RESUMO
OBJECTIVES: Chronic synovitis is the main characteristic of rheumatoid arthritis (RA), defined by the proliferation of synovial lining cells, an important source of chemokines and cytokines associated with inflammation. The aim of this study was to examine the influence of complement functional activity on the development of chronic synovitis. METHOD: The experiments were conducted in zymosan-induced arthritis (ZIA) provoked by intra-articular injection of 180 µg zymosan. Mice were treated with 10 ng/g body weight (bw) cobra venom factor (CVF) on days -3 and -2 or with 10 ng/g bw CVF on days 7, 12, and 17 of ZIA. The percentage of neutrophils (CD11b+Ly6G+), macrophages (F4/80), and complement 5 anaphylatoxin receptor (C5aR)-positive cells in the synovial fluid (SF) were determined by flow cytometry and the expression of C5aR and C3aR in the synovium was detected immunohistochemically. RESULTS: The induction of ZIA in the absence of complement activity strongly inhibited the development of synovitis. By contrast, complement activation during ZIA exacerbated chronic synovitis through an increase in macrophage infiltration, C5aR and C3aR expression in the joints, and C5aR expression on SF cells. Levels of C5a and soluble receptor activator of nuclear factor kappa B ligand (sRANKL) in the SF were elevated whereas neutrophil infiltration and levels of tumour necrosis factor (TNF)-α and interleukin (IL)-6 in the SF were unchanged. CONCLUSIONS: Our findings indicate an important role for functional complement activity in the maintenance of chronic synovitis in a model of RA. Antagonizing complement activation represents new possibilities for the amelioration of synovitis symptoms.
RESUMO
Extracellular enzymes secreted by Candida albicans are claimed to be virulence factors responsible for penetration of the yeast into host cells. Substances able to inhibit lipolytic and proteinase activities of the fungus might be of therapeutic use in some pathologic conditions caused by C. albicans. In the present work, we have tested the influence of the flavonoid compounds apigenin and kaempferol, the indole alkaloid ibogaine, and the protoberberine alkaloid berberine on the in vitro enzyme activity of C. albicans. The substances showed complex suppressive effects concerning the processes of adherence to epithelial cells, secreted aspartyl proteinase activity, and the rate of cell wall protein glycosylation. Apigenin and kaempferol were administered in systemic C. albicans infection, demonstrating an increased number of survivors by kaempferol. The application of apigenin, kaempferol, ibogaine, and berberine in cutaneous infection suppressed the symptoms and accelerated elimination of the yeast from the site of inoculation.
Assuntos
Antifúngicos/farmacologia , Ácido Aspártico Endopeptidases/metabolismo , Candida albicans/efeitos dos fármacos , Candida albicans/enzimologia , Candidíase/tratamento farmacológico , Espaço Extracelular/enzimologia , Alcaloides/farmacologia , Animais , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Candida albicans/metabolismo , Candidíase/microbiologia , Adesão Celular/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Feminino , Flavonoides/farmacologia , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/metabolismo , Células HT29 , Humanos , Lipase/antagonistas & inibidores , Lipase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
In the present study the effect of the indole alkaloid ibogaine on the in vitro lipolytic activity and adherence to epithelial cells of Candida albicans was investigated. The substance was administered intraperitoneally at a dose of 5 mg kg(-1) day(-1) in mice with disseminated and gastrointestinal C. albicans infections. Ibogaine significantly decreased the rate of mortality and the number of C. albicans c.f.u. recovered from the kidney, liver and spleen. Ibogaine interfered with the early stages of both disseminated and gastrointestinal C. albicans infections but did not reduce the number of C. albicans c.f.u. in the organs at the late phase of infections. The development of a specific immune response was not influenced by ibogaine, since the delayed-type hypersensitivity reaction to C. albicans and the production of interferon (IFN)-gamma were similar in control and ibogaine-treated mice. The combined use of amphotericin B plus ibogaine in the treatment of mice with gastrointestinal infection reduced organ colonization more strongly than each substance alone.
Assuntos
Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Gastroenteropatias/tratamento farmacológico , Ibogaína/farmacologia , Adesividade/efeitos dos fármacos , Anfotericina B/uso terapêutico , Animais , Antifúngicos/uso terapêutico , Encéfalo/microbiologia , Candida albicans/crescimento & desenvolvimento , Candida albicans/fisiologia , Candidíase/microbiologia , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Feminino , Gastroenteropatias/microbiologia , Hipersensibilidade Tardia , Ibogaína/administração & dosagem , Ibogaína/uso terapêutico , Injeções Intraperitoneais , Rim/microbiologia , Lipase/antagonistas & inibidores , Fígado/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Baço/microbiologiaRESUMO
The immune system generates a specific response against most pathogens, while developing tolerance to self-antigens. Commensal micro-organisms can express molecular structures that mimic self-epitopes. During acute infection, such pathogen may activate self-reactive T-cell clones promoting autoimmunity. In the present study, a beta-mercaptoethanol cell-wall fraction (MF) from Candida albicans was injected into the paw of naive ICR and BALB/c mice and into the paw of ICR mice with bovine collagen type II-induced arthritis (CIA). Development of inflammation was monitored for 6 weeks. MF provoked a stable swelling and histopathologic changes in the injected joint, with a predominance of T-helper 1 cytokines in ICR mice. In BALB/c strain, a swelling was observed only in the early period, with no evidence of joint pathology. Injection of the MF fraction exacerbated the disease in ICR mice with CIA, and this was associated with the elevation of interferon-gamma and anti-bovine type II collagen (bCII) immunoglobulin G2a antibodies. These results indicate that component(s) in the MF fraction cross-react with bCII-specific cells.
Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Candida albicans/imunologia , Proteínas Fúngicas/imunologia , Animais , Artrite Experimental/microbiologia , Artrite Experimental/patologia , Artrite Reumatoide/microbiologia , Artrite Reumatoide/patologia , Proliferação de Células , Parede Celular/imunologia , Colágeno Tipo II , Ensaio de Imunoadsorção Enzimática , Feminino , Histocitoquímica , Imunoglobulina G/sangue , Interferon gama/análise , Interleucina-10/análise , Interleucina-2/análise , Articulações/imunologia , Articulações/microbiologia , Articulações/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Baço/citologia , Baço/imunologia , Fator de Necrose Tumoral alfa/análiseRESUMO
OBJECTIVE AND DESIGN: To study the effect of the alkaloid fangchinoline on zymosan-induced multiple organ dysfunction syndrome (MODS) and Escherichia coli (E. coli)-induced septic shock. MATERIAL: Male ICR mice were used. Macrophages were isolated from peritoneal cavity for in vitro study. TREATMENT: Fangchinoline was administered i.p. at a dose of 1 or 5 mg/kg into the mice. METHODS: MODS was induced by intraperitoneal (i.p.) injection of zymosan at a dose 1.0 or 0.8/g b.w. E. coli-induced septic shock was provoked by i.p. inoculation of 5 x 10(8) bacterial cells into mice. TNF-alpha in serum and supernatants from peritoneal macrophages was detected by the use of L-929 cell cytotoxic assay. Alternative pathway (AP) complement activity was determined by hemolytic assay. RESULTS: Fangchinoline increased the survival rate in lethal MODS and septic shock. The alkaloid prevented the loss of body weight and liver enlargement in MODS and suppressed serum tumor necrosis factor-alpha (TNF-alpha) accumulation in MODS and septic shock. CONCLUSIONS: The result suggest that fangchinoline due mainly to its ability to downregulate TNF-alpha production might have protective effect in murine models of zymosan-induced MODS and E. coli-induced septic shock.
Assuntos
Alcaloides/uso terapêutico , Benzilisoquinolinas , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Fosfatase Alcalina/sangue , Animais , Proteínas do Sistema Complemento/biossíntese , Infecções por Escherichia coli/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/patologia , Macrófagos Peritoneais/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Tamanho do Órgão/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/patologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/análise , ZimosanRESUMO
Candida albicans, as an opportunistic pathogen, causes therapeutic problems in immunocompetent individuals and frequently it initiates severe infections in immunocompromised hosts. The application of a lysozyme digest preparation from the cell walls of Nocardia opaca (Nocardia lysozyme digest; NLD), recently classified as Rhodococcus opacus, has a protective effect in intravenous (i.v.) C. albicans infections in inbred ICR mice which have normal complement production. It also significantly reduces i.v. and intraperitoneal (i.p.) infections in DBA/2 mice which are deficient in C5 complement component. A significant decrease in C. albicans recovery from kidneys was found in NLD-treated DBA/2 animals. The preparation enhanced delayed type hypersensitivity to the yeast cells in both mouse strains. C. albicans-induced popliteal lymph node reactions were increased in ICR mice. In addition, mouse splenocytes that had been inhibited in their proliferative response to phytohaemagglutinin had this response restored after exposure to the preparation. NLD decreased the sensitivity of both mouse strains to a second challenge with the pathogen. The preparation restored the impaired host response to C. albicans infection in ICR mice treated with cobra venom and cyclophosphamide.
Assuntos
Candidíase/prevenção & controle , Muramidase/farmacologia , Nocardia/enzimologia , Animais , Feminino , Hipersensibilidade Tardia/prevenção & controle , Tolerância Imunológica , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos DBA , Camundongos Endogâmicos ICRRESUMO
Phytochemical study of leaves of Uvaria chamae resulted in the isolation for the first time for the genus Uvaria of benzylisoquinoline alkaloids (+)-armepavine (1) and racem. O,O-dimethylcoclaurine (2). The aporphines nornantenine (3), nantenine (4) and corydine (7) are new for the species. The alkaloids were found to express cytotoxic activity against L 929 transformed cells. The highest activity was shown by 1, 3, and 5. At a concentration corresponding to their IC50 against L929 cells, they were nontoxic against mouse thymocytes.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Plantas Medicinais/química , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sarcoma Experimental/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
The alkaloid oxoglaucine reduced CD4+ cell clones in adult mice and decreased CD4+, CD8+ and Ig+ levels in newborn mice. It prevented the increase of CD8+ and Ig+ clones induced by Candida albicans (C. albicans) in adult mice. TNF-alpha serum accumulation was inhibited by oxoglaucine in C. albicans infection and adjuvant arthritis. Treatment with oxoglaucine of arthritic mice, followed by inoculation with C. albicans enhanced the host resistance against the pathogen.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Apomorfina/análogos & derivados , Artrite Experimental/complicações , Candida albicans/efeitos dos fármacos , Candidíase/complicações , Animais , Apomorfina/imunologia , Apomorfina/uso terapêutico , Bioensaio , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Candidíase/tratamento farmacológico , Candidíase/imunologia , Feminino , Citometria de Fluxo , Camundongos , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Berberine (BB) is a protoberberine alkaloid derived from various representatives of the Berberidaceae family. Although used as a therapeutic agent, it has not been applied in the treatment of immune-mediated disorders. In the present study, BB was administered at a daily dose of 10 mg/kg for 3 consecutive days before the induction of tubulointerstitial nephritis (TIN) by injection of bovine tubular basement membrane (TBM) antigen in BALB/c mice. The animals were investigated 2 months after TBM inoculation. The intensity of pathological injuries in animals with TIN+BB decreased significantly, an effect that correlated with the improvement of renal function. Flow cytometric analysis of peripheral blood cells showed that BB caused a decrease in the number of CD3(+), CD4(+), CD8(+), and sIg(+) lymphocytes in comparison with TIN mice. The same tendency was noticed in the lymphocytes from kidney infiltrates of treated animals. The control animals treated only with BB showed a decrease in the number of CD3(+), CD4(+), CD8(+) T-lymphocytes in comparison with control nontreated mice. Our results, thus, indicate that BB has an immunosuppressive effect in the TIN model, which is an analogue of various human kidney autoimmune diseases.
Assuntos
Doenças Autoimunes/prevenção & controle , Alcaloides de Berberina/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Intersticial/prevenção & controle , Animais , Antígenos/imunologia , Membrana Basal/imunologia , Alcaloides de Berberina/administração & dosagem , Contagem de Linfócito CD4 , Imunossupressores/administração & dosagem , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos BALB C , Nefrite Intersticial/etiologia , Nefrite Intersticial/imunologiaRESUMO
The immunosuppressive action of aporphinoid alkaloid oxoglaucine was studied in experimental Candida albicans (C. albicans) infection in mice. The alkaloid augmented host resistance to pathogen applied to mice (6-8 weeks of age) at a low dose of 2 mg kg(-1)in 3 days and impaired it at a high dose of 10 mg kg(-1). The suppressive activity observed under the latter schedule correlated with the inhibited proliferative response of splenic cells to mitogens and with decreased popliteal lymph node (PLN) reaction to C. albicans. Treatment of mice with oxoglaucine (at the age of 5 days) at a dose of 5 mg kg(-1)in 3 consecutive days increased the susceptibility to Candida inoculation at the age of 6 weeks. Delayed type hypersensitivity (DTH) response to C. albicans was enhanced after pretreatment of adult mice and was suppressed after administration to newborn mice. Long-time treatment (10 days) with oxoglaucine, cyclophoshamide or prednisolone at a dose of 10 mg kg(-1)increased the rate of mortality of Candida -infected mice. Combined pretreatment of mice with cyclophosphamide or prednisolone (5 days at a dose of 5 mg kg(-1)) followed by oxoglaucine (5 days at a dose of 5 mg kg(-1)), prolonged the survival of infected mice. 2000 Academic Press@p$hr Copyright 2000 Academic Press.
RESUMO
The immunosuppressive action of aporphinoid alkaloid oxoglaucine was studied in experimental Candida albicans (C. albicans) infection in mice. The alkaloid augmented host resistance to pathogen applied to mice (6-8 weeks of age) at a low dose of 2 mg kg(-1) in 3 days and impaired it at a high dose of 10 mg kg(-1). The suppressive activity observed under the latter schedule correlated with the inhibited proliferative response of splenic cells to mitogens and with decreased popliteal lymph node (PLN) reaction to C. albicans. Treatment of mice with oxoglaucine (at the age of 5 days) at a dose of 5 mg kg(-1) in 3 consecutive days increased the susceptibility to Candida inoculation at the age of 6 weeks. Delayed type hypersensitivity (DTH) response to C. albicans was enhanced after pretreatment of adult mice and was suppressed after administration to newborn mice. Long-time treatment (10 days) with oxoglaucine, cyclophoshamide or prednisolone at a dose of 10 mg kg(-1) increased the rate of mortality of Candida-infected mice. Combined pretreatment of mice with cyclophosphamide or prednisolone (5 days at a dose of 5 mg kg(-1)) followed by oxoglaucine (5 days at a dose of 5 mg kg(-1)), prolonged the survival of infected mice.
Assuntos
Apomorfina/análogos & derivados , Candidíase/imunologia , Imunossupressores/farmacologia , Animais , Apomorfina/farmacologia , Encéfalo/microbiologia , Ciclofosfamida/farmacologia , Feminino , Hipersensibilidade Tardia , Rim/microbiologia , Linfonodos/imunologia , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICRRESUMO
The protoberberine alkaloid berberine is isolated as a main alkaloid from the roots and bark of Berberis vulgaris. Berberine strongly inhibited in vitro the proliferative response of mouse spleen cells to T-dependent mitogens concanavalin A (Con A) and phytochemagglutinin (PHA). Spleen cells obtained from berberine-treated mice (10 mg/kg/3 days) expressed enhanced proliferative response to both mitogens. Berberine was applied to mice at different intervals before or after the induction of adjuvant arthritis (AIA) and Candida albicans (C. albicans) infection. The application of the alkaloid to new born mice (5 days after birth at a dose of 5 mg/kg/3 days) did not change the course of AIA and C. albicans infection. Its application at three 10 day intervals (5 mg/kg), starting from the 5 day after birth increased the joint inflammation in AIA. The host resistance to C. albicans infection was not affected, while the delayed type hypersensitivity (DTH)-reaction against the pathogen was enhanced. The alkaloid inhibited the development of AIA when applied after its onset (10 mg/kg from day +3 to +12 day). Berberine treatment during the ongoing infection did not influence its outcome (from +2 to +10 day).
Assuntos
Berberina/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/imunologia , Animais , Artrite Experimental/imunologia , Candida albicans/imunologia , Candidíase/imunologia , Candidíase/mortalidade , Relação Dose-Resposta Imunológica , Feminino , Hipersensibilidade Tardia/imunologia , Imunossupressores/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Mitógenos/antagonistas & inibidores , Mitógenos/farmacologia , Baço/citologia , Baço/efeitos dos fármacosRESUMO
Eleven bisbenzylisoquinoline alkaloids (BBI) were isolated from the plant Isopyrum thalictroides (L.). Treatment of normal human serum (NHS) with BBI resulted in a diminution of the haemolytic activity of the classical pathway (CP). The mode of action of the main alkaloids isopyruthaline (It1), fangchinoline (It2) and isotalictrine (It3) on CP activation was investigated in vitro. The inhibition was time- and temperature-related and for Itl and It3 depended on the concentration of Ca2+ and Mg2+ ions. It was established that the substances reduced C1 haemolytic activity. It2 and It3 enhanced the complement consumption caused by heat aggregated human IgG (HAGG). The BBI prevented the formation of C3 convertase of the classical pathway. The loss of haemolytic activity was partially restored by the addition of C142 reagent (zymosan-treated guinea pig serum) to alkaloids-treated NHS. The addition of the late components C3-9 (EDTA-treated rat sera) recovered to some extent the haemolytic activity of It1-treated NHS, but not of It2- and It3-treated NHS.
Assuntos
Alcaloides/farmacologia , Proteínas Inativadoras do Complemento/farmacologia , Via Clássica do Complemento/efeitos dos fármacos , Isoquinolinas/farmacologia , Plantas Medicinais/química , Alcaloides/isolamento & purificação , Animais , Complemento C1/imunologia , Complemento C4/imunologia , Proteínas Inativadoras do Complemento/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Cobaias , Humanos , Isoquinolinas/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ratos , OvinosRESUMO
The main alkaloids isopyruthaline (It1), fangchinoline (It2) and isothalictrine (It3), isolated from Isopyrum thalictroides (L.) were investigated in complement-mediated reactions. The alkaloids influenced the alternative pathway (AP) activity in normal human serum (NHS). They enhanced the inhibitory action of complement activators--carrageenan (Car), zymosan (Zy), hydrogen peroxide (HP) and high temperature via classical pathway (CP) in NHS. Substances strongly potentiated the action of zymosan and cobra venom (CV) in guinea pig serum (GPS). It was established that they could provoke C3 conversion in NHS and mouse sera (MS). The antiinflammatory properties of the alkaloids were evaluated in mouse paw oedema induced by CV, Zy and histamine (His). Isopyruthaline and isothalictrine suppressed paw swelling in CV- and Zy-oedema. They were applied in Zy-induced multiple organ dysfunction syndrome (MODS) in mice. The alkaloids inhibited the increase of the serum complement activity provoked by the injection of zymosan. Itl lowered the mortality rate of mice with MODS if its application proceeded Zy. An increase of the number of mice without tissue injury was established after treatment with It1 and It3.
Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Benzilisoquinolinas , Proteínas Inativadoras do Complemento/farmacologia , Via Alternativa do Complemento/efeitos dos fármacos , Isoquinolinas/farmacologia , Plantas Medicinais/química , Alcaloides/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Proteínas Inativadoras do Complemento/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Edema/sangue , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/imunologia , Cobaias , Humanos , Isoquinolinas/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos ICR , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/imunologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologiaRESUMO
The inhibitory effect of 15 semi-synthetic analogues of glaucine (1) on the lipopolysaccharide (LPS)-induced and the concanavalin A (Con A)-induced proliferation of mouse splenocytes was compared in vitro. Isoboldine (3), bracteoline (4) and dehydroglaucine (9) showed a significantly higher potency to suppress LPS-induced proliferation than 1, while 7-hydroxy-4-methylglaucine (8), 7-formyldehydroglaucine (11), 7-acetyldehydroglaucine (13), 7-benzoyldehydroglaucine (14), oxoglaucine (15) and glaucine-quinol (16) were less inhibitory. Compounds 3, 4, boldine (5), 15 and 16 surpassed significantly the inhibition expressed by 1 on Con A-induced proliferative response. The effect was equal to the inhibition determined for mitomycin C (Mit C) with both mitogens. In contrast to all others analogues, thaliporphine (2) stimulated splenocyte proliferation in both assays. Antibody response against sheep red blood cells (SRBC) was lowered most strongly by cataline (6), 7-methyldehydroglaucine (10) and 16.
Assuntos
Antioxidantes/farmacologia , Aporfinas/farmacologia , Baço/citologia , Animais , Formação de Anticorpos/efeitos dos fármacos , Antioxidantes/química , Aporfinas/química , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Concanavalina A/farmacologia , Eritrócitos/imunologia , Técnicas In Vitro , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos ICR , Ovinos/imunologia , Baço/efeitos dos fármacosRESUMO
The constantly increasing number of substances with adjuvant activity outpaces the elucidation of their mode of action. This problem is of great importance as the immunomodulatory action of an adjuvant is time- and route-dependent, which implies that administration at a different moment or site may result in a reduced immune response. In the present work the possibility to achieve dual effect (stimulatory or inhibitory) is regarded in the light of the complement system. The object of the study is a preparation obtained by lysozyme digestion of Nocardia opaca cell walls (NLD). According to the results, the administration of NLD to mice (i.p. at a daily dose of 0.5 mg kg-1) during 3 days prior to the antigen resulted in an inhibition of serum antibody level against sheep red blood cells (SRBC) and lipopolysaccharide (LPS). At the same time, the preparation stimulated the antibody response to SRBC if it was applied after the antigen. The ability of NLD to ensure protection against experimental infection with Klebsiella pneumoniae was comparatively studied in complement-normal mice (strain ICR) and in C5-deficient mice (strain DBA/2). Firstly, it was established that complement-deficient mice were more resistant to infection than complement-normal. Secondly, the preparation expressed a protective effect in C5-deficient animals; nevertheless the inoculation was done s.c. or i.v. The departure of the infection depended on the rate of opsonization of K. pneumoniae. Under certain conditions NLD can provoke excessive C3 activation, which might aggravate the course of the infection. The preparation augmented the host response to second challenge with K. pneumoniae of complement-normal and C5-deficient mice.
Assuntos
Adjuvantes Imunológicos , Complemento C5/deficiência , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae , Muramidase/farmacologia , Nocardia/enzimologia , Animais , Anticorpos Antibacterianos/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos DBA , Camundongos Endogâmicos ICR , Valores de ReferênciaRESUMO
Three new piperidine alkaloids were isolated from stems, leaves and flowers of Lobelia laxiflora L. (Campanulaceae). The structures of racem. cis-8,10-diethyl-3,4-dehydrolobelidiol (1), racem. trans-8-ethyl-10-phenyl-3,4-dehydrolobelidiol (2) and racem. cis-8-ethyl-10-phenyl-3, 4-dehydrolobelidiol (3) were established by spectral analyses. The residues obtained from the ethanol extracts from stems (S), leaves (L), and flowers (F) were applied in carrageenan (Car)- and cobra venom (CV)-induced acute inflammation in mice. A suppression of paw edema formation at a dose of 100 mg kg-1 was established. In this study the antiinflammatory potential of Lobelia l. was regarded in connection with the complement system. The sequential activation and assembly into functional units of complement components can proceed via two different pathways, named classical (CP) and alternative (AP). The ability of the residues, nonalkaloid fractions, alkaloid fractions and the three alkaloids at a concentration from 0.125 to 1.0 mg ml-1 to inhibit complement activation and thus to prevent inflammatory process was estimated in vitro in human serum via both pathways. All of them inhibited complement activity with a predominant action on CP.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inflamação/tratamento farmacológico , Magnoliopsida , Extratos Vegetais/farmacologia , Plantas Medicinais , Alcaloides/análise , Alcaloides/química , Alcaloides/farmacologia , Animais , Carragenina , Ativação do Complemento/efeitos dos fármacos , Venenos Elapídicos , Humanos , Inflamação/induzido quimicamente , Camundongos , Extratos Vegetais/química , Folhas de Planta , Caules de PlantaRESUMO
The ability of aporphinoid alkaloid oxoglaucine to influence T- and B-cell immune response was studied in mice models. The substance inhibited in vitro mitogen-induced lymphocyte proliferation and suppressed antibody response to sheep red blood cells (SRBC) and lipopolysaccharide (LPS) in vivo effectively. The action depended on the relative timing of antigen and oxoglaucine administration. The substance manifested stimulatory effect in popliteal lymph node (PLN) reaction and LPS-induced B-cell activation. In the chronic inflammatory model of adjuvant arthritis oxoglaucine exhibited stimulatory or suppressive action related to the kinetics of the process. At low doses (1 or 2 mg kg-1) oxoglaucine improved the outcome of Klebsiella pneumoniae infection, while at higher doses (10 or 20 mg kg-1) the substance caused an impairment of host resistance to infectious agent. The comparison with cyclophosphamide in some tests showed that oxoglaucine was effective in manifold lower doses. In conclusion, oxoglaucine exerted immunomodulatory effects in vivo in a dose-dependent and protocol-dependent manner. Yet, its overall action might be attributed to the different sensitivity of the cells involved in the developing immune response.
Assuntos
Adjuvantes Imunológicos/farmacologia , Formação de Anticorpos/efeitos dos fármacos , Aporfinas/farmacologia , Animais , Artrite Experimental/prevenção & controle , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Eritrócitos/imunologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/prevenção & controle , Klebsiella pneumoniae , Lipopolissacarídeos/imunologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
Several phenolic constituents of propolis and their synthetic analogs were derivatized with L-lysine. The ability of these complexes to alter complement activity was estimated in vitro in human serum. The influence of selected complexes on C3 hemolytic activity via classical pathway (CP) and alternative pathway (AP) and on zymosan-induced AP activation was determined. The results suppose that the anticomplement effect of the complexes might be related to the interaction with C3 complement component.
Assuntos
Proteínas Inativadoras do Complemento/farmacologia , Via Alternativa do Complemento/efeitos dos fármacos , Via Clássica do Complemento/efeitos dos fármacos , Flavanonas , Hemólise/efeitos dos fármacos , Lisina , Fenóis/farmacologia , Própole/farmacologia , Ésteres , Flavonoides/farmacologia , Humanos , Relação Estrutura-Atividade , Zimosan/farmacologiaRESUMO
The immunoregulatory activity of aporphinoid alkaloid oxoglaucine was studied in delayed-type hypersensitivity (DTH) reaction and Klebsiella pneumoniae infection in normal and immunosuppressed mice. The alkaloid enhanced DTH reaction when applied during the developing phase and abolished the inhibitory action of cyclophosphamide. Oxoglaucine possessed a restorative effect in K. pneumoniae infection in immunosuppressed mice in combination with indomethacin, prednisolone or artemisinin, as evaluated by the number of survivors and mean survival time. These data suggest that oxoglaucine affects selected lymphocyte clones responsible for antiinfectious host resistance. Its use as a second agent in combination with another immunosuppressant might enable reduction in the dosage or time of application.