Antiobesity, hepatoprotective and anti-hyperglycemic effects of a pharmaceutical formulation containing Cecropia pachystachya Trécul in mice fed with a hypercaloric diet.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Cecropia pachystachya Trécul (Urticaceae), known as embaúba, are used as hypoglycemic and for weight reduction in Brazilian traditional medicine. AIM OF THE STUDY: This study investigated the effects of a pharmaceutical formulation (ECP20) containing C. pachystachya extract on some metabolic alterations caused by a hypercaloric diet in mice. MATERIAL AND METHODS: Mice were randomly fed with a standard or hypercaloric diet and orally treated with ECP20 or vehicle for 13 weeks. Subsequently, adiposity, glucose intolerance, and the presence of nonalcoholic fatty liver disease were assessed. Adipose tissue and liver were collected after euthanasia and frozen at -80 °C for histological and antioxidant analyzes. The effect of ECP20 on the differentiation of 3T3-L1 pre-adipocytes was also investigated. RESULTS: Animals treated with ECP20 showed less weight gain, reduced glycemia, glucose tolerance restored, and hepatoprotective effect. Also, ECP20 presented significant in vivo antioxidant activity. Treatment of 3T3-L1 preadipocytes with ECP20 did not inhibit cellular differencing. CONCLUSIONS: Therefore, ECP20 presented promising effects in the control of obesity and related disorders. Considering that glucose intolerance and hyperglycemia are strong evidence for the development of type 2 diabetes, the findings corroborated the traditional use of C. pachystachya to treat this disease. The chlorogenic acid and the flavonoids orientin and iso-orientin, present in the extract, might be involved in the activities found.

Anti-inflammatory and antinociceptive activity of Siparuna guianensis Aublet, an amazonian plant traditionally used by indigenous communities.

ETHNOPHARMACOLOGICAL RELEVANCE: Siparuna guianensis Aublet leaves, known as negramina, are used by indigenous and local communities in Brazil and other countries in the Americas to treat pain and inflammatory diseases. AIM OF THE STUDY: To characterize the chemical constituents and to evaluate the antioxidant, anti-inflammatory, antinociceptive and locomotor activities of the dichloromethane fraction (DF) of S. guianensis leaves. Also, an acute oral toxicity test was accomplished. MATERIAL AND METHODS: The chemical characterization of DF was performed by ultra-high pressure liquid chromatography (UHPLC) analyses coupled with a high-resolution mass spectrometer. The antioxidant potential of DF was investigated using nitric oxide (NO) and hydroxyl radical (OH) scavenging test. The evaluation study of the anti-inflammatory activity was carried out in vitro by NO measurement in stimulated macrophages and, in vivo, by croton oil-induced ear edema, LPS-induced peritonitis, and zymosan-induced arthritis in mice. Different mechanisms of central and peripheral nociception were stimulated by acetic acid-induced writhing, formalin, and tail-flick tests. Besides that, the open field assay was performed. RESULTS: UHPLC analyses of DF showed the presence of a mixture of glycosylated and methoxylated flavonoids. DF was able to scavenge NO and OH radicals in vitro and showed anti-inflammatory activity by inhibiting NO production in LPS-stimulated murine macrophages. Oral administration of DF considerably inhibited the ear edema after croton oil application and reduced the leukocyte infiltrated in LPS-induced peritonitis. In the inflammatory intra-articular zymosan-induced process, DF showed a significant reduction in the inflammatory area and of the cells in the synovial and connective tissues adjacent to the joint. Also, DF was able to reduce the intra-articular edema. In nociception models, the oral administration of DF considerably inhibited the acetic acid-induced writhings. The formalin test showed that DF attenuated the licking time in both phases, which suggested that DF reduce the nociception by central and peripheral mechanisms. In the tail-flick test, DF showed no activity. Besides that, DF did not affect the animal locomotion, and no acute toxicity was observed. CONCLUSIONS: For the first time, the anti-inflammatory and antinociceptive activities of S. guianensis were reported, supporting its ethnopharmacological uses for some inflammatory diseases and painful conditions.

Folliculotropic mycosis fungoides: challenging clinical, histopathological and immunohistochemical diagnosis.

Mycosis fungoides is a cutaneous T-cell lymphoma with various clinical and pathological presentations. Early lesions are nonspecific, which hinders early diagnosis. The folliculotropic subtype is manifested as acneiform lesions, follicular papules or erythematous plaques mainly on the face, neck and upper trunk. Histopathology shows dense lymphocytic infiltrate surrounding and infiltrating the hair follicles. A case of difficult histopathological diagnosis with florid and unusual skin lesions mainly on the face is reported.

Effects of dimethylsulfoxide and pentoxifylline in the vitality of cutaneous flaps in rats.

OBJECTIVES: to verify the influence of dimethylsulfoxide and pentoxifylline on the vitality of cutaneous flaps in rats and the tissue repair process. METHODS: were studied 30 Wistar rats, submitting them to a 2cm wide by 8cm long dorsal cutaneous flap, of caudal base. We distributed the animals in three groups: Control Group (n=10) with application gauze moistened with 0.9% Saline in the flap bed for 30 seconds; Dimethylsulfoxide group (n=10), with administration of 1ml of 5% dimethylsulfoxide divided into five injections of 0.2ml in the transition of the flap segments; Pentoxifylline group (n=10), with administration of pentoxifylline 20mg/kg, diluted to 1ml and divided into five injections of 0.2ml in the transition of the flap segments. Drugs were administered intraoperatively, in a single dose and subcutaneously. We observed the skin flaps for changes in color and texture. On the 10th postoperative day, we checked the dimensions of viable and necrotic tissues, followed by excision of the specimen for histological analysis. RESULTS: the measurements of length of the viable and necrotic tissues between groups showed no differences. Histological analysis showed that the Dimethylsulfoxide group presented neovascularization, inflammatory infiltrate with leukocytes and more structured conjunctival stroma. The Pentoxifylline group showed neovascularization and inflammatory infiltrate, with moderate to intense granulation. The control group evolved with a higher rate of necrosis in the distal segment. CONCLUSION: dimethylsulfoxide and pentoxifylline influenced the vitality of the flap and the tissue repair process. However, they did not prevent necrosis macroscopically.

Effects of dimethylsulfoxide and pentoxifylline in the vitality of cutaneous flaps in rats / Efeitos do dimetilsulfóxido e da pentoxifilina na vitalidade de retalhos cutâneos em ratos

ABSTRACT Objectives: to verify the influence of dimethylsulfoxide and pentoxifylline on the vitality of cutaneous flaps in rats and the tissue repair process. Methods: were studied 30 Wistar rats, submitting them to a 2cm wide by 8cm long dorsal cutaneous flap, of caudal base. We distributed the animals in three groups: Control Group (n=10) with application gauze moistened with 0.9% Saline in the flap bed for 30 seconds; Dimethylsulfoxide group (n=10), with administration of 1ml of 5% dimethylsulfoxide divided into five injections of 0.2ml in the transition of the flap segments; Pentoxifylline group (n=10), with administration of pentoxifylline 20mg/kg, diluted to 1ml and divided into five injections of 0.2ml in the transition of the flap segments. Drugs were administered intraoperatively, in a single dose and subcutaneously. We observed the skin flaps for changes in color and texture. On the 10th postoperative day, we checked the dimensions of viable and necrotic tissues, followed by excision of the specimen for histological analysis. Results: the measurements of length of the viable and necrotic tissues between groups showed no differences. Histological analysis showed that the Dimethylsulfoxide group presented neovascularization, inflammatory infiltrate with leukocytes and more structured conjunctival stroma. The Pentoxifylline group showed neovascularization and inflammatory infiltrate, with moderate to intense granulation. The control group evolved with a higher rate of necrosis in the distal segment. Conclusion: dimethylsulfoxide and pentoxifylline influenced the vitality of the flap and the tissue repair process. However, they did not prevent necrosis macroscopically.

RESUMO Objetivos: verificar a influência do dimetilsulfóxido e da pentoxifilina na vitalidade e no processo de reparo tecidual de retalhos cutâneos em ratos. Método: foram estudados 30 ratos Wistar, nos quais foi confeccionado retalho cutâneo dorsal de 2cm de largura por 8cm de comprimento, de base caudal, e distribuídos em três grupos: Grupo Controle (n=10) com aplicação de gaze umedecida com solução salina a 0,9%, no leito do retalho, por 30 segundos; Grupo dimetilsulfóxido (n=10) com injeção de 1ml de dimetilsulfóxido a 5% divididos em cinco injeções de 0,2ml na transição dos segmentos do retalho; Grupo pentoxifilina (n=10) com injeção de 1ml pentoxifilina 20mg/kg, divididos em cinco injeções de 0,2ml na transição dos segmentos do retalho. Os fármacos foram administrados no transoperatório, em dose única e por via subcutânea. Os retalhos cutâneos foram observados quanto às alterações de cor e textura. No décimo dia de pós-operatório aferiu-se a dimensão do tecido viável e de necrose, seguido da exérese da peça para análise histológica. Resultados: a medida da dimensão de tecido viável e de necrose dos grupos não apresentou diferenças. A análise histológica mostrou que o grupo dimetilsulfóxido apresentou neovascularização, infiltrado inflamatório com leucócitos e estroma conjuntivo mais estruturado. O grupo pentoxifilina, mostrou neovascularização e infiltrado inflamatório com granulação moderada e intensa. O grupo controle evoluiu com maior índice de necrose no segmento distal. Conclusão: dimetilsulfóxido e pentoxifilina influenciaram na vitalidade do retalho e no processo de reparo tecidual. Entretanto, não evitaram a necrose macroscopicamente.

Folliculotropic mycosis fungoides: challenging clinical, histopathological and immunohistochemical diagnosis

Abstract Mycosis fungoides is a cutaneous T-cell lymphoma with various clinical and pathological presentations. Early lesions are nonspecific, which hinders early diagnosis. The folliculotropic subtype is manifested as acneiform lesions, follicular papules or erythematous plaques mainly on the face, neck and upper trunk. Histopathology shows dense lymphocytic infiltrate surrounding and infiltrating the hair follicles. A case of difficult histopathological diagnosis with florid and unusual skin lesions mainly on the face is reported.

Pereskia aculeata Miller leaves accelerate excisional wound healing in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Pereskia aculeata Miller (Cactaceae), known as Barbados gooseberry, are used as emollients and to treat skin wounds and inflammatory process in Brazilian traditional medicine. AIM OF THE STUDY: This study investigated the topical wound healing activity of gels containing the methanol extract (ME) and hexane fraction (HF) of the leaves of this plant in a model of excisional wound healing in mice. MATERIAL AND METHODS: Mice were anesthetized and excisional skin wounds were performed using a circular metal punch of 5mm diameter. Next, the animals were treated with 30µL of topical gel formulations containing the gel base (vehicle), HF 5% or ME 5%. The treatments were applied immediately after the injury and every 48h during 14 days. To verify the wound closure kinetics, a digital caliper was used throughout this period. Laser Doppler perfusion image (LDPI) was applied to evaluate the blood flow rate at the injury site. Microscopic examination of the skin tissues was performed by histopathological analysis with hematoxylin and eosin and Gomori trichrome staining. Picrosirius-red staining was also used for morphometric analysis for collagen quantification. RESULTS: Both HF and ME markedly accelerated the closeness of the skin wounds; however the HF activity was more evident, as this fraction induced the increase of blood flow rate and collagen deposition when statistically compared to the vehicle. The mice skin treated with HF and ME also showed less fibroplasia, blood vessels and inflammatory cells on the last day of experiment, which indicated a more advanced wound healing process. CONCLUSIONS: As the wound healing process was considerably accelerated, especially by HF gel formulation, the results of this study not only contributed to better understand the ethnopharmacological application of P. acuelata leaves, but also encouraged further investigations on how to explore the potential uses of this plant in skin therapies.

Early IFN-γ production together with decreased expression of TLR3 and TLR9 characterizes EAE development conditional on the presence of myelin.

Experimental autoimmune encephalomyelitis (EAE) is a model for the study of multiple sclerosis, which is an inflammatory and demyelinating disease of the central nervous system (CNS). Despite increased efforts to elucidate the function of toll-like receptors (TLRs) in autoimmune diseases of the CNS, the relative contribution of other factors, including the immunomodulatory properties of TLR signaling, role of the innate response and the presence or absence of myelin peptides remain unclear. The aim was to evaluate TLR expression in the CNS during EAE development by investigating the expression of TLRs in the initial phase of EAE and establishing correlations with the modulation of inflammatory factors. Mice were subcutaneously immunized at the tail base with 100 µg of myelin oligodendrocyte glycoprotein peptide (MOG35-55), emulsified in complete Freund's adjuvant (CFA) supplemented with 400 µg of attenuated Mycobacterium tuberculosis H37RA. Pertussis toxin (300 ng per animal) was intraperitoneally injected on the day of immunization and 48 h later. Another group (MOG(-)) received an equal emulsion of CFA and M. tuberculosis, without MOG35-55, and the same protocol of Pertussis toxin. The immunized mice presented signs of disease with increased IFN-γ production and presence of NK cells on Day 2 postimmunization and reduced the expression of TLR-3 and TLR-9. In the spinal cord, CCL5 and CCL20 were higher in EAE. This study establishes a correlation between TLR-3 and TLR-9 expression with the development of EAE. In addition, evidence of a role for the myelin peptide in targeting the innate inflammatory response to the CNS is presented.

In vivo wound healing activity of gels containing Cecropia pachystachya leaves.

OBJECTIVES: To evaluate the in-vivo wound healing and in-vitro antioxidant activity of gels containing the ethyl acetate extract of Cecropia pachystachya (ECP) 2% and 5%, and to perform the chemical fingerprint of ECP by HPLC-DAD. METHODS: The wound healing activity of the gels was evaluated for 21 days, using the excision model in rats followed by histopathological and histomorphometric analysis. The in-vitro antioxidant effect of ECP was investigated using 1-diphenyl-2-picrylhydrazyl, reducing power, ß-carotene bleaching and thiobarbituric acid reactive substances assays. Also, a HPLC analysis was performed to identify the chemical markers orientin, iso-orientin and chlorogenic acid. KEY FINDINGS: The group of animals treated with ECP 5% presented oedema and inflammatory infiltrate with less intensity than the other groups. Both ECP 2% and 5% gels showed less neovascularization and cellularity, and better tissue repair when compared to the control, which showed a younger and homogeneous tissue. CONCLUSIONS: This study had demonstrated that the ECP gels promoted the acceleration of the healing process when compared to the control group. Wound contraction, angiogenesis, epithelialization and the collagen deposition support further evaluation of C. pachystachya leaves in the topical treatment and management of skin wounds.

Microcystic adnexal carcinoma simulating scarring alopecia.

The microcystic adnexal carcinoma is a rare, locally aggressive malignant adnexal neoplasm associated with significant morbidity. It is often underdiagnosed due to clinical and histopathological resemblance with other cutaneous neoplasms and/or a combination of lack of familiarity associated with inadequate samples. We report a case with clinical hypothesis of scarring alopecia and histopathological diagnosis of microcystic adnexal carcinoma with favorable outcome in a follow-up of eleven years, after surgical treatment.

Topical application of the hexane fraction of Lacistema pubescens reduces skin inflammation and cytokine production in animal model.

OBJECTIVES: The aim of this study was to investigate the acute topical anti-inflammatory effect of the hexane fraction (HLP) of Lacistema pubescens in mice. METHODS: Ear oedema models induced by croton oil, arachidonic acid, phenol, histamine, ethyl phenyl propiolate and capsaicin. Histopathological analyses of ear tissue samples sensitized with croton oil were performed. Myeloperoxidase activity (MPO), the pro-inflammatory cytokine-inhibitory effect and dermatoxicity were also evaluated. KEY FINDINGS: HLP (1, 0.5 and 0.1 mg/ear) resulted in a substantial reduction in skin thickness or tissue weight on all models tested, except for capsaicin-induced ear oedema, similar to dexamethasone (0.1 mg/ear) and/or indomethacin (0.5 mg/ear). Histopathological analyses and neutrophil-mediated MPO activity confirmed the topical anti-inflammatory effect of HLP. In addition, HLP reduced IL-1ß, IL-6 and tumour necrosis factor-α cytokine levels. Sitosterol-rich fraction (SRF), obtained from HLP fractionation, reduced ear oedema on croton oil and phenol models at the same dose of dexamethasone (0.1 mg/ear). No dermotoxicity was observed. CONCLUSIONS: The mechanism of action of HLP was associated with the inhibition of several pro-inflammatory mediators, including cytokines, arachidonic acid metabolites and histamine, which suggested a glucocorticoid-like effect, reinforced by the presence of the steroid sitosterol. This is the first report on anti-inflammatory activity of L. pubescens leaves.

Pereskia aculeata Miller leaves present in vivo topical anti-inflammatory activity in models of acute and chronic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Pereskia aculeata Miller (Cactaceae), known as Barbados gooseberry, are used in Brazilian traditional medicine as emollients and to treat skin wounds and inflammation. This study investigated the topical anti-inflammatory activity of the hexane fraction (HF) obtained from the methanol extract of the leaves of this species in models of acute and chronic ear dermatitis in mice. MATERIAL AND METHODS: Mice ear edema was induced by topical application of croton oil, arachidonic acid, capsaicin, ethyl-phenylpropiolate and phenol; and by subcutaneous injection of histamine. Ear biopsies were obtained to determine the levels of IL-1ß, IL-6 and TNF-α cytokines by ELISA assay. Histopathological analysis was also performed to evaluate the HF activity in croton oil multiple application test. In addition, acute dermal irritation/corrosion test in rats was accomplished. HF chemical characterization was performed by GC-MS analysis. RESULTS: HF intensively reduced the inflammatory process induced by all irritant agents used, except for arachidonic acid. This activity is related, at least in part, to the reduction of IL-6 and TNF-α cytokines levels. Moreover, when the glucocorticoid receptor antagonist mifepristone was used, HF failed to respond to the croton oil application.The results strongly suggested a glucocorticoid-like effect, which was reinforced by the presence of considerable amounts of sterol compounds identified in HF. The acute dermal irritaton/corrosion test showed no signs of toxicity. CONCLUSIONS: This study showed that the acute and chronic anti-inflammatory activity of P. aculeata leaves is very promising, and corroborates to better understand their ethnopharmacological applications.

Microcystic adnexal carcinoma simulating scarring alopecia

The microcystic adnexal carcinoma is a rare, locally aggressive malignant adnexal neoplasm associated with signifi cant morbidity. It is often underdiagnosed due to clinical and histopathological resemblance with other cutaneous neoplasms and / or a combination of lack of familiarity associated with inadequate samples. We report a case with clinical hypothesis of scarring alopecia and histopathological diagnosis of microcystic adnexal carcinoma with favorable outcome in a follow-up of eleven years, after surgical treatment.

Different MOG(35-55) concentrations induce distinguishable inflammation through early regulatory response by IL-10 and TGF-ß in mice CNS despite unchanged clinical course.

Multiple sclerosis (MS) shows distinct clinical courses. Experimental autoimmune encephalomyelitis (EAE), a model to study multiple sclerosis, can be induced by different protocols, which show distinct cytokine and antibody production. The factors involved in this heterogeneity remain unclear. The relevance of MOG concentration in triggering a regulatory response in the chronic model of EAE is imprecise. The aim of this study was investigate if 100 or 300 µg of MOG(35-55) could induce different EAE profiles. Modifications in the concentration of MOG were able to change the patterns of chemokines, cytokines, percentage of cells, inflammatory infiltrate and the development of a regulatory response. However, these changes were unable to modify the intensity of response, which explains the chronic progression of the disease in both concentrations. The results presented in this study contribute to understanding the intricate mechanisms that trigger EAE and provide insights into the pathogenesis of various forms of MS.

Increase of glyoosaminoglycans and metalloprotenases 2 and 9 in liver extracelllular matrix on early stages of extrahepatic cholestaiis / Aumento de glicosaminoglicanos e metaloproteinases 2 e 9 na matriz extracelular de fígado em estágios iniciais de colestase extra-hepática

Context Cholestasis produces hepatocellular injury, leukocyte infiltration, ductular cells proliferation and fibrosis of liver parenchyma by extracellular matrix replacement. Objective Analyze bile duct ligation effect upon glycosaminoglycans content and matrix metalloproteinase (MMPs) activities. Methods Animals (6-8 weeks; n = 40) were euthanized 2, 7 or 14 days after bile duct ligation or Sham-surgery. Disease evolution was analyzed by body and liver weight, seric direct bilirubin, globulins, gamma glutamyl transpeptidase (GGT), alkaline phosphatase (Alk-P), alanine and aspartate aminotransferases (ALT and AST), tissue myeloperoxidase and MMP-9, pro MMP-2 and MMP-2 activities, histopathology and glycosaminoglycans content. Results Cholestasis caused cellular damage with elevation of globulins, GGT, Alk-P, ALT, AST. There was neutrophil infiltration observed by the increasing of myeloperoxidase activity on 7 (P = 0.0064) and 14 (P = 0.0002) groups which leads to the magnification of tissue injuries. Bile duct ligation increased pro-MMP-2 (P = 0.0667), MMP-2 (P = 0.0003) and MMP-9 (P<0.0001) activities on 14 days indicating matrix remodeling and establishment of inflammatory process. Bile duct ligation animals showed an increasing on dermatan sulfate and/or heparan sulfate content reflecting extracellular matrix production and growing mitosis due to parenchyma depletion. Conclusions Cholestasis led to many changes on rats’ liver parenchyma, as so as on its extracellular matrix, with major alterations on MMPs activities and glycosaminoglycans content. .

Contexto Colestase produz lesão hepatocelular, infiltração leucocitária, proliferação de células ductulares e fibrose do parênquima hepático por matriz extracelular. Objetivo Analisar os efeitos da ligação do ducto biliar sobre conteúdo de glicosaminoglicanos e atividade de metaloproteinases de matriz (MMP). Métodos Animais (6-8 semanas; n = 40) foram eutanasiados 2, 7 ou 14 dias após ligação do ducto biliar ou falsa ligação. A evolução da doença foi analisada por peso corporal e do fígado, concentrações séricas de bilirrubina direta, globulinas, gama glutamil transpeptidase (GGT), fosfatase alcalina (Alk-P), alanina e aspartato aminotransfesases (ALT e AST), alterações teciduais de mieloperoxidase e metaloproteinases (MMP-9, pro MMP-2 e MMP-2), histopatologia e conteúdo de glicosaminoglicanos. Resultados A colestase causou dano celular com elevação dos níveis séricos de globulinas, GGT, Alk-P, ALT e AST. Houve também infiltração leucocitária observada pelo aumento na atividade de mieloperoxidase nos grupos 7 (P = 0,0064) e 14 dias (P = 0,0002) o que leva ao aumento das lesões no tecido. Ligação do ducto biliar aumentou as atividades de pro MMP-2 (P = 0,0677), MMP-2 (P = 0,0003) e MMP-9 (P<0,0001) aos 14 dias indicando remodelamento da matriz e estabelecimento de processo inflamatório. Animais com ligação do ducto biliar mostraram um aumento do conteúdo de dermatam sulfato e/ou heparam sulfato refletindo a produção de matriz extracelular e aumento de mitose devido a depleção do parênquima hepático. Conclusões Colestase causou várias mudanças no parênquima hepático de ratos, bem como em sua matriz extracelular, com importantes alterações na atividade ...

Positive correlation between disease activity index and matrix metalloproteinases activity in a rat model of colitis.

CONTEXT: Inflammatory bowel disease, including ulcerative colitis and Crohn's disease, comprising a broad spectrum of diseases those have in common chronic inflammation of the gastrointestinal tract, histological alterations and an increased activity levels of certain enzymes, such as, metalloproteinases. OBJECTIVES: Evaluate a possible correlation of disease activity index with the severity of colonic mucosal damage and increased activity of metalloproteinases in a model of ulcerative colitis induced by dextran sulfate sodium. METHODS: Colitis was induced by oral administration of 5% dextran sulfate sodium for seven days in this group (n=10), whereas control group (n=16) received water. Effects were analyzed daily by disease activity index. In the seventh day, animals were euthanized and hematological measurements, histological changes (hematoxylin and eosin and Alcian Blue staining), myeloperoxidase and metalloproteinase activities (MMP-2 and MMP-9) were determined. RESULTS: Dextran sulfate sodium group showed elevated disease activity index and reduced hematological parameters. Induction of colitis caused tissue injury with loss of mucin and increased myeloperoxidase (P<0.001) and MMP-9 activities (45 fold) compared to the control group. CONCLUSIONS: In this study, we observed a disease activity index correlation with the degree of histopathological changes after induction of colitis, and this result may be related mainly to the increased activity of MMP-9 and mieloperoxidase.

Chromatographic fingerprint analysis and effects of the medicinal plant species Mitracarpus frigidus on adult Schistosoma mansoni worms.

The aims of this work were to evaluate the in vitro and in vivo schistosomicidal properties of the methanolic extract of the aerial parts of Mitracarpus frigidus (MFM) and to determine its HPLC profile. For the in vitro experiment, four pairs of adult worms, obtained from infected mice, were exposed to different concentrations of MFM (100 to 400 µg/mL) for 24 and 48 h and analyzed under an inverted microscope. For the in vivo experiment, mice were inoculated with cercariae and, 20 days after infection, MFM (100 and 300 mg/kg) was administered orally for the following 25 days. Mice were euthanized after 60 days. MFM showed in vitro schistosomicidal activity, exhibiting the opening of the gynaecophoral canal of some male schistosomes, the presence of contorted muscles, vesicles, and the darkening of the paired worms skin. In vivo experiments showed that MFM treatments significantly reduced total worm count, as praziquantel, showing a decrease in liver and spleen weight. Also, a significant reduction in granuloma density was observed. MFM treatment did not cause alterations in the liver function of either infected or noninfected mice. The HPLC chromatogram profile showed the presence of kaempferol-O-rutinoside, rutin, kaempferol, psychorubrin, and ursolic acid.

Cecropia pachystachya: a species with expressive in vivo topical anti-inflammatory and in vitro antioxidant effects.

Cecropia pachystachya is a species traditionally used in Brazil to treat inflammation. This work aims to evaluate the topical anti-inflammatory and antioxidant activities of the methanolic extract of C. pachystachya (CPM) and to perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation induced by multiple application of croton oil. The in vitro antioxidant effect of CPM was investigated using DPPH, reducing power, ß -carotene bleaching, and TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM exhibited significant anti-inflammatory effect in the acute models, in some cases comparable to the reference drugs. Histopathological analysis showed a moderate chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell infiltration, and epidermal hyperproliferation. It also showed strong in vitro antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid were 66.5 ± 1.8, 118.8 ± 0.7, and 5.4 ± 0.2 µg/mg extract, respectively. The topical anti-inflammatory activity of CPM could be based on its antioxidant properties, although other effects are probably involved, including COX inhibition and other mechanisms.

Positive correlttion between disease activity idex and matrix metalloproteinasses activity in a rat model of colitis / Correlação positiva entre índice de atividade de doença e metaloproteinase de matriz em modelo de colite em ratos

Context Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, comprising a broad spectrum of diseases those have in common chronic inflammation of the gastrointestinal tract, histological alterations and an increased activity levels of certain enzymes, such as, metalloproteinases. Objectives Evaluate a possible correlation of disease activity index with the severity of colonic mucosal damage and increased activity of metalloproteinases in a model of ulcerative colitis induced by dextran sulfate sodium. Methods Colitis was induced by oral administration of 5% dextran sulfate sodium for seven days in this group (n=10), whereas control group (n=16) received water. Effects were analyzed daily by disease activity index. In the seventh day, animals were euthanized and hematological measurements, histological changes (hematoxylin and eosin and Alcian Blue staining), myeloperoxidase and metalloproteinase activities (MMP-2 and MMP-9) were determined. Results Dextran sulfate sodium group showed elevated disease activity index and reduced hematological parameters. Induction of colitis caused tissue injury with loss of mucin and increased myeloperoxidase (P<0.001) and MMP-9 activities (45 fold) compared to the control group. Conclusions In this study, we observed a disease activity index correlation with the degree of histopathological changes after induction of colitis, and this result may be related mainly to the increased activity of MMP-9 and mieloperoxidase. .

Contexto Doenças inflamatórias intestinais, entre elas colite ulcerativa e doença de Crohn, compreendem um amplo espectro de doenças que apresentam em comum inflamação crônica do trato gastrointestinal, alterações histológicas e um aumento de atividade de determinadas enzimas, tais como, metaloproteinases. Objetivos Avaliar possível correlação do índice de atividade de doença em modelo de colite ulcerativa induzida por dextran sulfato de sódio com o grau de severidade de danos na mucosa colônica e aumento de atividade de metaloproteinases. Métodos Colite foi induzida por administração oral de dextran sulfato de sódio 5% durante sete dias no grupo (n = 10), enquanto que o grupo controle (n = 16) recebeu água. Efeitos foram analisados diariamente pelo índice de atividade de doença. No sétimo dia, os animais foram sacrificados e as medições hematológicas, alterações histológicas (hematoxilina e eosina e coloração de azul Alcian), mieloperoxidase e atividades de metaloproteinases (MMP-2 e MMP-9) foram determinados. Resultados Grupo dextran sulfato de sódio mostrou elevação no índice de atividade de doença e redução dos parâmetros hematológicos. A indução da colite causa lesão no tecido, com perda de mucina e aumento da mieloperoxidase (P<0,001) e as atividades MMP-9 (45 vezes) em comparação com o grupo de controle. Conclusões Neste estudo, observamos uma correlação do índice de atividade de doença com o grau de alterações histopatológicas após indução da colite por dextran sulfato de sódio, podendo associar este resultado ao aumento principalmente da atividade de MMP-9 e de mieloperoxidase. .