RESUMO
The bioactive components of Canavalia lineata (Thunb.) DC pods were investigated using bioactivity-guided isolation, and the chemical structures of flavonoids 1-3, isoflavonoid derivatives 4-11, and phenolic compounds 12 and 13 were identified by comparing NMR, MS, and CD spectral data with previously reported spectroscopic data. Compounds 1-13 were evaluated for their anti-inflammatory effects on LPS-stimulated RAW264.7 macrophages. Among these compounds, the isoflavonoid derivative cajanin (7) exhibited the most potent anti-inflammatory activity (IC50 of NO = 19.38 ± 0.05 µM; IC50 of IL-6 = 7.78 ± 0.04 µM; IC50 of TNF-α = 26.82 ± 0.11 µM), exerting its anti-inflammatory effects by suppressing the activation and nuclear translocation of the transcription factor NF-κB by phosphorylating IκB and p65. These results suggested that cajanin (7) may be a potential candidate for improving the treatment of inflammatory diseases.
Assuntos
Canavalia , Lipopolissacarídeos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Macrófagos , Camundongos , NF-kappa B/farmacologia , Óxido Nítrico/farmacologia , Células RAW 264.7RESUMO
Peucedanum japonicum Thunberg (PJT) has been used in traditional medicine to treat colds, coughs, fevers, and other inflammatory diseases. The goal of this study was to investigate whether 3'-isovaleryl-4'-senecioylkhellactone (IVSK) from PJT has anti-inflammatory effects on lung epithelial cells. The anti-inflammatory effects of IVSK were evaluated using phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells and regular human lung epithelial cells as a reference. IVSK reduced the secretion of the inflammatory mediators interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1), and the mRNA expression of IL-6, IL-8, MCP-1, and IL-1ß. Additionally, it inhibited the phosphorylation of IκB kinase (IKK), p65, Iκ-Bα, and mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK in A549 cells stimulated with PMA. Moreover, the binding affinity of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) was significantly reduced in the luciferase assay, while nuclear translocation was markedly inhibited by IVSK in the immunocytochemistry. These findings indicate that IVSK can protect against inflammation through the AP-1 and NF-κB pathway and could possibly be used as a lead compound for the treatment of inflammatory lung diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Apiaceae/metabolismo , Células Epiteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Ésteres de Forbol/farmacologia , Células A549/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Quinase I-kappa B/metabolismo , Inflamação , Mediadores da Inflamação/metabolismo , Interleucina-1beta , Interleucina-8 , Proteínas Quinases Ativadas por Mitógeno/metabolismo , RNA Mensageiro/metabolismo , Fator de Transcrição AP-1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
3,4,5Trihydroxycinnamic acid (THCA) exhibits antiinflammatory activity in acute or chronic inflammatory disorders, such as acute lung injury and asthma. The present study investigated the antiinflammatory activity of THCA in a tumor necrosis factorα/interferonγ (TI) mixturestimulated human keratinocyte cell line. The results of ELISA and reverse transcriptionquantitative PCR revealed that THCA reduced the secretion and mRNA expression levels of interleukin (IL)6; IL8; thymus and activationregulated chemokine; macrophagederived chemokine; regulated upon activation, normal T cell expressed and secreted; and monocyte chemoattractant protein1 in TI mixturestimulated HaCaT cells. In addition, the results of western blot analysis demonstrated that THCA exerted inhibitory activity on the activation of AKT, ERK and nuclear factorκB in TI mixturestimulated HaCaT cells. Furthermore, THCA upregulated the expression levels of heme oxygenase1 and NAD(P)H:quinone oxidoreductase 1, and the activation of nuclear factor erythroid 2related factor 2 in HaCaT cells. These results demonstrated that THCA may exhibit antiinflammatory activity in activated HaCaT cells.
Assuntos
Anti-Inflamatórios/farmacologia , Cinamatos/farmacologia , Interferon gama/farmacologia , Queratinócitos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Proteínas ADAM/genética , Proteínas ADAM/metabolismo , Quimiocina CCL17/genética , Quimiocina CCL17/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CCL5/genética , Quimiocina CCL5/metabolismo , Células HaCaT , Heme Oxigenase-1/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição RelA/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa japonica Thunb., as an herbal medicine has been used for the treatment of inflammatory diseases in China and Korea. MATERIALS AND METHODS: Ultra performance liquid chromatography-photodiode array-quadrupole time-of-flight mass spectrometer (UPLC-PDA-QTof MS) was used to detect the major phenylethanoid glycosides in the C. japonica extract. BALB/c mice were intraperitoneally sensitized by ovalbumin (OVA) (on days 0 and 7) and challenged by OVA aerosol (on days 11-13) to induce airway inflammatory response. The mice were also administered with C. japonica Thunb. (CJT) (20 and 40 mg/kg Per oral) on days 9-13. CJT pretreatment was conducted in lipopolysaccharide (LPS)-stimulated RAW264.7 or phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells. RESULTS: CJT administration significantly reduced the secretion of Th2 cytokines, TNF-α, IL-6, immunoglobulin E (IgE) and histamine, and the recruitment of eosinophils in an OVA-exposed mice. In histological analyses, the amelioration of inflammatory cell influx and mucus secretion were observed with CJT. The OVA-induced airway hyperresponsiveness (AHR), iNOS expression and NF-κB activation were effectively suppressed by CJT administration. In addition, CJT led to the upregulation of HO-1 expression. In an in vitro study, CJT pretreatment suppressed the LPS-induced TNF-α secretion in RAW264.7 cells and attenuated the PMA-induced IL-6, IL-8 and MCP-1 secretion in A549 cells. These effects were accompanied by downregulated NF-κB phosphorylation and by upregulated HO-1 expression. CONCLUSION: These results suggested that CJT has protective activity against OVA-induced airway inflammation via downregulation of NF-κB activation and upregulation of HO-1, suggesting that CJT has preventive potential for the development of allergic asthma.
Assuntos
Antiasmáticos/farmacologia , Anti-Inflamatórios/farmacologia , Asma/prevenção & controle , Hiper-Reatividade Brônquica/prevenção & controle , Callicarpa , Heme Oxigenase-1/metabolismo , Pulmão/efeitos dos fármacos , Proteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Células A549 , Animais , Antiasmáticos/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Asma/induzido quimicamente , Asma/enzimologia , Asma/fisiopatologia , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/enzimologia , Hiper-Reatividade Brônquica/fisiopatologia , Broncoconstrição/efeitos dos fármacos , Callicarpa/química , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Pulmão/enzimologia , Pulmão/fisiopatologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , Transdução de Sinais , Regulação para CimaRESUMO
A number of species of the genus Trichilia (Meliaceae) exhibit anti-inflammatory effects. However, the effect of Trichilia martiana C. DC. (TM) on lipopolysaccharide (LPS)-induced inflammation has not, to the best of our knowledge, yet been determined. Therefore, in the present study, the antiinflammatory effect of TM on LPS-stimulated RAW264.7 macrophages was evaluated. The ethanol extract of TM (TMEE) significantly inhibited LPS-induced nitric oxide (NO), prostaglandin 2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). TMEE also reduced the levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß and IL-6. The upregulation of mitogen-activated protein kinases (MAPKs) and NF-κB activation was revealed to be downregulated following TMEE pretreatment. Furthermore, TMEE was indicated to lead to the nucleus translocation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1). In H292 airway epithelial cells, the pretreatment of TMEE significantly downregulated the production of LPS-stimulated IL-1ß, and TMEE was indicated to increase the expression of HO-1. In animal models exhibiting LPS-induced acute lung injury (ALI), treatment with TMEE reduced the levels of macrophages influx and TNF-α production in the bronchoalveolar lavage fluid (BALF) of ALI mice. Additionally, TMEE significantly downregulated the activation of ERK, JNK and IκB, and upregulated the expression of HO-1 in the lungs of ALI mice. In conclusion, the results of the current study demonstrated that TMEE could exert a regulatory role in the prevention or treatment of the endotoxin-mediated inflammatory response.
Assuntos
Anti-Inflamatórios/farmacologia , Células Epiteliais/efeitos dos fármacos , Lipopolissacarídeos/efeitos adversos , Macrófagos/efeitos dos fármacos , Meliaceae/química , Extratos Vegetais/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Ciclo-Oxigenase 2 , Citocinas/metabolismo , Modelos Animais de Doenças , Heme Oxigenase-1 , Inflamação/tratamento farmacológico , Interleucina-1beta , Interleucina-6 , Pulmão , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Prostaglandinas , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
There is an increasing interest in natural products and their derivatives with therapeutic benefits and less side effects compared to steroid therapy. Benzofuran derivatives display biological effects including anti-inflammatory effects. The present study aims to investigate whether (3-(7-methoxy-2-p-tolyl benzofuran-5-yl) propan-1-ol) (DK-1108), new synthetic benzofuran compound exerts anti-asthmatic effects in vitro and in vivo. DK-1108 strongly reduced the production of inflammatory mediators, cytokines and chemokines in RAW264.7 and A549 cells. DK-1108 significantly regulated the levels of AKT/MAPKs/c-Jun activation, AP-1 luciferase activity and ICAM-1 expression. Furthermore, DK-1108 effectively suppressed the adhesion of A549 and EOL-1 cells. In OVA-induced asthmatic mice, DK-1108 decreased the levels of IL-5/IL-13/IgE production, eosinophils/macrophages influx, ICAM-1/MCP-1 expression, mucus secretion and airway hyperresponsiveness (AHR). These effects of DK-1108 were accompanied by downregulation of MAPKs activation. Therefore, we suggest that DK-1108 exerts protective effect against airway inflammation and mucus overproduction, and therefore could be valuable therapeutic agent for treatment in asthma.
Assuntos
Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Benzofuranos/uso terapêutico , Ovalbumina/toxicidade , Hipersensibilidade Respiratória/tratamento farmacológico , Acetato de Tetradecanoilforbol/análogos & derivados , Células A549 , Animais , Antiasmáticos/química , Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Asma/induzido quimicamente , Asma/metabolismo , Benzofuranos/química , Benzofuranos/farmacologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Células RAW 264.7 , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/metabolismo , Acetato de Tetradecanoilforbol/toxicidadeRESUMO
3,4,5-Trihydroxycinnamic acid (THCA) has been reported to possess anti-inflammatory activity. However, the effect of THCA for treating allergic asthma was unknown. Therefore, in the present study, the anti-asthmatic effects of THCA were studied in both in vitro and in vivo studies. In phorbol 12-myristate 13-acetate (PMA)-stimulated A549 airway epithelial cells, THCA pretreatment decreased the mRNA expression and secretion of interleukin (IL)-8, monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecules 1 (ICAM-1), and reduced the mRNA expression of matrix metalloproteinase 9 (MMP-9). THCA also inhibited PMA-induced protein kinase B (AKT), mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activation in A549 cells. In lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, THCA pretreatment suppressed the mRNA expression of ICAM-1 and MMP-9. In addition, THCA suppressed the adhesion of EOL and A549 cells. In ovalbumin (OVA)-administered asthmatic mice, THCA exerted inhibitory activity on IL-5, IL-13, and MCP-1 in bronchoalveolar lavage fluid (BALF) and on OVA-specific immunoglobulin E (IgE) in serum. THCA attenuated the numbers of inflammatory cells in BALF and the influx of inflammatory cell in lung tissues. Furthermore, THCA downregulated the levels of inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2), and leukotriene B4 (LTB4) expression, mucus production and CREB phosphorylation as well as Penh value. These effects were accompanied by suppression of AKT, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and NF-κB activation. Therefore, the results of the current study suggest that THCA may be a valuable adjuvant or therapeutic in the prevention or treatment of allergic asthma.