Spondias tuberosa Arr. (UMBU): estudo fitoquímico e avaliação do potencial anti-inflamatório

Spondias tuberosa Arruda (Anacardiaceae) is a fruitful tree popularly known as umbuzeiro, tapereba or umbu. It is a native and endemic species from Brazil, widespread in Brazilian Northeast. The species is important in folk medicine of the semi-arid Northeast, where it is mainly used to treat various inflammatory conditions, digestive problems as well as viral and bacterial infections. However, despite the common use in folk medicine, there are scarce pharmacological and phytochemicals studies that afford scientific evidence to its popular use. Therefore, this study aimed to characterize the chemical markers in S. tuberosa leaves extract, obtained by maceration ethanol:water (70:30, [v/v]), and evaluate its anti-inflammatory potential in vivo. The phytochemical profile in TLC analysis suggested the occurence of the flavonoids rutin and isoquercitrin. HPLC analysis enabled us to confirm the presence of flavonoids and also, were detected the phenolic acids, chlorogenic acid and caffeic acid. In addition was developed and validated a HPLC method to evaluate the content of the identified compounds in S. tuberosa leaves extract according to RDC 899/2003 of ANVISA and ICH Guidelines 2005. In order to evaluate the anti-inflammatory potential of S. tuberosa leaves extract, the peritonitis and paw edema models induced by carrageenan were used, administration i.p. in mice. The results highlighted the anti-inflammatory property in vivo at 125, 250 and 500 mg/kg since a decrease in leukocyte influx to the site of inflammation, diameter of the edema and the level of myeloperoxidase were observed when compared to the drug control dexamethasone (2 mg/kg, i.p. route). Taken together, the results pointed out S. tuberosa as a potential species for developing phytotherapic derivatives in according to its popular use. With regard to the characterization markers, chlorogenic acid, caffeic acid, rutin and isoquercitrin were identified and quantified in Spondias tuberosa leaves extract so they could be used in quality control analyses of the raw material and extracts of this species.

Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei

The occurrence of bioactive compounds in marine organisms comes awaking the interest of the pharmaceutical industry. Heparin, a sulfated polysaccharide which presence was already identified in several marine invertebrates, is very attractive due its remarkable functional versatility. Besides to intervene in blood coagulation, this molecule has a great anti-inflammatory potential. However, its strong anticoagulant activity difficult the clinical exploitation of its anti-inflammatory properties. Thus, the aims of this work were to evaluate the effect of a heparin-like compound (heparinoid), isolated from the cephalotorax of the Litopenaeus vannamei shrimp, on the inflammatory response, hemostasia and synthesis of antithrombotic heparan sulfate by endothelial cells, besides studying some aspects concerning its structure. The purified heparinoid was structurally characterized following an analytical boarding, involving electrophoresis and chromatography. The structural analysis have shown that this compound possess a high content of glucuronic acid residues and disulfated disaccharide units. In contrast to mammalian heparin, the heparinoid was incapable to stimulate the synthesis of heparan sulfate by endothelial cells in the tested concentrations, beyond to show reduced anticoagulant activity and hemorrhagic effect. In a model of acute inflammation, the compound isolated from the shrimp reduced more than 50% of the cellular infiltration. Besides reduce the activity of MMP-9 and proMMP-2 of the peritoneal lavage of inflamed animals, the heparinoid also reduced the activity of MMP-9 secreted by activated human leukocytes. These results demonstrate the potential of heparinoid from L. vannamei to intervene in the inflammatory response. For possessing reduced anticoagulant activity and hemorrhagic effect, this compound can serve as a structural model to direct the development of more specific therapeutical agents to the treatment of inflammatory diseases

Efeito de glucanas do fungo Caripia montagnei em modelo de inflamação intestinal induzida por tnbs em ratos Wistar e em células de carcinoma de cólon humano HT-29

Compounds derived from fungi has been the subject of many studies in order to broaden the knowledge of their bioactive potential. Polysaccharides from Caripia montagnei have been described to possess anti-inflammatory and antioxidant properties. In this study, glucans extracted from Caripia montagnei mushroom were chemically characterized and their effects evaluated at different doses and intervals of treatment. It was also described their action on colonic injury in the model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS), and its action on cells of the human colon carcinoma (HT-29). Compounds extracted of C. montagnei contain high level of carbohydrates (96%), low content of phenolic compounds (1.5%) and low contamination with proteins (2.5%). The (FT-IR) and (NMR) analysis showed that polysaccharides from this species of mushroom are composed of α- and β-glucans. The colonic damage was evaluated by macroscopic, histological, biochemical and immunologic analyses. The results showed a reduction of colonic lesions in all groups treated with the glucans of Caripia montagnei (GCM). GCM significantly reduced the levels of IL-6 (50 and 75 mg/kg, p < 0.05), a major inflammatory cytokine. Biochemical analyses showed that such glucans acted on reducing levels of alkaline phosphatase (75 mg/kg, p < 0.01), nitric oxide (p < 0.001), and myeloperoxidase (p < 0.001). These results were confirmed microscopically by the reduction of cellular infiltration. The increase of catalase activity suggest a protective effect of GCM on colonic tissue, confirming their anti-inflammatory potential. GCM displayed cytostatic activity against HT-29 cells, causing accumulation of cells in G1 phase, blocking the cycle cell progression. Those glucans also showed ability to modulate the adhesion of HT-29 cells to Matrigel® and reduced the oxidative stress. The antiproliferative activity against HT-29 cells displayed by GCM (p <0.001) can be attributed to its cytostatic activity and induction of apoptosis by GCM

Caracterização dos marcadores químicos e avaliação de atividades biológicas do extrato de Spondias mombim

Spondias mombin is a fruitful species dispersed in tropical regions of America, Africa and Asia. In Brazil, the species can be found mainly in the northern and northeastern regions. Scarce chemical and pharmacological studies have been reported for S. mombin and until this moment studies about chemical markers were not developed. In this context, the aims of this study were to characterize the chemical markers from S. mombin leaves and evaluate their anti-inflammatory, antioxidant and antiproliferative potentials. The chemical profile of the hydroethanolic extract from S. mombin leaves analyzed by HPLC-DAD, through a validated method, allowed the identification and quantification of ellagic acid and chlorogenic acid. This extract showed anti-inflammatory potential in acute peritonitis model induced by carrageenan. The hydroethanolic extract from S. mombin leaves was subjected to a liquid-liquid partition with the solvents: n-hexane, dichloromethane, ethyl acetate and n-butanol. Regarding the anti-inflammatory potential of the fractions obtained they were active; however, ethyl acetate fraction at 200 mg/kg showed highlighted results. The compounds ellagic acid and chlorogenic acid also inhibited the leukocyte migration to the site of inflammation at 2.5, 5 and 10 mg/kg. The hydroethanolic extract, fractions and the chemical markers showed significant antioxidant potential when evaluated in different assays: DPPH Free-Radical Scavenging, Superoxide Radical Scavenging, Hydroxyl Radicals Scavenging and Reducing Power. Taken together our results showed that hydroethanolic extract of S. mombin leaves has ellagic acid and chlorogenic acid as bioactive markers and it demonstrated antiinflammatory and antioxidant properties besides no cytotoxicity against 3T3 cells. It enables us to suggest S. mombin as an important species to develop herbal drugs

Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei

The occurrence of bioactive compounds in marine organisms comes awaking the interest of the pharmaceutical industry. Heparin, a sulfated polysaccharide which presence was already identified in several marine invertebrates, is very attractive due its remarkable functional versatility. Besides to intervene in blood coagulation, this molecule has a great anti-inflammatory potential. However, its strong anticoagulant activity difficult the clinical exploitation of its anti-inflammatory properties. Thus, the aims of this work were to evaluate the effect of a heparin-like compound (heparinoid), isolated from the cephalotorax of the Litopenaeus vannamei shrimp, on the inflammatory response, hemostasia and synthesis of antithrombotic heparan sulfate by endothelial cells, besides studying some aspects concerning its structure. The purified heparinoid was structurally characterized following an analytical boarding, involving electrophoresis and chromatography. The structural analysis have shown that this compound possess a high content of glucuronic acid residues and disulfated disaccharide units. In contrast to mammalian heparin, the heparinoid was incapable to stimulate the synthesis of heparan sulfate by endothelial cells in the tested concentrations, beyond to show reduced anticoagulant activity and hemorrhagic effect. In a model of acute inflammation, the compound isolated from the shrimp reduced more than 50% of the cellular infiltration. Besides reduce the activity of MMP-9 and proMMP-2 of the peritoneal lavage of inflamed animals, the heparinoid also reduced the activity of MMP-9 secreted by activated human leukocytes. These results demonstrate the potential of heparinoid from L. vannamei to intervene in the inflammatory response. For possessing reduced anticoagulant activity and hemorrhagic effect, this compound can serve as a structural model to direct the development of more specific therapeutical agents to the treatment of inflammatory diseases

Efeito de glucanas do fungo Caripia montagnei em modelo de inflamação intestinal induzida por tnbs em ratos Wistar e em células de carcinoma de cólon humano HT-29

Compounds derived from fungi has been the subject of many studies in order to broaden the knowledge of their bioactive potential. Polysaccharides from Caripia montagnei have been described to possess anti-inflammatory and antioxidant properties. In this study, glucans extracted from Caripia montagnei mushroom were chemically characterized and their effects evaluated at different doses and intervals of treatment. It was also described their action on colonic injury in the model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS), and its action on cells of the human colon carcinoma (HT-29). Compounds extracted of C. montagnei contain high level of carbohydrates (96%), low content of phenolic compounds (1.5%) and low contamination with proteins (2.5%). The (FT-IR) and (NMR) analysis showed that polysaccharides from this species of mushroom are composed of α- and β-glucans. The colonic damage was evaluated by macroscopic, histological, biochemical and immunologic analyses. The results showed a reduction of colonic lesions in all groups treated with the glucans of Caripia montagnei (GCM). GCM significantly reduced the levels of IL-6 (50 and 75 mg/kg, p < 0.05), a major inflammatory cytokine. Biochemical analyses showed that such glucans acted on reducing levels of alkaline phosphatase (75 mg/kg, p < 0.01), nitric oxide (p < 0.001), and myeloperoxidase (p < 0.001). These results were confirmed microscopically by the reduction of cellular infiltration. The increase of catalase activity suggest a protective effect of GCM on colonic tissue, confirming their anti-inflammatory potential. GCM displayed cytostatic activity against HT-29 cells, causing accumulation of cells in G1 phase, blocking the cycle cell progression. Those glucans also showed ability to modulate the adhesion of HT-29 cells to Matrigel® and reduced the oxidative stress. The antiproliferative activity against HT-29 cells displayed by GCM (p <0.001) can be attributed to its cytostatic activity and induction of apoptosis by GCM

Avaliação das atividades anti-inflamatória, anticoagulante e antiproliferativa do inibidor de quimotripsina das sementes de erythrina velutina (EvCI)

Studies indicate that several components were isolated from medicinal plants, which have antibacterial, antifungal, antitumor and anti-inflammatory properties. Sepsis is characterized by a systemic inflammation which leads to the production of inflammatory mediators exacerbated by excessive activation of inflammatory cells and disseminated intravascular coagulation (DIC), in which the human neutrophil elastase plays an important role in its pathogenesis. Several epidemiological studies suggest that components of plants, especially legumes, can play a beneficial role in reducing the incidence of different cancers. A chymotrypsin inhibitor of Kunitz (Varela, 2010) was purified from seeds of Erythrina velutina (Mulungu) by fractionation with ammonium sulfate, affinity chromatography on Trypsin-Sepharose, Chymotrypsin-Sepharose and ion exchange chromatography on Resource Q 1 ml (GE Healthcare) in system FPLC / AKTA. The inhibitor, called EvCI, had a molecular mass of 17 kDa determined by SDS-PAGE. The purified protein was able to inhibit human neutrophil elastase (HNE), with an IC50 of 3.12 nM. The EvCI was able to inhibit both pathways of HNE release stimulated by PAF and fMLP (75.6% and 65% respectively). The inhibitor also inhibited leukocyte migration in septic mice about 87% and prolonged the time of coagulation and inhibition factor Xa. EvCI showed neither hemolytic activity nor cytotoxicity. EvCI showed a selective antiproliferative effect to HepG2 cell lines with IC50 of 0.5 micrograms per milliliter. These results suggest EvCI as a molecule antagonist of PAF / fMLP and a potential use in fighting inflammation related disorders, disseminated intravascular coagulation (DIC) and cancer

Propriedades antioxidante, anti-hemostástica e antiproliferativa de galactanas sulfatadas da alga vermelha hypnea musciformis (wulfen) j. V. Lamouroux

Marine algae are one of the major sources of biologic compounds. In extracellular matrix of these organisms there are sulfated polysaccharides that functions as structural components and provides protection against dehydration. The fraction 1.0 (F1.0) rich in sulfated galactans obtained from red seaweed Hypnea musciformis was physicochemical characterized and evaluated for pharmacologic activity through antioxidant activity, cytotoxic action on erythrocytes, anticoagulant, stimulatory action under antithrombotic heparan sulfate synthesis and their effects on cell proliferation and cycle cell progression. The main components of F1.0 were carbohydrates (49.70 ± 0.10%) and sulfate (44.59 ± 0.015%), presenting phenolic compounds (4.79 ± 0.016%) and low protein contamination (0.92 ± 0.001%). Fraction 1.0 showed polidisperse profile and signs in infrared analysis in 1262, 1074 and 930, 900 and 850 attributed to sulfate esters S=O bond, presence of a 3,6- anidrogalactose C-O bond, non-sulfated β-D-galactose and a C-O-SO4 bond in galactose C4, respectively. The fraction rich in sulfated galactans exhibited strong antioxidant action under lipid peroxidation assay with IC50 of 0.003 mg/mL. Besides the inhibition of hemolysis induced by H2O2 in erythrocytes treated with F1.0, this fraction did not promote significant cytotoxity under erythrocytes membranes. F1.0 exhibited low anticoagulant activity causing moderate direct inhibition of enzimatic activity of thrombin. This fraction promoted stimulation around of 4.6 times on this synthesis of heparan sulfate (HS) by rabbit aortic endothelial cells (RAEC) in culture when was compared with non treated cells. The fraction of this algae displayed antiproliferative action under RAEC cells causing incresing on cell number on S fase, blocking the cycle cell progression. Thus F1.0 presented cytostatic and no cytotoxic action under this cell lineage. These results suggest that F1.0 from H. musciformis have antioxidant potential which is a great effect for a compound used as food and in food industry which could be an alternative to food industry to prevent quality decay of lipid containing food due to lipid peroxidation. These polysaccharides prevent the lipid peroxidation once the fraction in study exhibited strong inhibitory action of this process. Furthermore that F1.0 present strong antithrombotic action promoting the stimulation of antithrombotic HS synthesis by endothelial cells, being important for thrombosis preventing, by its inhibitory action under reactive oxygen species (ROS) in some in vitro methods, being involved in promotion of hypercoagulability state.

Avaliação do potencial anti-inflamatório de composto tipo heparina (cCTH) extraído do caranguejo Goniopsis cruentata em modelo experimental de peritonite

Heparin, a sulfated polysaccharide, was the first compound used as an anticoagulant and antithrombotic agent. Due to their structural characteristics, also has great potential anti-inflammatory, though such use is limited in inflammation because of their marked effects on coagulation. The occurrence of heparin-like compounds that exhibit anticoagulant activity decreased in aquatic invertebrates, such as crab Goniopsis cruentata, sparked interest for the study of such compounds as anti-inflammatory drugs. Therefore, the objective of this study was to evaluate the potential modulator of heparin-like compound extracted from Goniopsis cruentata in inflammatory events, coagulation, and to evaluate some aspects of its structure. The heparin-type compound had a high degree of N-sulphation in its structure, being able to reduce leukocyte migration into the peritoneal cavity at lower doses compared to heparin and diclofenac sodium (anti-inflammatory commercial). Furthermore, it was also able to inhibit the production of nitric oxide and tumor necrosis factor alpha by activated macrophages, inhibited the activation of the enzyme neutrophil elastase in low concentrations and showed a lower anticoagulant effect in high doses as compared to porcine mucosal heparin. Because of these observations, the compound extracted from crab Goniopsis cruentata can be used as a structural model for future anti-inflammatory agents

Atividades antinociceptiva e anti-inflamatória de uma fração rica em heterogalactana sulfatada extraída da alga codium isthmocladum (vickers 1905)

Sulfated polysaccharides comprise a complex group of macromolecules with a range of several biological activities, including antiviral activity, anticoagulant, antiproliferative, antiherpética, antitumor, anti-inflammatory and antioxidant. These anionic polymers are widely distributed in tissues of vertebrates, invertebrates and algae. Seaweeds are the most abundant sources of sulfated polysaccharides in nature. The green algal sulfated polysaccharides are homo or heteropolysaccharides comprised of galactose, glucose, arabinose and/or glucuronic acid. They are described as anticoagulant, anti-inflammatory, antiviral, anti-angiogenic, antitumor compounds. However, there are few studies about elucidation and evaluation of biological/pharmacological effects of sulfated polysaccharides obtained from green algae, for example, there is only one paper reporting the antinociceptive activity of sulfated polysaccharides of these algae. Therefore this study aimed to obtain sulfated polysaccharides of green seaweed Codium isthmocladum and evaluates them as potential antinociceptive agents. Thus, in this study, the total extract of polysaccharides of green alga C. isthmocladum was obtained by proteolytic digestion, followed by fractionation resulting in five fractions (F0.3, F0.5, F0.7, F0.9 and F1.2) by sequential precipitation with acetone. Using the test of abdominal contractions we observed that the fraction F0.9 was the most potent antinociceptive aompound. F0.9 consists mainly of a sulfated heterogalactana. More specific tests showed that Fo.9 effect is dose and time dependent, reaching a maximum at 90 after administration (10 mg / kg of animal). F0.9 is associated with TRPV1 and TRPA1 receptors and inhibits painful sensation in animals. Furthermore, F0.9 inhibits the migration of lymphocytes induced peritonitis test. On the other hand, stimulates the release of NO and TNF-α. These results suggest that F0.9 has the potential to be used as a source of sulfated galactan antinociceptive and anti-inflammatory

Avaliação da atividade anti-Helicobacter pylori e citotóxica in vitro de extratos orgânicos obtidos das folhas de Encholirium spectabile e Syzygium cumini

Helicobacter pylori is a spiral, Gram negative, mobile, and microaerophilic bacteria recognized as a major cause of gastritis, ulcer, gastric cancer, and gastric low grade, B cell, mucosa – associated lymphoid tissue (MALT) lymphoma, constituting an important microorganism in medical microbiology. Its importance comes from the difficulty of treatment because the requirement of multiple drugs use, besides the increasing emergence of resistant and multiresistant strains to antibiotics used in th e clinic. In order to expand safe and effective therapeutic options , chemical studies on medicinal plants by obtaining extracts, fractions, isolated compounds or essential oils with some biological activity has been intensified . Given the above, the objective was to evaluate the inhi bitory activity of organic extracts derived from Syzygium cumini and Encholirium spectabile, with antiulcer history, and the essential oil, obtained from S. cumini, against H. pylori (ATCC 43504) by the disk diffusion method, for qualitative evaluation, an d determination of minimum inhibitory concentration (MIC) using the broth microdilution method, for quantitative analysis. Also was evaluated the extracts in vitro toxicity by a hemolytic assay using sheep red blood cells, and VERO and HeLa cells using the MTT assay to analyze cell viability. The extracts of both plant used in antimicrobial assays did not inhibit bacterial growth, however the essential oil of S. cumini (SCFO) proved effective, showing MIC value of 205 μg/mL (0.024 % dilution of the original oil). In the hemolytic assay, the same oil shows moderate toxicity, by promote 25% hemolysis at 1000 μg/mL. Regarding the cytotoxicity in cell culture, the SCFO, at 260 μg/mL, affected the cell viability around 80% of HeLa and 50% of VERO cells. So the oi l obtained from S. cumini leaves has antimicrobial activity against H. pylori and cytotoxicity potential, suggesting a source of new molecule drug candidates, since new stages of toxicity in vitro and in vivo, as well, chemical characterization be evaluate d. Moreover, the development of a prospective drug delivery system can result in a prototype to be used in preclinical tests.

Avaliação da atividade anti-inflamatória do extrato aquoso, frações e compostos identificados nos frutos de Hancornia Speciosa Gomes (Apocynaceae)

Hancornia speciosa Gomes (Apocynaceae), popularly known as ‘mangabeira’, has been used in folk medicine to treat inflammatory disorders, hypertension, dermatitis, diabetes, liver diseases and stomach disorders. Regarding the Hancornia speciosa fruits, the ethnobotany indicates its use especially for treating inflammation and tuberculosis. However, no study has been done so far to prove such biological activities. The objective was evaluation anti-inflammatory activity from the fruits of Hancornia speciosa Gomes (mangabeira). Aqueous extract was prepared by decoction, subsequently submitted the liquid-liquid fractionation. The secondary metabolites were identified by high performance liquid chromatography coupled with detector diode array (HPLC-DAD) and liquid chromatography diode array detector coupled with mass spectrometry (LC-DAD-MS). The anti-inflammatory properties of the aqueous extract, dichloromethane (CH2Cl2), ethyl acetate (EtOAc) and n-butanol (n-BuOH) fractions of the fruits from H. speciosa, as well as rutin and chlorogenic acid were investigated using in vitro and in vivo models. In vivo tests comprised the xylene-induced ear edema that was measured the formation of edema, carrageenan-induced peritonitis was evaluated the total leukocytes at 4h and zymosan-induced air pouch was measured the total leukocytes and differential cell count at 6, 24 and 48 hours, whereas in vitro tests were evaluated levels of cytokines IL-1β, IL-6, IL-12 and TNF-α using ELISA obtained of carrageenan-induced peritonitis model. The results showed the presence of rutin and chlorogenic acid were detected in the aqueous extract from H. speciosa fruits by HPLC-DAD and LC-DAD-ME. Furthermore, the aqueous extracts and fractions, as well as rutin and chlorogenic acid significantly inhibited the xilol-induced ear edema and reduced cell migration in the animal models such as carrageenan-induced peritonitis and zymosan-induced air pouch. In addition, reduced levels of cytokines IL-1β, IL-6, IL-12 and TNF-α were observed. This is the first study that demonstrated the anti-inflammatory effect of aqueous extract from Hancornia speciosa fruits against different inflammatory agents in animal models, suggesting that their bioactive molecules, especially rutin and chlorogenic acid contributing, at least in part, to the anti-inflammatory effect of aqueous extract. These findings support the widespread use of Hancornia speciosa in popular medicine and demonstrate that this aqueous extract has therapeutic potential for the development of a herbal drugs with anti-inflammatory properties.

Análise fitoquímica e avaliação das atividades anti-inflamatória, antipeçonhenta e citotóxica de extratos aquosos de Aspidosperma pyrifolium e Ipomoea asarifolia

Envenomation caused by venomous animals, mainly scorpions and snakes, are a serious matter of public health. Tityus serrulatus is considered the most venomous scorpion in South America because of the high level of toxicity of its venom. It is responsible for causing serious accidents, mainly with kids. The species Bothrops jararaca is a serpent that has in its venom a complex mixture of enzyme, peptides and other molecules. The toxins of the venom of B. jararaca induce local and systemic inflammatory responses. The treatment chosen to serious cases of envenomation is the intravenous administration of the specific antivenom. However, the treatment is not always accessible to those residents in rural areas, so that they use medicinal plant extracts as the treatment. In this context, aqueous extracts, fractions and isolated compounds of Aspidosperma pyrifolium (pereiro) and Ipomoea asarifolia (salsa, salsa-brava), used in popular medicine, were studied in this research to evaluate the anti-inflammatory activity in the peritonitis models induced by carrageenan and peritonitis induced by the venom of the T. serrulatus (VTs), and in the local oedema model and inflammatory infiltrate induced by the venom of the B. jararaca, administrated intravenously. The results of the assays of cytotoxicity, using the MTT, showed that the aqueous extracts from the plant species presented low toxicity to the cells that came from the fibroblast of the mouse embryo (3T3).The chemical analysis of the extracts by High Performance Liquid Chromatography revealed the presence of the rutin flavonoid, in A. pyrifoliu, and rutin, clorogenic acid and caffeic acid, in I. asarifolia. Concerning the pharmacological evaluation, the results showed that the pre-treatment using aqueous extracts and fractions reduced the total leukocyte migration to the abdominal cavity in the peritonitis model caused by the carrageenan and in the peritonitis model induced by the T. serulatus venom. Yet, these groups presented anti-oedematous activity, in the local oedema model caused by the venom of the B. jararaca, and reduced the inflammatory infiltrate to the muscle. The serum (anti-arachnid and anti-bothropic) specific to each venom acted inhibiting the inflammatory action of the venoms and were used as control. The compounds identified in the extracts were also tested and, similar to the plant extracts, showed meaningful anti-inflammatory effects, in the tested doses. Thus, these results are indicating the potential anti-inflammatory activity of the plants studied. This is the first research that evaluated the possible biological effects of the A. pyrifolium and I. asarifolia, showing the biological potential that these species have.

Avaliação das atividades anti-inflamatória, anticoagulante e antiproliferativa do inibidor de quimotripsina das sementes de erythrina velutina (EvCI)

Studies indicate that several components were isolated from medicinal plants, which have antibacterial, antifungal, antitumor and anti-inflammatory properties. Sepsis is characterized by a systemic inflammation which leads to the production of inflammatory mediators exacerbated by excessive activation of inflammatory cells and disseminated intravascular coagulation (DIC), in which the human neutrophil elastase plays an important role in its pathogenesis. Several epidemiological studies suggest that components of plants, especially legumes, can play a beneficial role in reducing the incidence of different cancers. A chymotrypsin inhibitor of Kunitz (Varela, 2010) was purified from seeds of Erythrina velutina (Mulungu) by fractionation with ammonium sulfate, affinity chromatography on Trypsin-Sepharose, Chymotrypsin-Sepharose and ion exchange chromatography on Resource Q 1 ml (GE Healthcare) in system FPLC / AKTA. The inhibitor, called EvCI, had a molecular mass of 17 kDa determined by SDS-PAGE. The purified protein was able to inhibit human neutrophil elastase (HNE), with an IC50 of 3.12 nM. The EvCI was able to inhibit both pathways of HNE release stimulated by PAF and fMLP (75.6% and 65% respectively). The inhibitor also inhibited leukocyte migration in septic mice about 87% and prolonged the time of coagulation and inhibition factor Xa. EvCI showed neither hemolytic activity nor cytotoxicity. EvCI showed a selective antiproliferative effect to HepG2 cell lines with IC50 of 0.5 micrograms per milliliter. These results suggest EvCI as a molecule antagonist of PAF / fMLP and a potential use in fighting inflammation related disorders, disseminated intravascular coagulation (DIC) and cancer

Propriedades antioxidante, anti-hemostástica e antiproliferativa de galactanas sulfatadas da alga vermelha hypnea musciformis (wulfen) j. V. Lamouroux

Marine algae are one of the major sources of biologic compounds. In extracellular matrix of these organisms there are sulfated polysaccharides that functions as structural components and provides protection against dehydration. The fraction 1.0 (F1.0) rich in sulfated galactans obtained from red seaweed Hypnea musciformis was physicochemical characterized and evaluated for pharmacologic activity through antioxidant activity, cytotoxic action on erythrocytes, anticoagulant, stimulatory action under antithrombotic heparan sulfate synthesis and their effects on cell proliferation and cycle cell progression. The main components of F1.0 were carbohydrates (49.70 ± 0.10%) and sulfate (44.59 ± 0.015%), presenting phenolic compounds (4.79 ± 0.016%) and low protein contamination (0.92 ± 0.001%). Fraction 1.0 showed polidisperse profile and signs in infrared analysis in 1262, 1074 and 930, 900 and 850 attributed to sulfate esters S=O bond, presence of a 3,6- anidrogalactose C-O bond, non-sulfated β-D-galactose and a C-O-SO4 bond in galactose C4, respectively. The fraction rich in sulfated galactans exhibited strong antioxidant action under lipid peroxidation assay with IC50 of 0.003 mg/mL. Besides the inhibition of hemolysis induced by H2O2 in erythrocytes treated with F1.0, this fraction did not promote significant cytotoxity under erythrocytes membranes. F1.0 exhibited low anticoagulant activity causing moderate direct inhibition of enzimatic activity of thrombin. This fraction promoted stimulation around of 4.6 times on this synthesis of heparan sulfate (HS) by rabbit aortic endothelial cells (RAEC) in culture when was compared with non treated cells. The fraction of this algae displayed antiproliferative action under RAEC cells causing incresing on cell number on S fase, blocking the cycle cell progression. Thus F1.0 presented cytostatic and no cytotoxic action under this cell lineage. These results suggest that F1.0 from H. musciformis have antioxidant potential which is a great effect for a compound used as food and in food industry which could be an alternative to food industry to prevent quality decay of lipid containing food due to lipid peroxidation. These polysaccharides prevent the lipid peroxidation once the fraction in study exhibited strong inhibitory action of this process. Furthermore that F1.0 present strong antithrombotic action promoting the stimulation of antithrombotic HS synthesis by endothelial cells, being important for thrombosis preventing, by its inhibitory action under reactive oxygen species (ROS) in some in vitro methods, being involved in promotion of hypercoagulability state.