Research on Anti-inflammatory Targets and Mechanisms of alkaloids in Picrasma quassioides Benn Through Network Pharmacology

Abstract This study aimed to investigate the molecular mechanism of Picrasma quassioides Benn against inflammation by means of network pharmacology. The paper will provide a reference for multi-target and multi-channel treatment of inflammation with traditional Chinese medicine. Through screening and analysis, 11 active ingredients and 109 anti-inflammation prediction targets were obtained and constructed a compound-target network. The targets such as VEGFA, TLR4 and STAT3 may play a crucial role. Network enrichment analysis showed that the 109 potential targets constitute a number of pathways or inflammatory reactions closely related to inflammation, including NF-κB signaling pathway and MAPK signaling pathway. The docking results indicated that the binding energy of Picrasidine Y and the inflammatory factors VEGFA is the highest. This study predicted the role of multiple active compounds in the alkaloids of Picrasma in the inflammatory response, and provided a theoretical basis for the anti-inflammatory mechanism of Picrasma

Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents / A Rubiadina exerce um efeito anti-inflamatório agudo e crônico em roedores

Rubiadin is identified as a bioactive anthraquinone that exists in some quinone rich plants. The current research was carried out to evaluate the potential anti-inflammatory impact of Rubiadin in acute and chronic inflammation test models in rodents. The anti-inflammatory activity of Rubiadin was examined in cotton pellet-induced granuloma and carrageenan-induced edema as chronic and acute inflammation models in rats. TNF-α level and histopathological changes were assessed using sampled foot tissue of rat in the acute model. Also, the IL-1β level was assessed in the chronic model. One-way ANOVA (post hoc Tukey’s) analysis was used for comparing the groups. Rubiadin (0.5 mg/kg, i.p.) induced a significant reduction in TNF α level and the paw edema compared to the control group in carrageenan test. Also, it was observed that the anti-inflammatory activity of Rubiadin (0.5 mg/kg, i.p.) is comparable to mefenamic acid (30 mg/kg, i.p.) as the standard drug. Rubiadin was effective in granuloma induced by cotton pellet concerning the granuloma and transudate formation amount. Rubiadin's anti-inflammatory effects were associated with a significant IL-1β decrease in this model. The results suggest that Rubiadin as a natural compound can possess significant peripheral anti-inflammatory impacts.

A rubiadina é identificada como uma antraquinona bioativa que existe em algumas plantas ricas em quinonas. A presente pesquisa foi realizada para avaliar o potencial impacto anti-inflamatório da rubiadina em modelos de teste de inflamação aguda e crônica em roedores. A atividade anti-inflamatória da rubiadina foi examinada em granuloma induzido por pellet de algodão e edema induzido por carragenina como modelos de inflamação crônica e aguda em ratos. O nível de TNF-α e as alterações histopatológicas foram avaliados usando amostra de tecido do pé de rato no modelo agudo. Além disso, o nível de IL-1β foi avaliado no modelo crônico. A análise ANOVA de uma via (post hoc de Tukey) foi usada para comparar os grupos. A rubiadina (0,5 mg / kg, i.p.) induziu uma redução significativa no nível de TNF α e no edema da pata em comparação com o grupo de controle no teste de carragenina. Além disso, foi observado que a atividade anti-inflamatória da rubiadina (0,5 mg / kg, i.p.) é comparável ao ácido mefenâmico (30 mg/kg, i.p.) como o fármaco padrão. A rubiadina foi eficaz no granuloma induzido por pellet de algodão no que diz respeito à quantidade de granuloma e formação de transudato. Os efeitos anti-inflamatórios da rubiadina foram associados a uma redução significativa de IL-1β nesse modelo. Os resultados sugerem que a rubiadina como um composto natural pode ter impactos anti-inflamatórios periféricos significativos.

Evaluation of vitamin D and inflammatory markers in elderly

Abstract Vitamin D is an immune modulator, in addition to being interrelated with calcium homeostasis and bone metabolism. Recent studies have associated vitamin D with inflammatory processes. C-reactive protein (CRP), platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) have been used to determine inflammation. There is no consensus on the use of these markers to determine an association between inflammation and vitamin D levels. The objective of this study was to evaluate the association between inflammatory markers and vitamin D in the elderly. A cross-sectional, descriptive study was performed based on the analysis of vitamin D, CRP (quantitative determination of C-Reactive Protein by the ultra-sensitive method) and blood count of institutionalized elderly. In this study, 64% showed vitamin D deficiency, with mean value of 22 ng/mL. In the vitamin D deficient group, the mean values found were: CRP 4.5 mg/L; NLR 2.35 and PLR 119. In the group without vitamin D deficiency the mean values were: CRP 4 mg/L; NLR 1.87 and PLR 111 without statistical difference between the values of the analyzed parameters. The results point to a predominant profile of vitamin D deficiency in the evaluated individuals. No association was found between vitamin D values and the inflammatory markers analyzed.

Antinociceptive and anti-inflammatory activities of Hymenaea martiana Hayne (Fabaceae) in mice / Atividade antinociceptiva e anti inflamatória de Hymenaea martiana Hayne (Fabaceae) em camundongos

Hymenaea martiana is a species popularly known in Northeastern Brazil as "jatobá" and used in folk medicine to treat pain and inflammation. The aim of this work was to evaluate the antinociceptive and anti-inflammatory activity of H. martiana. In the present study, we carried out an investigation about the effects of the crude ethanolic extract (Hm-EtOH) and the ethyl acetate fraction (Hm-AcOEt) in models of nociception and inflammation in mice. Chemical (acetic acid-induced writhing and formalin) and thermal stimuli (hot plate) were used for the evaluation of antinociceptive activity, while for the anti-inflammatory profile paw edema induced by carrageenan was used, along with leukocyte migration to the peritoneal cavity. The presence of the flavonoid astilbin in the samples was characterized through HPLC-DAD-MS analysis. Hm-EtOH and Hm-AcOEt (100, 200 and 400 mg.kg-¹, i.p.) significantly reduced the number of abdominal contortions and decreased the paw licking time in the formalin test. In the hot plate, the extract increased the latency time of animals. Hm-EtOH and Hm-AcOEt inhibited significantly the increase in the edema after the administration of carrageenan. Hm-EtOH and Hm-AcOEt inhibited leukocyte migration in the peritonitis test. HPLC-DAD-MS analysis of Hm-EtOH and Hm-AcOEt revealed the presence of the flavonoid astilbin in the samples. According to the results of this study, both Hm-EtOH and Hm-AcOEt have antinociceptive and anti-inflammatory activities, which could be related with the presence of flavonoid in the extracts. The results reinforce the popular use of this plant.

Hymenaea martiana é uma espécie popularmente conhecida no Nordeste do Brasil como “jatobᔠe usada na medicina popular para tratar a dor e a inflamação. O objetivo deste trabalho foi avaliar a atividade antinociceptiva e anti inflamatória de H. martiana. No presente estudo, foram avaliados os efeitos do extrato etanólico bruto (Hm-EtOH) e da fração acetato de etila (Hm-AcOEt) em modelos de nocicepção e inflamação em camundongos. Foram utilizados estímulos químicos (contorções abdominais induzidas por ácido acético e teste da formalina) e estímulo térmico (teste da placa quente) para avaliação da atividade antinociceptiva, enquanto no perfil anti-inflamatório foi utilizado o teste do edema de pata induzido por carragenina e migração de leucócitos para a cavidade peritoneal. A presença do flavonoide astilbina nas amostras foi caracterizada através de análise por CLAE-DAD-EM. Hm-EtOH e o Hm-AcOEt (100, 200 e 400 mg.kg-¹, i.p.) reduziram significativamente o número de contorções abdominais e diminuíram o tempo de lambida da pata no teste da formalina. No teste da placa quente, houve aumento do tempo de latência dos animais. Hm-EtOH e Hm-AcOEt inibiram significativamente o aumento do edema após a administração de carragenina, bem como inibiram a migração de leucócitos no teste de peritonite. A análise por CLAE-DAD-EM de Hm-EtOH e Hm-AcOEt revelou a presença do flavonoide astilbina nas amostras. De acordo com os resultados deste estudo, tanto Hm-EtOH quanto o Hm-AcOEt possuem atividades antinociceptiva e anti-inflamatória, o que pode estar relacionado à presença do flavonoide. Os resultados reforçam o uso popular desta planta.

Anti-inflammatory activities of arthropod peptides: a systematic review

Peptides obtained from different animal species have gained importance recently due to research that aims to develop biopharmaceuticals with therapeutic potential. In this sense, arthropod venoms have drawn attention, not only because of their toxicity but mainly for the search for molecules with various bioactivities, including anti-inflammatory activity. The purpose of the present study is to gather data available in the literature on new peptides derived from arthropod species with anti-inflammatory potential. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies on peptides from arthropods that display anti-inflammatory activity were retrieved from PubMed, Scopus, Web of Science, and Google Scholar databases. The bibliographic research started in 2020 and searched papers without a limit on the publication date. The articles were analyzed using a search string containing the following terms: "Peptides" and "Anti-inflammatory", in combinations such as "Ant", "Bee", "Wasp", "Crab", "Shrimp", "Scorpion", "Spider", "Tick" and "Centipedes". Besides, a search was carried out in the databases with the terms: "Peptides", "Antitumor", or "Anticancer", and "Arthropods". Articles that met the inclusion and exclusion criteria totalized 171, and these served for data extraction. Additionally, the present review included anti-inflammatory peptides with anticancer properties. Peptides with confirmed anti-inflammatory activity were from insects (ants, bees, and wasps), crustaceans (shrimp and crabs), arachnids (scorpions, spiders, and ticks), and centipedes. These arthropod peptides act mainly by decreasing pro-inflammatory cytokines as analyzed in vitro and in vivo. Some showed significant antineoplastic activity, working in essential cellular pathways against malignant neoplasms.(AU)

Antilipoperoxidative and anti-inflammatory efficacy of multifunctional sunscreens containing ferulic acid

Unprotected chronic exposure to ultraviolet radiation generates many harmful effects to human skin and UV filters are essential to health, however, traditional sunscreens do not provide enough protection against cutaneous oxidative stress, a process amplified by UV radiation. Therefore, is been proposed the development of multifunctional photoprotective formulations, acting in the absorption/reflection of UV radiation and assisting in cutaneous homeostasis. In the present study, ferulic acid is used in conjunction with two sunscreens, bemotrizinol and ethylhexyl triazone, for the determination of biosafety and efficacy methods, using techniques that better elucidate the effects of ferulic acid. Skin permeation assays were performed by applying a formulation containing the three substances in the stratum corneum of volunteers, which were removed by the tape stripping method (ex vivo) with follow quantification by high performance liquid chromatography (HPLC). The test was able to evaluate the penetration depth of the substances, characterizing them. In addition, the simultaneous quantification of the three substances was performed by a single and fast method, facilitating their analysis and improving the technique. Also, TBARS (thiobarbituric acid reactive substances) assays were performed in stratum corneum removed by tape stripping (ex vivo), evaluating the potential of cutaneous lipid peroxidation, with or without ferulic acid. To date, it is the first time that TBARS method is used to characterize the stratum corneum (ex vivo) and quantified by HPLC. The protocol developed may aid in the efficacy of antioxidant agents in studies aimed at elucidating the level of lipid peroxidation caused by drugs and cosmetics, and even in carrying out baseline studies characterizing different ethnicities and genders. As last, an anti-inflammatory in vivo assay with Laser Doppler flowmetry equipment was used to compare the sunscreen formulation with or without ferulic acid. Data indicated that the antioxidant reduced the angular coefficient of the perfusion units, mitigating the inflammatory effects. Furthermore, a significant difference was found between the genders, suggesting a more pronounced inflammatory reaction in women. Ferulic acid proved to be a valuable resource, besides being safe and raise the SPF of sunscreens, it also mitigates the effects of inflammation

A exposição crônica desprotegida à radiação ultravioleta (UV) contribui para o desenvolvimento de câncer de pele e os filtros solares são relevantes para evitar tais efeitos prejudiciais, porém, os protetores solares tradicionais não geram proteção suficiente contra o estresse oxidativo cutâneo. Logo, espera-se o desenvolvimento de formulações fotoprotetoras multifuncionais, atuando não somente na absorção e/ou reflexão da radiação UV, mas, também, auxiliando na homeostase cutânea, com presença de agentes antioxidantes. No presente estudo foi utilizado o ácido ferúlico conjuntamente com dois filtros solares, o bemotrizinol e a triazona de octila, para determinação de métodos de segurança e eficácia, utilizando técnicas que melhor elucidem e comprovem os efeitos do ácido ferúlico. Foram realizados ensaios de permeação cutânea pela aplicação tópica de formulação contendo as três substâncias em voluntários, sendo o estrato córneo retirado pelo método de tape stripping (ex vivo) com subsequente quantificação por cromatografia líquida de alta eficiência (CLAE). O ensaio pôde avaliar a profundidade de penetração das substâncias, caracterizando-as. Ademais, a quantificação simultânea das três substâncias foi efetuada por método único e rápido, facilitando análise com aprimoramento da técnica. Em adição, foi realizado ensaios de TBARS (substâncias reativas ao ácido tiobarbitúrico) em estrato córneo removido por tape stripping (ex vivo), para avaliar o potencial de peroxidação lipídica cutânea, contendo ou não o ácido ferúlico. Até o presente momento, é a primeira vez que o método TBARS é utilizado para caracterização do estrato córneo (ex vivo) e quantificada por CLAE. O protocolo desenvolvido pode auxiliar na eficácia de agentes antioxidantes, em estudos que visam elucidar o nível de peroxidação lipídica causada por medicamentos e cosméticos e, até mesmo, na realização de estudos de base, caracterizando etnias e gêneros. Ademais, um ensaio anti-inflamatório in vivo com equipamento de fluxometria Laser Doppler foi utilizado para comparar a formulação fotoprotetora com ou sem ácido ferúlico. Os dados indicaram que o antioxidante reduziu o coeficiente angular das unidades de perfusão, mitigando os efeitos inflamatórios. Ainda, foi identificada diferença entre os gêneros, sugerindo reação inflamatória mais pronunciada em mulheres. O ácido ferúlico provou ser um recurso valioso, além de ser seguro e elevar o FPS dos fotoprotetores, também atenuando os efeitos da inflamação

Guideline values and human risk assessment for the presence of anti-inflammatory drugs remaining in drinking water after lab scale treatment

This study aimed to determine whether the anti-inflammatory drugs that are most commonly consumed in Brazil, including diclofenac, ketoprofen, naproxen, indomethacin, ibuprofen and acetaminophen, are present in drinking water and to derive guideline values to characterize the human risk. These pharmaceuticals were quantified in surface waters by LC-MS/MS with solid phase extraction, both before and after conventional treatment on a laboratory scale, using a jar test assay. The methods used to quantify these drugs showed good results: the chromatographic analysis obtained correlation coefficients between 0.9952 and 0.9991, with limits of quantification of 0.5 ng.mL-1 - 50 ng.mL-1 and precision standard deviations (0.08 - 2.08). Only ketoprofen and ibuprofen were not completely removed through the jar test. Environmental samples were collected and handled by the same method; the values |for ketoprofen and ibuprofen after treatment were 18.67 - 19.65 ng.L-1 (±17%) and 166.70 - 244.73 ng.L-1 (±14%), respectively. Human risk was assessed by comparing the guideline values for each compound to the concentrations obtained in the environmental samples, considering the toxicological backgrounds, following WHO (2011) method. The results suggest that the concentrations of ketoprofen and ibuprofen found in drinking water do not pose a risk to human health, even with chronic consumption

A pH-responsive drug delivery matrix from an interpolyelectrolyte complex: preparation and pharmacotechnical properties

ABSTRACT Interpolyelectrolyte complexes, which constitute a type of polymeric material obtained through the self-assembly of oppositely charged polymers, exhibit interesting properties for use in the design of smart matrices for drug delivery. In the present study, a stoichiometric interpolyelectrolyte complex (SIPEC) composed of Eudragit E® and Eudragit® L100 was obtained at pH 6.0 and characterized and evaluated as a hydrophilic matrix for dexibuprofen. The formation of a SIPEC was monitored by ζ-potential measurements and characterized using infrared spectroscopy, thermal analysis, and scanning electron microscopy. The results indicated that a SIPEC obtained under these conditions can be used as a matrix for controlling the release of dexibuprofen and exhibit a pH-triggered release

Lentinula edodes based GIS mapping, biometabolites and antiinflamatory activity of wild edible mushrooms from tropical 'sacred grove' forests of Meghalaya, India / Mapas basados en GIS deLentinula edodes, biometabolitos y actividad antiinflamatoria de los hongos silvestres comestibles de los bosques tropicales "bosque sagrado" de Meghalaya, India

AbstractThe biodiversity rich state of Meghalaya, India located in the realms of mega-biodiversity hotspots, is home to numerous species of wild edible macrofungi that are used extensively by the mycophillic ethnic population, as a part of their traditional cuisine and medicine systems. However, habitat loss, due to deforestation and climate change, is destroying the natural population of these mushrooms, depleting their availability to the local communities. In the present investigation, a GIS guided habitat search, using Lentinula edodes as a representative species, was used in mapping the habitats of wild edible macrofungi of the study region. Sampling of around 4 000 specimens per distinct morphological type available in the traditional markets and "sacred grove" forests indicated presence of ten common genera, belonging to nine different families of wild edible mushrooms. Nutritional profiling of the representative species Lentinula edodes was carried out by evaluation of its moisture, total fat, crude protein and carbohydrates contents by standard methods. Similarly, bioactive components determination was performed by estimation of total phenols, flavonoids, ascorbic acid, β-carotene and lycopenes. Bioactivity of the mushrooms extracts was studied using the DPPH radical scavenging and Human Red Blood Cell (HRBC) membrane stabilization assays. The present investigation successfully attempted to explore remote sensing technologies and GIS (Geographic Information System) based system to predict the natural habitats of wild edible mushrooms of Meghalaya, India which we believe will lead to the generation of a mushroom specific non-wood forest resource mapping system in the near future. Results of nutritional profiling and biological activity studies on the representative species of wild edible mushrooms from the studied region revealed that it is a rich source of essential nutrients and antioxidants.

ResumenLa rica biodiversidad del estado de Meghalaya, India situado en los reinos de los hotspots mega-biodiversidad es el hogar de numerosas especies de macro hongos silvestres comestibles que se utilizan ampliamente por la población étnica micofílica como parte de su alimentación y medicina tradicional. Sin embargo, la pérdida de hábitat debido a la deforestación y el cambio climático está destruyendo la población natural de estos hongos, que agotan su disponibilidad para las poblaciones locales. En la presente investigación, se utilizó el SIG para la búsqueda guiada de hábitat usando Lentinula edodes como especie representativa en la cartografía de los hábitats de macrohongos silvestres comestibles de la región de estudio. Alrededor de cuatro mil ejemplares de distinto tipo morfológico fueron muestreados según su disponibilidad en los mercados tradicionales y los "sacred grove" (bosques sagrados) lo que indicó la presencia de diez géneros comunes pertenecientes a nueve familias de setas silvestres comestibles. Perfiles nutricionales de las especies representativas Lentinula edodes se llevaron a cabo mediante la evaluación de su humedad, grasa total, proteína cruda y contenido de carbohidratos. Del mismo modo, la determinación de componentes bioactivos se realizó por estimación de fenoles totales, flavonoides, ácido ascórbico, β-caroteno y licopeno. La bioactividad de los extractos de setas se estudió mediante la captación de radicales DPPH y el ensayo de estabilización de la membrana de glóbulos rojos de la sangre humana (hRBC). Los resultados de estudios de perfiles nutricionales y actividad biológica en hongos comestibles revelan que es una fuente rica en nutrientes esenciales y antioxidantes. La presente investigación ha intentado con éxito explorar las tecnologías de teledetección y SIG (Sistema de Información Geográfica) para predecir el hábitat natural de los hongos silvestres comestibles de Meghalaya, India que creemos dará lugar a la generación de un mapeo de los recursos forestales no madereros, específicamente de hongos, en el futuro cercano.

C–reactive protein estimation: A quantitative analysis for three nonsteroidal anti‑inflammatory drugs: A randomized control trial.

Context: C‑reactive protein (CRP) estimation for quantitative analysis to assess anti‑inflammatory action of nonsteroidal anti‑inflammatory drugs (NSAIDs) after surgery in maxillofacial surgery. Aims: This study was to evaluate the efficacy of CRP as a quantitative analysis for objective assessment of efficacy of three NSAIDs in postoperative inflammation and pain control. Settings and Design: The parallel study group design of randomization was done. Totally 60 patients were divided into three groups. CRP was evaluated at baseline and postoperatively (immediate and 72 h) after surgical removal of impacted lower third molar. The respective group received the drugs by random coding postoperatively. Subjects and Methods: The assessment of pain control and inflammation using NSAIDs postoperatively after surgical removal of impacted lower third molar was qualitatively and quantitatively assessed with CRP levels. The blood sample of the patient was assessed immediate postoperatively and after 72 h. The visual analog scale (VAS) was used for assessment of pain and its correlation with CRP levels. Statistical Analysis: Comparison of difference in levels of CRP levels had P < 0.05 with immediate postoperative and baseline levels. The duration of surgery with association of CRP levels P = 0.425 which was nonsignificant. The pain score was increased with mefenamic acid (P = 0.003), which was significant on VAS. Results: Diclofenac had the best anti‑inflammatory action. There was a significant increase in CRP levels in immediate postoperative values and 72 h. CRP test proved to be a useful indicator as a quantitative assessment tool for monitoring postsurgical inflammation and therapeutic effects of various anti‑inflammatory drugs. Conclusions: CRP test is a useful indicator for quantitative assessment for comparative evaluation of NSAIDs.

Anti-inflammatory components of the Vietnamese starfish Protoreaster nodosus

BACKGROUND: In the present study, we examined the inhibitory effects of a methanolic extract, dichloromethane fraction, water layer, and polyhydroxylated sterols (1-4) isolated from the Vietnamese starfish Protoreaster nodosus on pro-inflammatory cytokine (IL-12 p40, IL-6, and TNF-α) production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) using enzyme-linked immunosorbent assays (ELISA). RESULTS: The methanolic extract and dichloromethane fraction exerted potent inhibitory effects on the production of all three pro-inflammatory cytokines, with IC50 values ranging from 0.60 ± 0.01 to 26.19 ± 0.64 µg/mL. Four highly pure steroid derivatives (1-4) were isolated from the dichloromethane fraction and water layer of P. nodosus. Potent inhibitory activities were also observed for (25S)5α-cholestane-3ß,4ß,6α,7α,8ß,15α,16ß,26-octol (3) on the production of IL-12 p40 and IL-6 (IC50s = 3.11 ± 0.08 and 1.35 ± 0.03 µM), and for (25S) 5α-cholestane-3ß,6α,8ß,15α,16ß,26-hexol (1) and (25S)5α-cholestane-3ß,6α,7α,8ß,15α,16ß,26-heptol (2) on the production of IL-12 p40 (IC50s = 0.01 ± 0.00 and and 1.02 ± 0.01 µM). Moreover, nodososide (4) exhibited moderate inhibitory effects on IL-12 p40 and IL-6 production. CONCLUSION: This is the first report of the anti-inflammatory activity from the starfish P. nodosus. The main finding of this study is the identification oxygenated steroid derivatives from P. nodosus with potent anti-inflammatory activities that may be developed as therapeutic agents for inflammatory diseases.

Use of Curcuma longa in cosmetics: extraction of curcuminoid pigments, development of formulations, and in vitro skin permeation studies

Curcuma longa is a ginger family aromatic herb (Zingiberaceae) whose rhizomes contain curcuminoid pigments, including curcumin, a compound known for its anti-inflammatory effects. The objective of this study was to obtain curcuminoid-rich extracts, develop topical formulations thereof, and assess the stability and skin permeation of these formulations. Curcuma longa extracts were obtained and used to develop formulations. Skin permeation studies were conducted in a modified Franz diffusion cell system, and skin retention of curcuminoid pigments was quantified in pig ear membrane. Prepared urea-containing gel-cream formulations were unstable, whereas all others had satisfactory stability and pseudoplastic rheological behavior. The amount of curcuminoid pigments recovered from the receptor solution was negligible. The skin concentration of curcuminoid pigments retained was positive (>20 µg/g of skin, mostly in the stratum corneum), considering the low skin permeability of curcumin. We conclude that development of topical formulations containing curcumin or Curcuma longa extract is feasible, as long as adjuvants are added to improve preservation and durability. The formulations developed in this study enabled penetration of curcumin limited to the superficial layers of the skin and then possibly without a risk of systemic action, thus permitting local use as a topical anti-inflammatory.

Curcuma longa é uma erva aromática, pertencente à família Zingiberaceae e seus rizomas contêm pigmentos curcuminoides, dentre eles a curcumina, conhecida por seu efeito anti-inflamatório. O objetivo deste trabalho foi obter extratos ricos nestes pigmentos, desenvolver e avaliar a estabilidade de formulações tópicas e realizar o estudo da penetração cutânea. Extratos de Curcuma longa foram obtidos e utilizados no desenvolvimento de formulações. A penetração e retenção cutâneas de pigmentos curcuminoides foi avaliada em pele de orelha de porco, utilizando célula de difusão de Franz modificada. As formulações de gel creme preparadas que continham ureia foram instáveis e as demais apresentaram estabilidade satisfatória e comportamento reológico pseudoplástico. A quantidade de pigmentos curcuminoides encontrada na solução receptora foi insignificante, enquanto que a quantidade retida na pele foi superior a 20 µg/g de pele. Concluiu-se como possível o desenvolvimento de formulações tópicas contendo curcumina ou extrato de Curcuma longa, conciliando a adição de adjuvantes para a preservação e maior durabilidade da mesma. As formulações promoveram a penetração da curcumina limitada às camadas superiores da pele, possivelmente sem o risco de ocorrência de ação sistêmica sendo possível a sua utilização para ação local com atividade anti-inflamatória.

Tratamento com anti-inflamatórios sobre a quantidade e qualidade dos complexos Cumulus oophorus aspirados dos ovários de novilhas / Treatment with anti-inflammatory on the quantity and quality of the Cumulus oophorus complexes aspirated from the ovaries of heifers

A produção de embrião in vitro (PIV) associada à aspiração folicular transvaginal guiada O número médio de folículos a serem aspirados (imagem ultrassom) foi semelhante em todos os tratamentos (p>0,05). O Grupo III apresentou menor média de COC’s viáveis (p<0,05), enquanto o grupo Controle e o tratado com flunixin meglumine apresentaram média de COC’s viáveis semelhante (p>0,05). O número médio de COC’s aspirados no Grupo Controle foi 19,52 ± 11,00 COC’s e o de COC’s viáveis de 14,09 ± 8,53 por sessão de aspiração folicular. O número médio de ovócitos Grau I e II foi semelhante entre os grupos experimentais (p>0,05). No entanto, o número médio de ovócitos Grau III foi menor nos animais tratados com meloxicam (p<0,05). O número de ovócitos sem cumulus foi semelhante entre os grupos experimentais (p>0,05), enquanto o número de ovócitos atrésicos apresentou diferença somente entre os grupos tratados com anti-inflamatório (p<0,05), onde os animais tratados com meloxicam, apresentaram menor número médio de ovócitos atrésicos.

The production of bovine embryo in vitro (PIV) associated to the ultrasound-guided transvaginal folicularaspiration (OPU - Ovum pick-up) provided an increment in the reproduction productivity of cows, being of great importancefor the fast multiplication of these animals. However, it can cause morphologic and functional alterations in the ovaries. Thisstudy aims to evaluate the anti-inflammatory effects on the quantity and quality of cumulus oophorus complexes (COC’s)aspirated from the ovaries of crossbred heifers treated with anti-inflammatory. In order to do so, 18 heifers were divided inthree treatment groups, being Group I Control, II treated with Flunixin Meglumine (1.1 mg/Kg - Banamine®) and III treatedwith Meloxican (0,5 mg/kg - Maxicam®). The animals were submitted to ten OPU’s, being the collected oocytes quantifiedand evaluated. The average number of follicles to be aspirated was similar in all the treatments (p> 0.05). Group III showeda smaller average number of viable COC’s (p<0.05), whereas the Control group and the one treated with flunixin meglumineshowed a similar average number of viable COC’s (p>0.05). In the Control Group the average number of aspirated COC’swas 19.52 ± 11.00 COC’s and the average number of viable COC’s was 14.09 ±8.53 per folicular aspiration session. Theaverage number of oocytes of Degree I and II was similar among the experimental groups (p> 0.05). However, the averagenumber of oocytes of Degree III was smaller in the animals treated with meloxicam (p<0.05). The number of oocytes withoutcumulus was similar among the groups (p> 0.05), whereas the number of atresic oocytes showed difference among the groupstreated with anti-inflammatory, where that one treated with meloxicam showed a smaller average number of atresic oocytes.

Atividades antioxidante, antinociceptiva e anti-inflamatória das folhas de Mucuna pruriens (L. ) DC / Antioxidant, antinociceptive and anti-inflammatory activity of Mucuna pruriens (L. ) DC. leaves

A espécie Mucuna pruriens (L.) DC. (Fabaceae) é popularmente conhecida no Brasil como "café berão" e "pó de mico". Suas sementes são bastante estudadas sendo empregadas na medicina popular para o tratamento de desordens nervosas e do aparelho reprodutor, porém poucas informações sobre a composição química e atividade farmacológica das folhas dessa espécie são descritas na literatura. Assim, os objetivos desse estudo foram: a determinação do perfil fitoquímico, a avaliação da atividade antioxidante in vitro, e a avaliação das atividades anti-inflamatória e antinociceptiva in vivo do extrato metanólico das folhas de M. pruriens nas concentrações de 100 e 300 mg/kg. O estudo fitoquímico foi realizado por meio da pesquisa qualitativa dos constituintes químicos e determinação quantitativa do teor de fenóis totais e flavonoides. O potencial antioxidante foi avaliado pelos métodos do DPPH e poder de redução. As atividades anti-inflamatória e antinociceptiva foram a ante foi promissor, com CI50 de 13,2∝g/mL pelo método do DPPH, e CE50 de 47,9∝g/mL pelo método que avalia o poder de redução. Em relação à atividade anti-inflamatória, o extrato foi capaz de inibir o edema de orelha em 63% (100mg/kg) e 28% (300mg/kg). Quanto à atividade antinociceptiva, houve redução do número de contorções abdominais de 64% (100 mg/kg) e 69% (300 mg/kg). Estes resultados indicam que M. pruriens apresenta um potencial farmacológico promissor e reforçam o conceito de que a pesquisa de plantas com usos etnofarmacológicos pode revelar um número substancial de respostas em ensaios in vitro e in vivo.

The species Mucuna pruriens (L.) DC. (Fabaceae) is popularly known in Brazil as "café berão" and "pó de mico". Its seeds have been widely studied and used in folk medicine for the treatment of nervous and reproductive system disorders; however, few studies are related to the chemical composition and pharmacological activity of its leaves. Therefore, the aims of this study were: investigation of the phytochemical profile, in vitro assessment of the antioxidant activity, and in vivo evaluation of the anti-inflammatory and antinociceptive activities of methanol extract of M. pruriens leaves at the concentrations of 100 and 300mg/kg. The phytochemical study was performed by means of qualitative identification of chemical constituents and quantitative determination of total phenols and flavonoids. The antioxidant potential was assayed by DPPH and reducing power methods. Anti-inflammatory and antinociceptive activities were evaluated by croton oil-induced ear edema and acetic acid-induced writhing tests, respectively. Alkaloids, coumarins, flavonoids, triterpenes and saponins were identified in the extract. Total phenol and flavonoid levels were 112 and 18.3mg/g extract, respectively. The antioxidant potential was promising, with IC50 of 13.2∝g/mL by DPPH assay and EC50 of 47.9∝g/mL by the method that evaluates the reducing power. Regarding the anti-inflammatory activity, the extract was capable of inhibiting by 63% (100mg/kg) and 28% (300mg / kg) the ear edema. As to the antinociceptive activity, there was a reduction in the number of writhings by 64% (100mg/kg) and 69% (300mg/kg). Results indicate that M. pruriens presents a promising pharmacological potential and reinforce the concept that the investigation of ethnopharmacologically used plants may reveal a substantial number of positive responses in in vitro and in vivo assays.

Avaliação da atividade antiedematogênica, antimicrobiana e mutagênica das sementes de Amburana cearensis (A. C. Smith) (Imburana-de-cheiro) / Assessment of the antiedematogenic, antimicrobial and mutagenic activity of Amburana cearensis seeds (A.C. Smith) (Imburana-de-cheiro)

Foram avaliados os efeitos antiinflamatório, antibacteriano e mutagênico do extrato aquoso das sementes de Amburana cearensis. A atividade antiinflamatória foi avaliada em modelo de edema de pata induzido por carragenina, utilizando o extrato em concentrações de 10 % e 20 % nos grupos experimentais; AAS 10 mg/kg (v.o) no grupo padrão e água destilada no grupo controle. A atividade antimicrobiana foi determinada através do método de diluição em Agar, utilizando concentrações de extrato de 10 %, 7,5 %, 5 %, 2,5 % e 1 % em cepas de Sthaphylococcus aureus ATCC 27853, Escherichia coli ATCC 25922 e Pseudomonas aeruginosas ATCC 25923) e a atividade mutagênica foi determinada pelo teste de Allium cepa, utilizando extrato em concentrações de 0,02 mg/mL, 0,1 mg/mL e 0,5 mg/mL. O extrato aquoso das sementes de Amburana cearensis nas concentrações de 10 % e 20 % apresentou efeito antiedematogênico, estatisticamente significativo a partir de duas horas após administração do flogógeno, e tal efeito persistiu até 24 horas após a indução da resposta inflamatória. Quanto à atividade antibacteriana, o extrato não apresentou ação contra as cepas bacterianas de Sthaphylococcus aureus, Escherichia coli e Pseudomonas aeruginosas nas concentrações testadas. A análise dos resultados do teste de Allium cepa evidenciou ação tóxica (em concentração de 0,5 mg/mL) e mutagênica (micronúcleo 0,1 mg/mL e aberrações cromossômicas 0,1 mg/mL e 0,5 mg/mL) do extrato de Amburana cearensis em células meristemáticas de Allium cepa. Tais resultados sugerem potencial aplicação terapêutica no tratamento da inflamação. Contudo, também demonstram a necessidade de estudar para comprovar a segurança na utilização dessa espécie.

The anti-inflammatory, antibacterial and mutagenic effects of the aqueous extract of Amburana cearensis seeds were evaluated. The anti-inflammatory activity was evaluated by a paw edema model induced by carrageenan, using the extract at 10 % and 20 % concentrations in the experimental groups: AAS 10 mg/kg (orally administrated) in the standard group and distilled water in the control group. The antimicrobial activity was determined by the agar dilution method, using extract concentrations of 10 %, 7.5 %, 5 %, 2.5 % and 1% in strains of Staphylococcus aureus ATCC 27853, Escherichia coli ATCC 25922 and Pseudomonas aeruginosas ATCC 25923), and the mutagenic activity was determined by the Allium cepa test using extract concentrations of 0,02 mg/mL, 0,1 mg/mL and 0,5 mg/mL. The aqueous extract of Amburana cearensis seeds at 10 % and 20 % concentrations had an statistically significant antiedematogenic effect two hours after administering the flogogen, and this effect persisted for up to 24 hours after inducing the inflammatory response. Regarding the antibacterial activity, the extract showed no action against the bacterial strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosas at the concentrations tested. The results of the Allium cepa test showed the toxic (at a concentration of 0,5 mg/mL) and mutagenicity (0.1 mg/mL micronucleus and 0.1 mg/mL and 0.5 mg/mL chromosomal aberrations) actions of the Amburana cearensis extract on meristematic cells of Allium cepa. These results suggest potential therapeutic applications to treat inflammations. However, they also show the need for further studies to demonstrate the safe use of this species.

Produtos naturais ativadores de PPAR e marcadores associados ao processo inflamatório na Síndrome Metabólica / The inflammatory process in the metabolic syndrome: PPAR activators of natural products and markers associated with metabolic disorders

O processo inflamatório é o elo entre a síndrome metabólica e as doenças cardiovasculares. Para verificar a presença e o grau da inflamação, vários biomarcadores têm sido propostos e investigados. Este trabalho tem como objetivo revisar as recentes pesquisas que associam alguns marcadores expressos no tecido adiposo, enfatizando, dentre eles, a adiponectina, a resistina, a leptina e o transportador de glicose GLUT-4 na síndrome metabólica, a relação da inflamação decorrente desse conjunto de desordens metabólicas sob os receptores proliferadores peroxissomais (PPARs), bem como o efeito de diferentes extratos vegetais e produtos naturais bioativos na ativação desses receptores.

The inflammatory process is the link between metabolic syndrome and cardiovascular diseases. To verify the presence and degree of inflammation, several biomarkers have been proposed and different receptors have been investigated. This study aims to review recent researches involving some markers expressed in the adipose tissue, emphasizing, among them, adiponectin, resistin, leptin and glucose transporter GLUT-4 in the metabolic syndrome, the relationship of inflammation arising from this set of metabolic disorders on the peroxisome proliferator receptors (PPARs) and the effect of different bioactive compounds in the activation of these receptors.

Dendrimers as anti-inflammatory agents

Dendrimers constitute an intriguing class of macromolecules which find applications in a variety of areas including biology. These hyperbranched macromolecules with tailored backbone and surface groups have been extensively investigated as nanocarriers for gene and drug delivery, by molecular encapsulation or covalent conjugation. Dendrimers have provided an excellent platform to develop multivalent and multifunctional nanoconjugates incorporating a variety of functional groups including drugs which are known to be anti-inflammatory agents. Recently, dendrimers have been shown to possess anti-inflammatory properties themselves. This unexpected and intriguing discovery has provided an additional impetus in designing novel active pharmaceutical agents. In this review, we highlight some of the recent developments in the field of dendrimers as nanoscale anti-inflammatory agents.

Dendrímeros constituem uma classe intrigante de macromoléculas que apresentam aplicações em diversas áreas incluindo biologia. Essas macromoléculas extremamente ramificadas com esqueleto planejado e grupos de superfície foram extensivamente investigadas como nanotransportadores de genes e de fármacos, por encapsulamento molecular ou conjugação covalente. Dendrímeros têm proporcionado uma plataforma excelente de desenvolvimento nanoconjugados multivalentes e multifuncionais incorporando uma variedade de grupos funcionais, incluindo fármacos que são conhecidos por atuarem agentes antiinflamatórios. Recentemente, os dendrímeros mostraram propriedades antiinflamatórias. Esta inesperada e intrigante descoberta tem proporcionado um impulso adicional no planejamento de novos agente farmacêuticos ativos. Nesta revisão, nós destacamos alguns dos desenvolvimentos recentes no campo dos dendrímeros como agentes antiinflamatórios em nanoescala.

Analgesic and anti-inflammatory activities of several 4-substituted-6-(3'-nitrophenyl)pyridazin-(2H)-3-one derivatives

Several 6-aryl-4-substituted benzylidene/furfurylidene pyridazin(2H)-3-one derivatives (4a-f) were synthesized and evaluated as analgesic and anti-inflammatory agents in mice and rats, respectively. All compounds were tested by using Eddy's hot plate and the carrageenan-induced hind paw oedema method for the evaluation of analgesic and anti-inflammatory activities, respectively. Results showed that compounds 4f, 4b, 4d, and 4e exhibited higher analgesic and anti-inflammatory activities than other remaining compounds. All title compounds (4a-f) were characterized by IR, NMR and Mass spectroscopy.

Diversos derivados benzilideno/furfurilideno piridazin(2H)-3-ona 6-aril-4-substituídos (4a-f) foram sintetizados e avaliados como analgésicos e anti-inflamatórios em camundongos e ratos, respectivamente. Todos os compostos foram testados utilizando-se o método de placa quente de Eddy e o de edema de pata induzido por carragenana para a avaliação das atividades analgésica e anti-inflamatória, respectivamente. Os resultados mostraram que os compostos 4f, 4b, 4d e 4e exibiram atividade analgésica e anti-inflamatória mais alta do que os compostos restantes. Todos os compostos (4a-f) foram caracterizados por IV, RMN e espectrometria de massas.

Funcionalismo hepático en ratas wistar tratadas con dosis terapéuticas de nimesulide / Liver function in wistar rats treated with therapeutic doses of nimesulide

Introducción: El nimesulide es un analgésico antiinflamatorio no esteroideo, asociado en reportes de casos clínicos con hepatotoxicidad. Sin embargo, se han publicado pocos estudios controlados en animales. Objetivo: Determinar si la administración de dosis terapéuticas de nimesulide, durante diferentes periodos, altera el funcionalismo hepático en ratas Wistar machos y hembras. Materiales y métodos: Cuarenta ratas Wistar fueron distribuidas en 4 grupos de 10 cada uno (5 hembras y 5 machos). Grupo I (control): recibió 0.1 mL de solución salina durante 7 días, los animales de los grupos II, III y IV fueron tratados con nimesulide (3 mg/kg) durante 7, 21 y 35 días, respectivamente. Se determinaron niveles séricos de bilirrubina, fosfatasa alcalina y transaminasas. Resultados: La actividad de la enzima alanino-amino-transferasa (ALT) aumentó en machos (p< 0.01) y hembras (p < 0.02) de los grupos III y IV respecto a los controles. En los machos de los grupos II y IV aumentó la fosfatasa alcalina en comparación con las hembras de los mismos grupos (p < 0.05). Las bilirrubinas di - recta y total disminuyeron en las hembras del grupo IV respecto al control (p < 0.03). Conclusiones: Los resultados sugieren que a dosis terapéuticas el nimesulide altera el funcionalismo hepático en ratas Wistar.

Introduction: Nimesulide is a non-steroidal antiinfflamatory drug associated with hepatotoxicity. Nevertheless, there have few published controlled studies with animals. Objec - tive: Determine whether the administration of therapeutic doses of nimesulide during differents periods alters hepatic function in male and female rats. Materials and me - thods: Forty Wistar rats were classified into 4 groups of 10 rats each. Group I received 0,1 ml of saline for 7 days, whe reas the animals from groups II, III and IV were treated with Ni mesulide (3 mg/kg) during 7, 21 and 35 days, respectively. It has determined serum levels of bilirubin, alkaline phos pha tase and transaminases. Results: Alanino-amino-transferase (ALT) enzyme was increased in males (p<0.01) and females (p<0.02) from groups III and IV in com parison with the control group. Alkalin phosphate increased in males from groups II and IV in comparison with the females from these same groups (p< 0.05). Direct and total bilirubins decreased in group IV females (p< 0.03) in comparison with the control group. Conclusions: The administration of therapeutic doses of nimesulide affects hepatic function on Wistar rats.