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1.
An Acad Bras Cienc ; 93(suppl 3): e20191101, 2021.
Article in English | MEDLINE | ID: mdl-34730736

ABSTRACT

This work describes a pharmacological screening of Brazilian medicinal plants through their anti-inflammatory and cytotoxicity activities. Cytotoxicity activity of Mouriri elliptica and Alchornea glandulosa as well as the drugs celecoxib and doxorubicin were evaluated in cultures of peritoneal macrophages. The immune system influence of these samples was analyzed by determining production/inhibition of NO, production of tumor necrosis factor-α and production of interleukin-10. Regarding the production/inhibition of NO, there was NO production by M. elliptica and NO inhibition when the cells were exposed to A. glandulosa; Macrophages generally produce more NO, plus TNF-α and less IL-10, when associated to the tumor phenomenon, characterizing the inflammation involved in cancer. A. glandulosa showed anti-inflammatory effect, inhibited NO production and it was associated with low TNF-α production, although not as low as the macrophages associated with celecoxib and doxorubicin. These cytokines were not different in animals with tumor. Celecoxib confirms its anti-inflammatory action by markedly inhibiting NO and TNF-α, but also inhibiting IL-10 which is an anti-inflammatory cytokine. Doxorubicin inhibited NO in a higher percentage in the group of animals with tumor, although the literature reports that this drug stimulates the production of NO and this collaborates with its cytotoxic effect.


Subject(s)
Antineoplastic Agents , Carcinoma , Plants, Medicinal , Animals , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Cytokines , Ecosystem , Nitric Oxide , Tumor Necrosis Factor-alpha
3.
Planta Med ; 85(11-12): 957-964, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30780165

ABSTRACT

Three new benzaldehyde derivatives, sporulosaldeins A - C (1: -3: ), and 3 new benzopyran derivatives, sporulosaldeins D - F (4: -6: ), were discovered from an endophytic fungus, Paraphaeosphaeria sp. F03, which was isolated from Paepalanthus planifolius leaves. Compounds 1: -6: were elucidated by 1- and 2-dimensional nuclear magnetic resonance experiments and high-resolution mass spectrometry analysis. The absolute configuration of compound 5: was determined through the comparison of experimental and calculated electronic circular dichroism data. Compounds 1: -6: were found to exhibit antifungal activity with minimum inhibitory concentration (MIC) values of 7.8 - 250 µg/mL and racemic mixture of compound 6: exhibited weak cytotoxicity against MCF-7 and LM3 with IC50 values of 34.4 and 39.2 µM, respectively.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Ascomycota/chemistry , Benzaldehydes/pharmacology , Benzopyrans/pharmacology , Cytotoxins/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Benzaldehydes/chemistry , Benzaldehydes/isolation & purification , Benzopyrans/chemistry , Benzopyrans/isolation & purification , Cell Line, Tumor , Cytotoxins/chemistry , Cytotoxins/isolation & purification , Endophytes , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mice , Microbial Sensitivity Tests , Molecular Structure
5.
Med Mycol ; 53(1): 69-89, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25362733

ABSTRACT

Mycoses are gaining increasing attention in modern medicine because of the increase in diseases associated with opportunistic fungal infections. Despite the recognized role of the immune system in the control of fungal infections, no antifungal vaccines are currently licensed for use in humans. However, numerous vaccine candidates are being developed in many laboratories, as proof of the renewed interest in integrating or replacing chemotherapy with vaccines to reduce antibiotic use and consequently limit drug resistance and toxicity. In the effort to use safer and simpler fungal antigens for vaccinations, adjuvants have become relevant as immunostimulators to elicit successful protective immune responses. To address the relevant role of adjuvants as determinants in the balance of vaccine efficacy and safety, an updated and critical review of the adjuvants used in preclinical antifungal vaccines is presented, and prospective trends are addressed. Selected recent papers and other historically relevant and innovative strategies using adjuvants in experimental fungal vaccines are highlighted.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Drug Delivery Systems , Fungal Vaccines/immunology , Mycoses/prevention & control , Drug Discovery/trends , Fungal Vaccines/administration & dosage , Humans , Mycoses/immunology
6.
Cell Adh Migr ; 8(1): 60-5, 2014.
Article in English | MEDLINE | ID: mdl-24589623

ABSTRACT

Integrin αvß3 is most likely the foremost modulator of angiogenesis among all known integrins. Recombinant disintegrin DisBa-01, originally obtained from snake venom glands, binds to αvß3, thereby significantly inhibiting adhesion and generating in vivo anti-metastatic ability. However, its function in mediator production is not clear. Here, we observed that the mediators VEGF-A, IL-8, and TGF-ß are not produced by human umbilical vein endothelial cells (HUVEC cell line) or monocyte/macrophage cells (SC cell line) when cells adhered to vitronectin. However, when exposed to DisBa-01, HUVECs produced higher levels of TGF-ß, and SC cells produced higher levels of VEGF-A. Nonetheless, HUVECs also showed an enhancement of apoptosis after losing adherence when exposed to disintegrin, which is a characteristic of anoikis. We propose that disintegrin DisBa-01 could be used to modulate integrin αvß3 functions.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Cytokines/biosynthesis , Disintegrins/pharmacology , Integrin alphaVbeta3/metabolism , Apoptosis/drug effects , Cell Adhesion , Cell Survival/drug effects , Cells, Cultured , Drug Screening Assays, Antitumor , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/physiology , Humans , Recombinant Proteins/pharmacology , Vitronectin/metabolism
7.
Immunol Invest ; 43(4): 370-90, 2014.
Article in English | MEDLINE | ID: mdl-24484374

ABSTRACT

Toll-like receptors (TLRs) play an important role in immunity, since they bind to pathogen surface antigens and initiate the immune response. However, little is known about the role of TLR-2 in the recognition of S. schenckii and in the subsequent immune response. Therefore, the aim of this study was to evaluate the involvement of TLR-2 in the immune response induced by S. schenckii. C57BL/6 mice (WT) and C57BL/6 TLR-2 knockout (TLR-2-/-) were used to evaluate, over a period of 10 weeks of sporotrichotic infection, the influence of TLR-2 over macrophages production of IL-1ß, IL-12 and TNF-α, their stimulation level by NO release and the production of IFN -γ, IL-6, IL-17 and TGF-ß by spleen cells. The results showed that the production of pro-inflammatory mediators and NO, TLR-2 interference is striking, since its absence completely inhibited it. IL-17 production was independent of TLR-2. The absence of Th1 response in TLR2-/- animals was concomitant with IL-17 production. Therefore, it can be suggested that TLR-2 absence interferes with the course of the infection induced by the fungus S. schenckii.


Subject(s)
Sporothrix/immunology , Sporotrichosis/immunology , Sporotrichosis/metabolism , Toll-Like Receptor 2/metabolism , Animals , Cytokines/biosynthesis , Disease Models, Animal , Female , Humans , Interleukin-12/biosynthesis , Interleukin-1beta/biosynthesis , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Mice , Mice, Knockout , Nitric Oxide/metabolism , Organ Size , Spleen/metabolism , Spleen/pathology , Toll-Like Receptor 2/genetics , Tumor Necrosis Factor-alpha/biosynthesis
8.
Z Naturforsch C J Biosci ; 68(7-8): 293-301, 2013.
Article in English | MEDLINE | ID: mdl-24066514

ABSTRACT

Palladium(II) complexes are an important class of cyclopalladated compounds that play a pivotal role in various pharmaceutical applications. Here, we investigated the antitumour, anti-inflammatory, and mutagenic effects of two complexes: [Pd(dmba)(Cl)tu] (1) and [Pd(dmba)(N3)tu] (2) (dmba = N,N-dimethylbenzylamine and tu = thiourea), on Ehrlich ascites tumour (EAT) cells and peritoneal exudate cells (PECs) from mice bearing solid Ehrlich tumour. The cytotoxic effects of the complexes on EAT cells and PECs were assessed using the 3-(4,5-dimethylthiazol-3-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The effects of the complexes on the immune system were assessed based on the production of nitric oxide (NO) (Griess assay) and tumour necrosis factor-alpha (TNF-alpha), interleukin-12 (IL-12), and interleukin-10 (IL-10) (ELISA). Finally the mutagenic activity was assessed by the Ames test using the Salmonella typhimurium strain TA 98. Cisplatin was used as a standard. The IC50 ranges for the growth inhibition of EAT cells and PECs were found to be (72.8 +/- 3.23) microM and (137.65 +/- 0.22) microM for 1 and (39.7 +/- 0.30) microM and (146.51 +/- 2.67) microM for 2, respectively. The production of NO, IL-12, and TNF-alpha, but not IL-10, was induced by both complexes and cisplatin. The complexes showed no mutagenicity in vitro, unlike cisplatin, which was mutagenic in the strain. These results indicate that the complexes are not mutagenic and have potential immunological and antitumour activities. These properties make them promising alternatives to cisplatin.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Carcinoma, Ehrlich Tumor/pathology , Palladium/pharmacology , Animals , Cell Line, Tumor , Mice , Nitric Oxide/metabolism
9.
Langmuir ; 29(19): 5878-88, 2013 May 14.
Article in English | MEDLINE | ID: mdl-23586677

ABSTRACT

A new highly luminescent europium complex with the formula [Eu(TTA)3(Bpy-Si)], where TTA stands for the thenoyltrifluoroacetone, (C4H3S)COCH2COCF3, chelating ligand and Bpy-Si, Bpy-CH2NH(CH2)3Si(OEt)3, is an organosilyldipyridine ligand displaying a triethoxysilyl group as a grafting function has been synthesized and fully characterized. This bifunctional complex has been grafted onto the surface of dense silica nanoparticles (NPs) and on mesoporous silica microparticles as well. The covalent bonding of [Eu(TTA)3(Bpy-Si)] inside uniform Stöber silica nanoparticles was also achieved. The general methodology proposed could be applied to any silica matrix, allowed high grafting ratios that overcome chelate release and the tendency to agglomerate. Luminescent silica-based nanoparticles SiO2-[Eu(TTA)3(Bpy-Si)], with a diameter of 28 ± 2 nm, were successfully tested as a luminescent labels for the imaging of Pseudomonas aeruginosa biofilms. They were also functionalized by a specific monoclonal antibody and subsequently employed for the selective imaging of Escherichia coli bacteria.


Subject(s)
Biofilms/growth & development , Escherichia coli/growth & development , Nanoparticles/chemistry , Organometallic Compounds/chemistry , Pseudomonas aeruginosa/growth & development , Silicon Dioxide/chemistry , Europium/chemistry , Luminescence , Organometallic Compounds/chemical synthesis , Organosilicon Compounds/chemistry , Particle Size , Surface Properties
10.
Immunol Invest ; 42(1): 36-48, 2013.
Article in English | MEDLINE | ID: mdl-23231043

ABSTRACT

Sporotrichosis is an infection caused by the dimorphic fungus Sporothrix schenckii. Toll-like receptors (TLRs) play an important role in immunity, since they bind to pathogen surface antigens and initiate the immune response. However, little is known about the role of TLR-2 and fungal surface antigens in the recognition of S. schenckii and in the subsequent immune response. This study aimed to evaluate the involvement of TLR-2 and fungal surface soluble (SolAg) and lipidic (LipAg) antigens in phagocytosis of S. schenckii and production of immune mediators by macrophages obtained from WT and TLR-2(-/-) animals. The results showed that TLR-2(-/-) animals had had statistical lower percentage of macrophages with internalized yeasts compared to WT. SolAg and LipAg impaired phagocytosis and immunological mediator production for both WT and TLR-2(-/-). The absence of TLR-2 led to lower production of the cytokines TNF-α, IL-1ß, IL-12 and IL-10 compared to WT animals. These results suggest a new insight in relation to how the immune system, through TLR-2, recognizes and induces the production of mediators in response to the fungus S. schenckii.


Subject(s)
Antigens, Fungal/immunology , Macrophages/immunology , Sporothrix/immunology , Sporotrichosis/immunology , Toll-Like Receptor 2/immunology , Animals , Cells, Cultured , Cytokines/metabolism , Female , Immunity, Innate , Inflammation Mediators/metabolism , Macrophages/microbiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Phagocytosis/immunology , Toll-Like Receptor 2/genetics
11.
Nat Prod Res ; 25(19): 1796-806, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21656418

ABSTRACT

One of the major disadvantages of the current cancer therapy is the suppression of the immune system. Brazilian flora is considered one of the most diverse in the world and many plants were found to contain active constituents that can be valuable sources of new drugs. The plant Indigofera suffruticosa was studied to determine its potential to stimulate the immune system and also to be effective against tumour cells. We investigated the effects of the alkaloidal fraction and the pure alkaloid indigo obtained from I. suffruticosa on macrophage activation by measuring nitric oxide (NO) and tumour necrosis factor-α (TNF-α) production. Cytotoxic activity was also evaluated against the two tumour murine cells lines, LM2 (breast adenocarcinoma) and LP07 (lung adenocarcinoma). The alkaloidal fraction induced a high NO production and a moderated TNF-α release. The pure indigo demonstrated an elevated NO and TNF-α production. The fraction and the pure compound also exhibited cytotoxic activity against both adenocarcinoma cell lines and indigo showed the strongest cytotoxic activity with IC50 value of 0.89 µg mL⁻¹ against LM2 and 1.44 µg mL⁻¹ against LP07. Our results presented the immunostimulatory and cytotoxic activity of I. suffruticosa, enhancing macrophage function and therefore contributing to the host defence against tumours.


Subject(s)
Adjuvants, Immunologic/pharmacology , Cytotoxins/pharmacology , Indigofera/chemistry , Plant Extracts/pharmacology , Adjuvants, Immunologic/chemistry , Alkaloids/pharmacology , Animals , Brazil , Cell Line, Tumor , Cytotoxins/chemistry , Drug Discovery , Indigo Carmine , Indoles/pharmacology , Inhibitory Concentration 50 , Macrophages/drug effects , Mice , Nitric Oxide/metabolism , Plant Extracts/chemistry , Tumor Necrosis Factor-alpha/metabolism
12.
J Med Food ; 14(10): 1244-53, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21663472

ABSTRACT

Alchornea glandulosa has traditionally been used in Brazilian folk medicine for the treatment of immune-inflammatory diseases and as an antiulcer agent to heal gastric ulcer and gastritis. Angiogenesis is a complex multistep process that consists of proliferation, migration, and anastomosis of endothelial cells and has a major role in the development of pathologic conditions, such as inflammatory diseases. To investigate a possible link between the anti-inflammatory activities and antiangiogenic effects of A. glandulosa ethyl acetate fraction (AGF), this study examined which features of the angiogenic process could be disturbed by this fraction. The antiangiogenic activity of AGF was determined in vitro by using human umbilical vein endothelial cells (HUVEC), and cell viability, proliferation, apoptosis, invasion, and capillary-like structures formation were addressed. To elucidate the mechanism of action, nuclear factor κB (NFκB), a transcription factor implicated in these processes, was also evaluated in HUVEC incubated with AGF. A significant decrease in proliferation, a relevant increase in apoptosis, and a strong reduction in invasion capacity (as assessed by bromodeoxyuridine, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and double-chamber assays, respectively) were observed. AGF also led to a drastic reduction in the number of capillary-like structures formed when HUVEC were cultured on growth factor-reduced Matrigel-coated plates. In addition, incubation of HUVEC with AGF resulted in reduced NFκB activity. These findings emphasize the antiangiogenic potential of AGF and support its therapeutic use for disorders that involve excessive angiogenesis, such as chronic inflammation and tumor growth.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Euphorbiaceae/chemistry , Human Umbilical Vein Endothelial Cells/drug effects , Plant Extracts/pharmacology , Acetates , Apoptosis/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Human Umbilical Vein Endothelial Cells/cytology , Humans , In Situ Nick-End Labeling , NF-kappa B/genetics , NF-kappa B/metabolism , Neoplasm Invasiveness , Neovascularization, Pathologic , Signal Transduction , Transcription Factors , Umbilical Veins
13.
J Periodontol ; 82(5): 676-82, 2011 May.
Article in English | MEDLINE | ID: mdl-21073330

ABSTRACT

BACKGROUND: Earlier studies have shown an association between obesity and periodontitis, which is mediated by cytokine production. The aim of this study is to assess the role of obesity as a modifying factor on periodontal clinical parameters and on circulating proinflammatory cytokine levels in subjects undergoing non-surgical periodontal treatment. METHODS: Twenty-seven obese subjects and 25 normal-weight subjects were enrolled in this study. Subjects in both groups had generalized chronic periodontitis. The periodontal parameters measured before and 3 months after non-surgical periodontal therapy were: visible plaque index, bleeding gingival index, bleeding on probing, probing depth, and clinical attachment level. In addition, subjects underwent anthropometric measurements and serum analyses of fasting glucose, glycated hemoglobin, interleukin-1ß, interleukin-6, tumor necrosis factor-α, and interferon-γ. RESULTS: Periodontal therapy significantly decreased visible plaque index, bleeding gingival index, bleeding on probing, probing depth of 4 to 6 mm, probing depth ≥7 mm, clinical attachment level of 4 to 6 mm, and clinical attachment level ≥7 mm in both groups (P ≤0.05). Circulating proinflammatory cytokines significantly decreased in obese and normal-weight subjects after periodontal treatment (P ≤0.05). However, interleukin-6 and tumor necrosis factor-α levels remained higher in obese subjects 3 months after treatment (P ≤0.05). CONCLUSION: Obesity does not seem to play a negative role by interfering in the improvement of the periodontal clinical response or decreasing circulating proinflammatory cytokine levels after periodontal treatment.


Subject(s)
Chronic Periodontitis/therapy , Obesity/complications , Adipose Tissue/pathology , Adult , Blood Glucose/analysis , Body Mass Index , Body Weight , Chronic Periodontitis/blood , Chronic Periodontitis/complications , Cytokines/blood , Dental Plaque Index , Female , Follow-Up Studies , Gingival Hemorrhage/therapy , Glycated Hemoglobin/analysis , Humans , Inflammation Mediators/blood , Interferon-gamma/blood , Interleukin-1beta/blood , Interleukin-6/blood , Male , Middle Aged , Obesity/blood , Periodontal Attachment Loss/therapy , Periodontal Index , Periodontal Pocket/therapy , Tumor Necrosis Factor-alpha/analysis , Waist Circumference , Waist-Hip Ratio
14.
Eur J Med Chem ; 45(11): 4863-8, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20724041

ABSTRACT

Complexes of the type trans-[PdX(2)(isn)(2)] {X = Cl (1), N(3) (2), SCN (3), NCO (4); isn = isonicotinamide} were synthesized and evaluated for in vitro antimycobacterial and antitumor activities. The coordination mode of the isonicotinamide and the pseudohalide ligands was inferred by IR spectroscopy. Single crystal X-ray diffraction determination on 2 showed that coordination geometry around Pd(II) is nearly square planar, with the ligands in a trans configuration. All the compounds demonstrated better in vitro activity against Mycobacterium tuberculosis than isonicotinamide and pyrazinamide. Among the complexes, compound 2 was found to be the most active with MIC of 35.89 µM. Complexes 1-4 were also screened for their in vitro antitumor activity towards LM3 and LP07 murine cancer cell lines.


Subject(s)
Antineoplastic Agents/pharmacology , Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Niacinamide/chemistry , Palladium/chemistry , Animals , Antineoplastic Agents/chemistry , Antitubercular Agents/chemistry , Cell Line, Tumor , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Magnetic Resonance Spectroscopy , Mice , Spectrophotometry, Infrared
15.
Pharm Biol ; 48(8): 878-82, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20673174

ABSTRACT

Mycobacterium tuberculosis is responsible for over 8 million cases of tuberculosis (TB) annually. Natural products may play important roles in the chemotherapy of TB. The antimycobacterial activity and the innate immune response of methanol (METH) and dichloromethane (DCM) extracts of Indigofera suffruticosa Miller (Fabaceae) were evaluated. We observed that the minimum inhibitory concentrations (MICs) for METH and DCM extracts were 125 and 1000 microg/mL, respectively. However, they were able to induce the innate immune response through the production of high levels of NO and TNF-alpha (p < 0.001) by peritoneal exudate cells (PECs). These results suggest that I. suffruticosa extracts may have an important immunological role in the control of TB once macrophage activity is induced by them.


Subject(s)
Anti-Bacterial Agents/pharmacology , Immunity, Innate/drug effects , Indigofera , Mycobacterium tuberculosis/drug effects , Plant Extracts/pharmacology , Animals , Anti-Bacterial Agents/isolation & purification , Cell Survival/drug effects , Cell Survival/immunology , Cells, Cultured , Immunity, Innate/immunology , Mice , Microbial Sensitivity Tests/methods , Mycobacterium tuberculosis/immunology , Plant Components, Aerial , Plant Extracts/isolation & purification
16.
Z Naturforsch C J Biosci ; 64(9-10): 664-72, 2009.
Article in English | MEDLINE | ID: mdl-19957434

ABSTRACT

The activities of perlatolic acid (1), atranorin (2), and lecanoric acid (3) and their derivatives, such as orsellinates and beta-methyl orsellinates obtained by alcoholysis, were assessed for stimulation of the release of hydrogen peroxide and nitric oxide in cultures of peritoneal macrophage cells from mice. The hydrogen peroxide production was estimated by oxidation of phenol red, while the Griess reagent was used to determine the nitric oxide production. 1 and 4-methoxy-ethyl orsellinate (XVII) were the compounds that induced the greatest release of H2O2, whereas n-pentyl orsellinate (IV), iso-propyl orsellinate (V), sec-butyl orsellinate (VI), and XVII induced a small release of NO. These results indicate that lichen products and their derivatives have potential immune-modulating activities.


Subject(s)
Hydrogen Peroxide/metabolism , Lichens/metabolism , Macrophages/metabolism , Nitric Oxide/metabolism , Plant Extracts/metabolism , Animals , Mice
17.
Rev. bras. farmacogn ; 19(4): 847-852, out.-dez. 2009. ilus, tab
Article in English | LILACS | ID: lil-542698

ABSTRACT

The effects of isolated compounds from Brazilian lichens and their derivatives on H2O2 and NO production were studied using murine macrophages as a part of an attempt to understand their possible immunomodulatory properties. The compound cytotoxicity was studied using MTT assay. Macrophage stimulation was evaluated by the determination of NO (Griess assay) and H2O2 (horseradish peroxidase/phenol red) in supernatants of peritoneal macrophage cultures of Swiss mice. This research demonstrated stimulatory activities of some phenolic compounds isolated from lichens and their derivatives on H2O2 and NO production. Structure-activity relationships suggest several synthetic directions for further improvement of immunological activity.


Os efeitos dos compostos isolados de líquens brasileiros e seus derivados na produção de NO e H2O2 foram estudados utilizando macrófagos murinos na tentativa de desvendar suas possíveis propriedades imunomodulatórias. A citotoxicidade dos compostos foi estudada utilizando o ensaio de MTT. A estimulação dos macrófagos foi avaliada através da determinação de NO (metodologia de Griess) e H2O2 (peroxidase de raíz forte/vermelho de fenol) no sobrenadante de culturas de macrófagos peritoneais de camundongos Swiss. Este estudo demonstrou atividade estimulante de alguns compostos fenólicos e seus derivados na produção de NO e H2O2. A relação estrutura atividade sugere inúmeras direções sintéticas para futuros melhoramentos da atividade imunológica.

18.
Immunology ; 128(2): 301-9, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19740386

ABSTRACT

Toll-like receptors have been implicated in the recognition of various pathogens, including bacteria, viruses, protozoa and fungi. However, no information is available about Toll-like receptor 4 (TLR4) participation in Sporothrix schenckii recognition and the consequent triggering of the immune response to this fungal pathogen. Following activation of TLRs by ligands of microbial origin, several responses are provoked, including reactions in immune cells that may lead them to produce signalling factors that trigger inflammation. The present study was designed to elucidate the role of TLR4 during the host response to S. schenckii. TLR4-deficient (C3H/HeJ) and control mice (C3H/HePas) were infected with S. schenckii yeast cells and immune response was assessed over 10 weeks by assaying production of pro-inflammatory mediator (nitric oxide and tumour necrosis factor-alpha) and anti-inflammatory cytokine (interleukin-10) by peritoneal macrophages and their correlation with apoptosis in peritoneal exudate cells. We found that both pro-inflammatory and anti-inflammatory mediators are reduced in TLR4-deficient mice, suggesting the involvement of this receptor in the recognition of this infectious agent. Translocation into the nucleus of nuclear transcription factor, nuclear factor-kappaB, was also evaluated and showed higher levels in TLR-4 normal mice, consistent with the results found for cytokine production. We are showing here, for the first time, the involvement of TLR4 in S. schenckii recognition. Taken together, our results demonstrate that the activation of peritoneal macrophages in response to S. schenckii lipid extracts has different responses in these two mouse strains which differ in TLR4 expression, suggesting an important role for TLR4 in governing the functions of macrophages in this fungal infection.


Subject(s)
Antigens, Fungal/immunology , Lipids/immunology , Macrophages, Peritoneal/immunology , Sporothrix/immunology , Sporotrichosis/immunology , Toll-Like Receptor 4/immunology , Animals , Apoptosis/immunology , Immune Tolerance/immunology , Inflammation Mediators/metabolism , Interleukin-10/biosynthesis , Macrophage Activation/immunology , Macrophages, Peritoneal/pathology , Male , Mice , Mice, Inbred C3H , Necrosis/immunology , Reactive Nitrogen Species/biosynthesis , Transcription Factor RelA/metabolism , Translocation, Genetic , Tumor Necrosis Factor-alpha/biosynthesis
19.
Eur J Med Chem ; 44(11): 4611-5, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19632008

ABSTRACT

The reactions between [Pd(C(2),N-dmba)(micro-X)](2) (dmba=N,N-dimethylbenzylamine; X=Cl, Br) and thiourea (tu) in the 1:2 molar ratio at room temperature resulted in the mononuclear compounds [Pd(C(2),N-dmba)(Cl)(tu)] (1) and [Pd(C(2),N-dmba)(Br)(tu)] (2), which were characterized by elemental analyses and infrared (IR), (1)H- and (13)C{(1)H} NMR spectroscopies. The crystal and molecular structures of 2 were determined by single-crystal X-ray diffraction. In vitro cytotoxicity assays of the compounds 1, 2, tu, dmba and cisplatin were carried out using two murine tumor cell lines, namely mammary adenocarcinoma (LM3) and lung adenocarcinoma (LP07). The compounds 1, 2, tu and dmba were also tested against Mycobacterium tuberculosis and their MIC values were determined.


Subject(s)
Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antitubercular/chemistry , Antibiotics, Antitubercular/pharmacology , Palladium/chemistry , Palladium/pharmacology , Animals , Cell Line, Tumor , Cell Survival/drug effects , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Infrared Rays , Magnetic Resonance Spectroscopy , Models, Molecular , Mycobacterium tuberculosis/drug effects , Thiourea/chemistry , Thiourea/pharmacology
20.
BMC Complement Altern Med ; 9: 15, 2009 May 22.
Article in English | MEDLINE | ID: mdl-19463163

ABSTRACT

BACKGROUND: Angiogenesis, a complex multistep process that comprehends proliferation, migration and anastomosis of endothelial cells (EC), has a major role in the development of pathologic conditions such as inflammatory diseases, tumor growth and metastasis. Brazilian flora, the most diverse in the world, is an interesting spot to prospect for new chemical leads, being an important source of new anticancer drugs. Plant-derived alkaloids have traditionally been of interest due to their pronounced physiological activities. We investigated the anti-angiogenic potential of the naturally occurring guanidine alkaloid pterogynidine (Pt) isolated from the Brazilian plant Alchornea glandulosa. The purpose of this study was to examine which features of the angiogenic process could be disturbed by Pt. METHODS: Human umbilical vein endothelial cells (HUVEC) were incubated with 8 muM Pt and cell viability, proliferation, apoptosis, invasion and capillary-like structures formation were addressed. Nuclear factor kappaB (NFkappaB), a transcription factor implicated in these processes, was also evaluated in HUVEC incubated with Pt. Quantifications were expressed as mean +/- SD of five independent experiments and one-way analysis of variance (ANOVA) followed by the Dunnet test was used. RESULTS: A significant decrease in proliferation and invasion capacity and an effective increase in apoptosis as assessed by bromodeoxyuridine (BrdU), double-chamber and terminal transferase dUTP nick end labeling (TUNEL) assay, respectively, have been found. Pt also led to a drastic reduction in the number of capillary-like structures formation when HUVEC were cultured on growth factor reduced-Matrigel (GFR-Matrigel) coated plates. In addition, incubation of HUVEC with Pt resulted in reduced NFkappaB activity. CONCLUSION: These findings emphasize the potential use of Pt against pathological situations where angiogenesis is stimulated as tumor development.


Subject(s)
Alkaloids/pharmacology , Angiogenesis Inhibitors/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Cell Proliferation/drug effects , Endothelial Cells/drug effects , Euphorbiaceae/chemistry , Guanidines/pharmacology , Plant Extracts/pharmacology , Alkaloids/chemistry , Alkaloids/isolation & purification , Analysis of Variance , Angiogenesis Inhibitors/isolation & purification , Antineoplastic Agents, Phytogenic/isolation & purification , Apoptosis/drug effects , Cell Line , Guanidines/chemistry , Guanidines/isolation & purification , Humans , In Situ Nick-End Labeling , NF-kappa B/antagonists & inhibitors , Neoplasm Invasiveness , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Leaves , Plants, Medicinal/chemistry , Umbilical Veins
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