

Leishmaniasis and Chagas disease affect millions of people in tropical and subtropical regions. Drugs used currently to treat such diseases often present undesirable side effects and low efficiency. The aim of this work was to identify extracts and isolated compounds from the genus Lippia with leishmanicidal and trypanocidal activity. Fifteen extracts from different plant parts of Lippia species with partially known chemical compositions, four partition fractions, six compounds and a mixture of four interconverting flavanones previously isolated from Lippia salviaefolia and Lippia lupulina were assayed in vitro towards epimastigote forms of Trypanosoma cruzi and promastigote forms of Leishmania amazonensis. The root extract of L. lupulina had potent activity against T. cruzi and L. amazonensis (IC50 of 20.0 and 54.5 µg mL-1, respectively). The triterpenoid oleanonic acid showed the strongest activity against these protozoans (IC50 of 18.5 and 29.9 µM, respectively). Our results indicate that Lippia plants and their derivatives deserve further investigation in the search for new antiprotozoal drugs, particularly for the treatment of leishmaniasis and Chagas disease.

Leishmaniose e doença de Chagas afetam milhões de pessoas em regiões tropicais e subtropicais. As drogas atualmente usadas para tratar estas doenças frequentemente apresentam efeitos colaterais indesejáveis e baixa eficiência. Este trabalho teve como objetivo encontrar extratos, frações e compostos isolados de espécies do gênero Lippia com atividades leishmanicida e tripanocida. Quinze extratos de diferentes partes de plantas do gênero Lippia, com composições químicas parcialmente conhecidas, quatro frações de partição, seis substâncias e uma mistura de quatro flavanonas interconversíveis isolados de Lippia salviaefolia e Lippia lupulina foram testados, in vitro, frente a formas epimastigotas de Trypanosoma cruzi e promastigotas de Leishmania amazonensis. O extrato etanólico das raízes de L. lupulina apresentou atividade potente contra T. cruzi e L. amazonensis (IC50 de 20,0 e 54,5 µg mL-1, respectivamente), enquanto que o ácido oleanônico mostrou as atividades mais fortes contra estes protozoários, com IC50 de 18,5 e 29,9 µM, respectivamente. Estes resultados indicam que espécies do gênero Lippia e seus derivados merecem investigações adicionais na busca por novas terapias antiprotozoárias, especialmente para o tratamento de leishmaniose e doença de Chagas.

A single dose of dark chocolate increases parasympathetic modulation and heart rate variability in healthy subjects / Uma única dose de chocolate amargo aumenta a modulação parassimpática e a variabilidade da frequência cardíaca em indivíduos saudáveis

ABSTRACT Objective: The aim of this study was to investigate the acute effect of a single dose of dark chocolate (70% cocoa) on blood pressure and heart rate variability. Methods: Thirty-one healthy subjects (aged 18-25 years; both sexes) were divided into two groups: 10 subjects in the white chocolate (7.4 g) group and 21 in the dark chocolate (10 g) group; measurements were performed at the university's physiology lab. An electrocardiogram measured the sympathovagal balance by spectral and symbolic analysis. Results: A single dose of dark chocolate significantly reduced systolic blood pressure and heart rate. After consuming 10 g of dark chocolate, significant increases were observed for heart rate variability, standard deviation of RR intervals standard deviation of all NN intervals, square root of the mean squared differences between adjacent normal RR intervals root mean square of successive differences, and an increase in the high frequency component in absolute values, representing the parasympathetic modulation. Conclusion: In conclusion the importance of our results lies in the magnitude of the response provoked by a single dose of cocoa. Just 10 g of cocoa triggered a significant increase in parasympathetic modulation and heart rate variability. These combined effects can potentially increase life expectancy because a reduction in heart rate variability is associated with several cardiovascular diseases and higher mortality.

RESUMO Objetivo: O objetivo deste estudo foi investigar o efeito agudo de uma única dose de chocolate amargo (70% cacau) sobre a pressão arterial e a variabilidade da frequência cardíaca. Métodos: Trinta e um indivíduos saudáveis (com idade entre 18-25 anos; ambos os sexos) foram divididos em dois grupos: 10 indivíduos no grupo chocolate branco (7,4 g) e 21 no grupo chocolate amargo (10,0 g); as avaliações foram realizadas no laboratório de fisiologia da Universidade Federal de Ciências da Saúde de Porto Alegre. Resultados: O eletrocardiograma foi realizado para analisar o balanço simpatovagal através da análise espectral e simbólica. Uma única dose de chocolate amargo reduziu significativamente a pressão arterial sistólica e a frequência cardíaca. Depois de consumir 10 g de chocolate amargo, observou-se aumento significativo na variabilidade da frequência cardíaca, o desvio padrão dos intervalos, a raiz quadrada da média do quadrado das diferenças entre os intervalos RR normais adjacentes a raiz quadrada da média da soma dos quadrados das diferenças entre os intervalos NN normais adjacentes e um aumento na componente de alta frequência em valores absolutos, o que representa a modulação parassimpática. Conclusão: Em conclusão, a importância dos resultados aqui apresentados reside na magnitude da resposta provocada por uma dose única de cacau (10 g). Esta provocou um aumento significativo da modulação parassimpática e da variabilidade da frequência cardíaca no coração. Esses efeitos, quando combinados, podem, potencialmente, aumentar a esperança de vida, porque a redução da variabilidade da frequência cardíaca está associada a doenças cardiovasculares e maior mortalidade.

Comparative effects of natural products on ischemia-reperfusion injury: relation to their "in vitro" antioxidant capacity / Efectos comparativos de productos naturales sobre la injuria por isquemia-reperfusión: relación con la capacidad antioxidante ¨in vitro¨

Our aim was to compare the effects of a non-alcoholic Cabernet-Sauvignon (CS), Malbec (M), Merlot blend (BW) red wine extracts, Ilex paraguariensis (Ip) or Ilex brasiliensis (Ib) aqueous extracts, Vaccinium meridionale Swartz (mortiño) fermented extract (FE), berry juice (BJ) and polyphenols-riched fractions of cocoa(PFC) against reperfusion injury. Isolated rat hearts were submitted to 20 min of global ischemia (GI) and 30 min of reperfusion (R). Other hearts were treated 10 min before GI and first 10 min of R with the extracts. CS, M, Ip, Ib and FE attenuated the myocardial dysfunction and oxidative damage whereas BW, BJ and PFC were ineffective. Paradoxically, PFC had the highest and BW similar scavenging activity than protective extracts. The beneficial actions were lost when nitric oxide synthase (NOS) was inhibited. These data indicate that in vitro antioxidant capacity of natural products is not primarily responsible for the cardioprotection being involved NO-dependent pathways.

Nuestro objetivo fue comparar los efectos de extractos no alcohólicos de los vinos tinto Cabernet-Sauvignon (CS), Malbec (M) y Merlot (BW), de extractos acuosos de Ilex paraguariensis (Ip) e Ilex brasiliensis (Ib), de un extracto fermentado (FE) de Vaccinium meridionale Swartz (mortiño), del jugo del mortiño (BJ) y de fracciones enriquecidas en polifenoles de cacao (PFC) sobre las alteraciones miocárdicas producidas por isquemia-reperfusión. Para ello, corazones aislados de rata fueron sometidos a 20 min de isquemia global (GI) y 30 min de reperfusión (R). Otros corazones fueron tratados 10 minutos antes de GI y durante los primeros 10 minutos de la R con los extractos. CS, M, Ip, Ib y FE atenuaron la disfunción contráctil postisquémica y el daño oxidativo mientras que BW, BJ y PFC fueron ineficaces. Paradójicamente, PFC mostró la más alta y BW similar actividad antioxidante que los extractos protectores. Las acciones beneficiosas fueron abolidas cuando la óxido nítrico sintasa (NOS) fue inhibida. Estos datos indican que la capacidad antioxidante in vitro de los productos naturales no es el principal responsable de la cardioprotección estando involucradas vías dependientes del NO.

Isolation of ESBL-producing gram-negative bacteria and in silico inhibition of ESBLs by flavonoids

Objective: To evaluate nosocomial accounts of 426 extended spectrum b-lactamase [ESBL]-producing strains from 705 isolates of 9 pathogenic gram-negative bacteria in vitro. We analysed the genetic divergence of ESBLs by constructing a phylogenetic tree and modelled flavonoid inhibition of ESBLs with in silico molecular docking to determine effective control options

Methods: Nine ESBL-producing bacteria were isolated from urine samples and their antibiograms were determined by the disc-diffusion method. Comparative models of the 9 ESBL enzymes were generated computationally using reference sequences, and validated by Ramachandran plots. Molecular docking with 11 flavonoids was conducted against the ESBL models

Results: Isolated strains were floridly multidrug-resistant. From the docking study, the predicted minimum energy value of amikacin was _8.108 kcal/mol against the wild type TEM-1 ESBL of Acinetobacter baumannii, while the docking value against the mutant type Escherichia coli was _7.388 kcal/mol. The docking scores obtained corroborated the in vitro results showing that the antibiotic was incapable of controlling the ESBL of the mutant strain. Among 11 flavonoids tested against the mutant ESBL of E. coli, epigallocatechin 3-gallate and eriodictyol, with docking scores of _9.448 and _8.161 kcal/ mol, respectively, were the most effective, with druglikeness scores of 0.39 and 1.37, respectively, compared to 1.03 for amikacin

Conclusion: Docking scores and drug-likeness scores indicated that flavonoids are compelling alternative antimicrobial agents that could serve as complementary therapy for newly arising ESBL-producing bacteria

Utilización de propóleos en odontología / The use of propolis in dentistry

El propóleos es un producto natural elaborado por las abejas a partir de la secreción que recogen de ciertas especies vegetales y que, luego de modificarlas con sus secreciones salivares, lo transportan al interior de la colmena. Así, el propóleos es responsable directo de garantizar la asepsia de la colmena. Múltiples investigaciones científicas atribuyeronal propóleos propiedades antioxidantes, antibacterianas, antivirales, fungicidas, cicatrizantes, antiinflamatorias, anestésicas, inmunomoduladoras antitumorales. Asimismo, en bastas investigaciones se comprobó que el propóleos actúa inhibiendo la actividad de los Streptococo mutans, principal microorganismo productor de caries dental. Esto motivó la realización de la presente revisión bibliográfica sobre las propiedades y utilización del propóleos en odontología.

Propolis is a natural product made by bees fromcollecting secretion of certain plant speciesand, after modifying their salivary secretions,transported into the hive. So propolis is directlyresponsible for ensuring the cleanliness of the hive.Multiple scientific research attributed to propolisantioxidant, antibacterial, antiviral, fungicide, healing,anti-inflammatory, anesthetic,immunomodulatory and antitumor properties.Also in rough investigations it was foundthat propolis acts by inhibiting the activityof Streptococcus mutans, the main producingmicroorganism tooth decay. This led to therealization of this literature review on theproperties and use of propolis in dentistry.

Avaliação do uso de flavonoides no tratamento da inflamação / Evaluación del uso del flavonoides en el tratamiento de la inflamación / Evaluation of the flavonoides use in the treatment of the inflammation

A inflamação é considerada uma forma de defesa do nosso organismo, podendo ser desencadeada por vários estímulos. Entretanto, em determinadas situações a resposta pode ser exacerbada e contínua, tornando‒se prejudicial. Os fármacos utilizados atualmente no tratamento dos processos inflamatórios possuem efeitos adversos, sendo os compostos vegetais uma alternativa ao uso destes medicamentos. Um destes compostos são os flavonoides, que apresentam uma série de propriedades farmacológicas, destacando-se a atividade anti-inflamatória. Para a execução deste trabalho foi realizada uma pesquisa nas bases de dados do Google Acadêmico, Scientific Electronic Library Online (SciELO) e Biblioteca Virtual em Saúde (BVS), o recorte temporal usado na pesquisa compreende os anos de 2008 a 2014 e as palavras‒chave utilizadas foram flavonoides, inflamação, flavonoides na inflamação, mediadores inflamatórios e atividade dos flavonoides. Objetiva‒se apresentar diferentes estudos que avaliam a atividade dos flavonoides na inflamação, enfatizando sua ação em mediadores químicos específicos como as citocinas, óxido nítrico e metabólitos do ácido araquidônico. Observa‒se a capacidade dos flavonoides de modular estas substâncias químicas. Quercetina, miricitrina, apigenina, epicatequina, entre outros flavonoides regulam a atividade de enzimas e a síntese de mediadores químicos, responsáveis pela ativação e perpetuação do processo inflamatório, sendo esta a principal maneira com que combatem esta doença(AU)

Inflammation is considered a form of defense of our body and can be triggered by various stimuli. However, in certain situations the answer may be exacerbated and further, becoming harmful. The drugs currently used to treat inflammatory processes have adverse effects, vegetables compounds as an alternative to the use of these drugs. One of these compounds are flavonoids, which exhibit a number of pharmacological properties, especially the anti-inflammatory activity. For the execution of this study a survey was conducted in the databases Google Scholar, Scientific Electronic Library Online (SciELO) and Virtual Health Library (VHL), the time frame used in the research comprises the years 2008-2014 and the keywords used were flavonoids, inflammation, flavonoids in inflammation, inflammatory mediators and activity of flavonoids. The objective was to present different studies evaluating the activity of flavonoids in inflammation, emphasizing its action on specific chemical mediators such as cytokines, nitric oxide and arachidonic acid metabolites. The paper underlined the ability of flavonoids to modulate these chemicals. Quercetin, miricitrin, apigenin, epicatechin, and other flavonoids regulate the activity of enzymes and the synthesis of chemical mediators responsible for the activation and perpetuation of the inflammatory process, which is the main way to fight this disease(AU)

La inflamación es considerada como una defensa del organismo que se activa por diferentes estímulos; em ocasiones puede exacerbarse y causar daño. Los medicamentos actualmente usadas para tratar los procesos inflamatorios presentan efectos adversos, por lo que como una alternativa de uso se pudieran explorar algunas plantas consideradas verduras. Los flavonoides exhiben actividad antiinflamatoria entre otras propiedades farmacológicas. Para la ejecución de este estudio se revisaron las bases de datos de Google Académico, la Biblioteca Electrónica Científica en línea (SciELO) y la Biblioteca de Virtual Salud (BVS), la investigación comprende los años 2008 al 2014 y las palabras clave utilizadas fueron flavonoides, inflamación, flavonoides en la inflamación, mediadores inflamatorios y actividad de flavonoides. El objetivo era localizar estudios que evaluaran la actividad de lós flavonoides en la inflamación, con énfasis en su acción como mediadores químicos específicos como la citocinas, el óxido nítrico y metabolitos del ácido araquidónico. Se resalta la habilidad de lós flavonoides de modular estos químicos. Quercetina, miricitrina, apigenina, epicatequina entre otros flavonoides regulan la actividad de enzimas y la síntesis de mediadores químicos responsable para la activación y perpetuación del proceso inflamatorio que es la manera principal de luchar esta enfermedad(AU).