RESUMO
Asthma is a chronic respiratory disease characterized by airway inflammation and airway hyperresponsiveness (AHR). One strategy to treat allergic diseases is the development of new drugs. Flavonoids are compounds derived from plants and are known to have antiallergic, anti-inflammatory, and antioxidant properties. To investigate whether the flavonoid kaempferol glycoside 3-O-[beta-d-glycopiranosil-(1-->6)-alpha-l-ramnopiranosil]-7-O-alpha-l-ramnopiranosil-kaempferol (GRRK) would be capable of modulating allergic airway disease (AAD) either as a preventive (GRRK P) or curative (GRRK C) treatment in an experimental model of asthma. At weekly intervals, BALB/c mice were subcutaneously (sc) sensitized twice with ovalbumin (OVA)/alum and challenged twice with OVA administered intranasally. To evaluate any preventive effect, GRRK was administered 1h (hour) before each OVA-sensitization and challenge, while to analyze the curative effect, mice were first sensitized with OVA, followed by GRRK given at day 18 through 21. The onset of AAD was evaluated 24h after the last OVA challenge. Both treatments resulted in a dose-dependent reduction in total leukocyte and eosinophil counts in the bronchoalveolar lavage fluid (BAL). GRRK also decreased CD4(+), B220(+), MHC class II and CD40 molecule expressions in BAL cells. Histology and lung mechanic showed that GRRK suppressed mucus production and ameliorated the AHR induced by OVA challenge. Furthermore, GRRK impaired Th2 cytokine production (IL-5 and IL-13) and did not induce a Th1 pattern of inflammation. These findings demonstrate that GRRK treatment before or after established allergic lung disease down-regulates key asthmatic features. Therefore, GRRK has a potential clinical use for the treatment of allergic asthma.
Assuntos
Asma/tratamento farmacológico , Dissacarídeos/administração & dosagem , Eosinófilos/efeitos dos fármacos , Glicosídeos/administração & dosagem , Quempferóis/administração & dosagem , Leucócitos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Animais , Antígenos CD/biossíntese , Antígenos CD/genética , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Dissacarídeos/química , Dissacarídeos/isolamento & purificação , Eosinófilos/patologia , Feminino , Glicosídeos/química , Glicosídeos/isolamento & purificação , Antígenos de Histocompatibilidade Classe II/biossíntese , Antígenos de Histocompatibilidade Classe II/genética , Interleucina-13/metabolismo , Interleucina-5/metabolismo , Quempferóis/química , Quempferóis/isolamento & purificação , Leucócitos/patologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Muco/metabolismo , Ovalbumina/imunologia , Células Th2/imunologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The bee pollen is used in folk medicine to alleviate allergic reactions. The bee pollen phenolic extract (BPPE) consists in phenolic compounds (flavonoids) from plants picked by Apis mellifera bee. AIM OF THIS STUDY: Here we evaluated the anti-allergic property of the BPPE and the flavonoid myricetin (MYR) in murine model of ovalbumin (OVA)-induced allergy. MATERIALS AND METHODS: The study focused on the BPPE or myricetin treatment of OVA-sensitized BALB/c mice and their effects on the IgE and IgG1 production, pulmonary cell migration, eosinophil peroxidase (EPO) activity and anaphylactic shock reaction. RESULTS: The BPPE treatment (200mg/kg) showed inhibition of the paw edema, IgE and IgG(1) OVA-specific production, leukocyte migration to the bronchoalveolar lavage (BAL) and EPO activity in lungs. In addition, BPPE treatment showed partial protection on the anaphylactic shock reaction induced by OVA. Treatment with myricetin (5 mg/kg) also inhibited pulmonary cell migration and IgE and IgG(1) OVA-specific production. CONCLUSIONS: These results support the hypothesis the myricetin is one of the flavonoids of BPPE responsible for the anti-allergic effect and a potential tool to treat allergies.
Assuntos
Antialérgicos/farmacologia , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Pólen/química , Anafilaxia/tratamento farmacológico , Anafilaxia/imunologia , Animais , Antialérgicos/isolamento & purificação , Abelhas , Líquido da Lavagem Broncoalveolar/imunologia , Movimento Celular/imunologia , Modelos Animais de Doenças , Peroxidase de Eosinófilo/efeitos dos fármacos , Peroxidase de Eosinófilo/metabolismo , Feminino , Flavonoides/isolamento & purificação , Imunoglobulina E/efeitos dos fármacos , Imunoglobulina E/imunologia , Imunoglobulina G/efeitos dos fármacos , Imunoglobulina G/imunologia , Leucócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Ratos , Ratos WistarRESUMO
Warifteine is a bisbenzylisoquinoline alkaloid isolated from the Cissampelos sympodialis Eichl (Menispermaceae). This plant is used in the folk medicine for the treatment of airway respiratory diseases. A murine model of immediate allergic reaction was used to evaluate warifteine treatment in the IgE production, leukocyte activation, thermal hyperalgesia, mast cell degranulation and scratching behavior. BALB/c mice treated with warifteine (0.4-10 mg/Kg) 1 h before OVA sensitization reduced OVA induced paw edema as well as the OVA-specific IgE serum titers as compared with non-treated and OVA-sensitized animals. Warifteine also reduced the mice death evoked by IgE-dependent anaphylactic shock reaction at 30 min after intravenous OVA challenge. To assess the effect of warifteine treatment on T cell proliferative response, spleen cells from warifteine treated or non-treated and OVA-sensitized animals were evaluated. Spleen cells from warifteine treated animals (2.0 mg/kg) did not proliferate following OVA stimulation as compared with spleen cell cultures from non-treated animals. This response may be related with the increase of NO production as observed in peritoneal macrophage cultures treated with warifteine. Thermal hyperalgesia evoked by IgE or histamine/5-hydroxytryptamine challenge was inhibited on rats at dose of 4.0 mg/kg. Warifteine treatment (0.6 or 6.0 microg/ml) also decreased the IgEalphaDNP-BSA sensitized mast degranulation after DNP-BSA challenge measured by histamine release. In addition, compound 48/80-induced scratching behavior was also sensitive to warifteine treatment. These results demonstrate for the first time that warifteine treatment reduced the allergy-associated responses.
Assuntos
Alcaloides/uso terapêutico , Hiperalgesia/tratamento farmacológico , Hipersensibilidade Imediata/tratamento farmacológico , Linfócitos T/imunologia , Alcaloides/administração & dosagem , Alcaloides/isolamento & purificação , Anafilaxia/tratamento farmacológico , Anafilaxia/imunologia , Animais , Degranulação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Liberação de Histamina/efeitos dos fármacos , Hiperalgesia/imunologia , Imunoglobulina E/sangue , Ativação Linfocitária/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Ovalbumina/imunologia , Ratos , Ratos WistarRESUMO
The murine model of OVA-induced immediate allergic reaction was used to evaluate the effectiveness of intraperitoneal sub-acute treatment with the leaf hydroalcoholic extract of Cissampelos sympodialis (AFL) in the anaphylactic shock reaction, IgE production and the background proliferative response. BALB/c mice treated with AFL ranging from 200 to 400 mg/kg/day for 5 days before and during OVA-sensitization strongly reduced the animal death and promoted reduction in total and OVA-specific serum IgE level. Spleen cells from AFL-treated sensitized animals showed a decreased proliferative background response when compared with non-sensitized animals. These results demonstrated that sub-acute intraperitoneal treatment with Cissampelos sympodialis extract has an anti-allergic effect.
RESUMO
The murine model of ovalbumin (OVA)-induced allergy was used to evaluate the effectiveness of oral treatment with the leaf extract of Cissampelos sympodialis Eichl. (Menispermaceae) (CS) in the modulation of immunoglobulin E (IgE) production and T cell activation. CS treatment with doses ranging from 200 to 600 mg/Kg/day for 15 days before and during OVA-sensitization promoted reduction in total and OVA-specific serum IgE. CS at 400 or 600 mg/Kg/day also reduced paw edema induced by local OVA challenge. Daily intake of up to 600 mg/Kg of oral CS by BALB/c mice did not reduce weight gain, which is indicative of a lack of systemic toxicity. To assess the effect of CS treatment on T cell proliferative response to stimuli in vitro, the mitogenic response of spleen cells of treated and control animals were evaluated. Cells from CS-treated animals showed an elevated background proliferative response to concanavalin-A (Con-A) when compared to those from control animals. Oral intake of CS increased the in vitro production of IFN-gamma and IL-10 by Con-A stimulated cells. Mice treated with 200 mg/Kg/day CS showed increasing levels of IFN-gamma. These results show that oral treatment with Cissampelos sympodialis extract has an immunomodulatory effect, reducing allergy-associated responses possibly by a preferential activation of Th1-type cytokines.
Assuntos
Cissampelos , Citocinas/biossíntese , Imunoglobulina E/sangue , Ovalbumina/toxicidade , Células Th1/efeitos dos fármacos , Administração Oral , Animais , Edema/sangue , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Imunoglobulina E/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Ratos , Ratos Wistar , Células Th1/metabolismoRESUMO
Cissampelos sympodialis Eichl species are used in folk medicine for the treatment of asthma, arthritis and rheumatism. In the present study, we investigated the immunomodulatory effect of an aqueous fraction of a 70 percent (v/v) ethanol extract of C. sympodialis leaves on B lymphocyte function. The hydroalcoholic extract inhibited the in vitro proliferative response of resting B cells induced by LPS (IC50 = 17.2 æg/ml), anti-delta-dextran (IC50 = 13.9 æg/ml) and anti-IgM (IC50 = 24.3 æg/ml) but did not affect the anti-MHC class II antibody-stimulated proliferative response of B cell blasts obtained by stimulation with IL-4 and anti-IgM. Incubation with the hydroalcoholic extract used at 50 æg/ml induced a 700 percent increase in intracellular cAMP levels. IgM secretion by resting B cells (obtained from normal mice) and polyclonally activated B cells (obtained from Trypanosoma cruzi-infected animals) was inhibited by the hydroalcoholic extract. The latter were more sensitive to the hydroalcoholic extract since 6.5 æg/ml induced a 20 percent inhibition in the response of cells from normal mice while it inhibited the response of B cells from infected animals by 75 percent. The present data indicate that the alcoholic extract of C. sympodialis inhibited B cell function through an increase in intracellular cAMP levels. The finding that the hydroalcoholic extract inhibited immunoglobulin secretion suggests a therapeutic use for the extract from C. sympodialis in conditions associated with unregulated B cell function and enhanced immunoglobulin secretion. Finally, the inhibitory effect of the hydroalcoholic extract on B cells may indicate an anti-inflammatory effect of this extract.
Assuntos
Animais , Masculino , Feminino , Camundongos , Anti-Inflamatórios , Linfócitos B , Etanol , Extratos Vegetais , Trypanosoma cruzi , Anti-Inflamatórios , Linfócitos B , Células Cultivadas , AMP Cíclico , Ensaio de Imunoadsorção Enzimática , Etanol , Imunoglobulinas , Lipopolissacarídeos , Camundongos Endogâmicos BALB C , Extratos VegetaisRESUMO
Cissampelos sympodialis Eichl species are used in folk medicine for the treatment of asthma, arthritis and rheumatism. In the present study, we investigated the immunomodulatory effect of an aqueous fraction of a 70% (v/v) ethanol extract of C. sympodialis leaves on B lymphocyte function. The hydroalcoholic extract inhibited the in vitro proliferative response of resting B cells induced by LPS (IC50 = 17.2 g/ml), anti-delta-dextran (IC50 = 13.9 g/ml) and anti-IgM (IC50 = 24.3 g/ml) but did not affect the anti-MHC class II antibody-stimulated proliferative response of B cell blasts obtained by stimulation with IL-4 and anti-IgM. Incubation with the hydroalcoholic extract used at 50 g/ml induced a 700% increase in intracellular cAMP levels. IgM secretion by resting B cells (obtained from normal mice) and polyclonally activated B cells (obtained from Trypanosoma cruzi-infected animals) was inhibited by the hydroalcoholic extract. The latter were more sensitive to the hydroalcoholic extract since 6.5 g/ml induced a 20% inhibition in the response of cells from normal mice while it inhibited the response of B cells from infected animals by 75%. The present data indicate that the alcoholic extract of C. sympodialis inhibited B cell function through an increase in intracellular cAMP levels. The finding that the hydroalcoholic extract inhibited immunoglobulin secretion suggests a therapeutic use for the extract from C. sympodialis in conditions associated with unregulated B cell function and enhanced immunoglobulin secretion. Finally, the inhibitory effect of the hydroalcoholic extract on B cells may indicate an anti-inflammatory effect of this extract.
Assuntos
Anti-Inflamatórios/farmacologia , Linfócitos B/efeitos dos fármacos , Cissampelos/química , Etanol/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Linfócitos B/imunologia , Linfócitos B/parasitologia , Células Cultivadas , AMP Cíclico/análise , Ensaio de Imunoadsorção Enzimática , Etanol/isolamento & purificação , Feminino , Imunoglobulinas/biossíntese , Imunoglobulinas/efeitos dos fármacos , Imunoglobulinas/imunologia , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Trypanosoma cruziRESUMO
The aqueous fraction of the ethanolic extract (AFL) of Cissampelos sympodialis Eichl (Menispermaceae), popularly known as milona, has been shown to have both immunosuppressive and anti-inflammatory effects. In the present study we investigated the modulation of macrophage antimicrobicidal activity by in vitro treatment with the extract from C. sympodialis. Normal and thioglycolate-elicited mouse peritoneal macrophages were infected in vitro with the protozoan Trypanosoma cruzi DM28c clone. We observed that the AFL (used at doses ranging from 13 to 100 microg/ml) increased T. cruzi growth and induced a 75% reduction in nitric oxide production. This inhibition could be mediated by the stimulation of macrophage interleukin-10 (IL-10) secretion since the in vitro treatment with the AFL stimulated IL-10 production by T. cruzi-infected macrophages. These results suggest that the anti-inflammatory effect of the AFL from C. sympodialis could be, at least in part, mediated by the inhibition of macrophage functions and that the inhibition of macrophage microbicidal activity induced by the C. sympodialis extract may be mediated by the decrease in macrophage function mediated by interleukin-10 production.
Assuntos
Anti-Inflamatórios/farmacologia , Cissampelos/química , Interleucina-10/biossíntese , Macrófagos Peritoneais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Células Cultivadas , Feminino , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Macrófagos Peritoneais/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/biossíntese , Folhas de Planta , Trypanosoma cruzi/crescimento & desenvolvimentoRESUMO
The aqueous fraction of the ethanolic extract (AFL) of Cissampelos sympodialis Eichl (Menispermaceae), popularly known as milona, has been shown to have both immunosuppressive and anti-inflammatory effects. In the present study we investigated the modulation of macrophage antimicrobicidal activity by in vitro treatment with the extract from C. sympodialis. Normal and thioglycolate-elicited mouse peritoneal macrophages were infected in vitro with the protozoan Trypanosoma cruzi DM28c clone. We observed that the AFL (used at doses ranging from 13 to 100 æg/ml) increased T. cruzi growth and induced a 75 percent reduction in nitric oxide production. This inhibition could be mediated by the stimulation of macrophage interleukin-10 (IL-10) secretion since the in vitro treatment with the AFL stimulated IL-10 production by T. cruzi-infected macrophages. These results suggest that the anti-inflammatory effect of the AFL from C. sympodialis could be, at least in part, mediated by the inhibition of macrophage functions and that the inhibition of macrophage microbicidal activity induced by the C. sympodialis extract may be mediated by the decrease in macrophage function mediated by interleukin-10 production
Assuntos
Animais , Masculino , Feminino , Camundongos , Anti-Inflamatórios , Cissampelos/química , Interleucina-10 , Macrófagos Peritoneais , Extratos Vegetais , Trypanosoma cruzi , Células Cultivadas , Ativação de Macrófagos , Macrófagos Peritoneais , Camundongos Endogâmicos BALB C , Óxido Nítrico , Folhas de Planta , Trypanosoma cruziRESUMO
Curatella americana L. (Dilleneaceae) popularly known as 'cajueiro-bravo' and 'sambaiba' is used in Brazilian folk medicine for the treatment of inflammation and ulcer. The anti-inflammatory and analgesic tests were conducted with the hydroalcoholic extract (HAE) of the bark of the plant. The HAE inhibited mouse ear oedema induced by o-tetradecanoyl phorbol acetate (TPA) and by capsaicin. While the ID50 values obtained for the HAE against these two irritants were 40.8 +/- 1.7 and 30 +/- 1.2 mg/kg i.p. (mean +/- S.E.M., n = 6), respectively, the corresponding value for carrageenan induced paw oedema (3 h) was 21.8 +/- 2.1 mg/kg, i.p., n = 6. In the established adjuvant-induced arthritis model, the HAE significantly inhibited the oedema in daily doses of 50 mg/kg, i.p. (n = 10). The HAE also inhibited acetic acid-induced writhing (ID50 23.2 +/- 0.8 mg/kg, i.p., n = 6) and the formalin-induced late phase paw licking response (ID50 11.9 +/- 1.2 mg/kg, i.p., n = 10) in the mice. However, the HAE was inactive in the formalin-induced initial paw licking response in mice or heat induced tail flick response in rats. The HAE has shown both anti-inflammatory and peripheral analgesic activities when administrated in the mouse by the intraperitoneal route in doses which are at least 12 times lower than its LD50 dose of 647 mg/kg, i.p.