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1.
Int J Mol Sci ; 23(23)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36499236

RESUMO

Methyl p-coumarate (methyl p-hydroxycinnamate) (MH) is a natural compound found in a variety of plants. In the present study, we evaluated the ameliorative effects of MH on airway inflammation in an experimental model of allergic asthma (AA). In this in vitro study, MH was found to exert anti-inflammatory activity on PMA-stimulated A549 airway epithelial cells by suppressing the secretion of IL-6, IL-8, MCP-1, and ICAM-1. In addition, MH exerted an inhibitory effect not only on NF-κB (p-NF-κB and p-IκB) and AP-1 (p-c-Fos and p-c-Jun) activation but also on A549 cell and EOL-1 cell (eosinophil cell lines) adhesion. In LPS-stimulated RAW264.7 macrophages, MH had an inhibitory effect on TNF-α, IL-1ß, IL-6, and MCP-1. The results from in vivo study revealed that the increases in eosinophils/Th2 cytokines/MCP-1 in the bronchoalveolar lavage fluid (BALF) and IgE in the serum of OVA-induced mice with AA were effectively inhibited by MH administration. MH also exerted a reductive effect on the immune cell influx, mucus secretion, and iNOS/COX-2 expression in the lungs of mice with AA. The effects of MH were accompanied by the inactivation of NF-κB. Collectively, the findings of the present study indicated that MH attenuates airway inflammation in mice with AA, suggesting its potential as an adjuvant in asthma therapy.


Assuntos
Asma , NF-kappa B , Animais , Camundongos , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6 , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Ovalbumina
2.
J Ginseng Res ; 46(3): 496-504, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35600779

RESUMO

Background: Cigarette smoke (CS) is considered a principal cause of chronic obstructive pulmonary disease (COPD) and is associated with mucus hypersecretion and airway inflammation. Ginsenoside compound K (CK), a product of ginsenoside metabolism, has various biological activities. Studies on the effects of CK for the treatment of COPD and mucus hypersecretion, including the underlying signaling mechanism, have not yet been conducted. Methods: To study the protective effects and molecular mechanism of CK, phorbol 12-myristate 13-acetate (PMA)-induced human airway epithelial (NCI-H292) cells were used as a cellular model of airway inflammation. An experimental mouse COPD model was also established via CS inhalation and intranasal administration of lipopolysaccharide. Mucin 5AC (MUC5AC), monocyte chemoattractant protein-1, tumor necrosis factor-α (TNF-α), and interleukin-6 secretion, as well as elastase activity and reactive oxygen species production, were determined through enzyme-linked immunosorbent assay. Inflammatory cell influx and mucus secretion in mouse lung tissues were estimated using hematoxylin and eosin and periodic acid-schiff staining, respectively. PKCδ and its downstream signaling molecules were analyzed via western blotting. Results: CK prevented the secretion of MUC5AC and TNF-α in PMA-stimulated NCI-H292 cells and exhibited a protective effect in COPD mice via the suppression of inflammatory mediators and mucus secretion. These effects were accompanied by an inactivation of PKCδ and related signaling in vitro and in vivo. Conclusion: CK suppressed pulmonary inflammation and mucus secretion in COPD mouse model through PKC regulation, highlighting the compound's potential as a useful adjuvant in the prevention and treatment of COPD.

3.
Phytomedicine ; 96: 153848, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34785110

RESUMO

BACKGROUND: Since long-term or high-dose use of COPD medication causes adverse effects in patients with COPD, more effective and safer ways to manage COPD symptoms are required. Daphne kiusiana Miquel is a medicinal plant, but its anti-COPD efficacy was little studied. PURPOSE: We investigated the anti-COPD activity and molecular mechanism of action of active compounds isolated from D. kiusiana to find drug candidates for COPD. METHODS: We isolated seven compounds (1-7) in an ethyl acetate (EtOAc) fraction from D. kiusiana, and determined that seven compounds effectively control the inflammatory responsiveness in both PMA-stimulated lung epithelial cells (in vitro) and/or in COPD model mice using cigarette smoke- and lipopolysaccharides-exposed animals in vivo. RESULTS: We show that the ethyl acetate (EtOAc) fraction from D. kiusiana. suppresses inflammatory response in both PMA-stimulated human lung epithelial cells (in vitro) and COPD model mice (in vivo). The EtOAc fraction effectively suppresses various inflammatory responses, such as mucus secretion, ROS production, bronchial recruitment of inflammatory cells, and release of proinflammatory cytokines. Additionally, we isolated three compounds with anti-inflammatory efficacy from the EtOAc fraction, out of which daphnodorin C was the most effective. Finally, we demonstrated that daphnodorin C negatively regulates inflammatory gene expression by suppressing NF-κB and specific MAPK signaling pathways (JNK and p38) in vitro and in vivo. CONCLUSIONS: These results suggest that daphnodorin C could be a promising therapeutic alternative for managing COPD symptoms.


Assuntos
Daphne , Doença Pulmonar Obstrutiva Crônica , Animais , Benzopiranos , Humanos , Inflamação/tratamento farmacológico , Pulmão , Camundongos , NF-kappa B , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Fumaça
4.
Mol Med Rep ; 25(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34859262

RESUMO

Methyl p­hydroxycinnamate (MH), an esterified derivative of p­Coumaric acid exerts anti­inflammatory effects on lipopolysaccharide (LPS)­stimulated RAW264.7 macrophages. Based on these effects, the present study investigated the protective role of MH in a mouse model of LPS­induced acute respiratory distress syndrome (ARDS). The results demonstrated that administration of LPS (5 mg/kg intranasally) markedly increased the neutrophil/macrophage numbers and levels of inflammatory molecules (TNF­α, IL­6, IL­1ß and reactive oxygen species) in the bronchoalveolar lavage fluid (BALF) of mice. On histological examination, the presence of inflammatory cells was observed in the lungs of mice administered LPS. LPS also notably upregulated the secretion of monocyte chemoattractant protein­1 and protein content in BALF as well as expression of inducible nitric oxide synthase in the lungs of mice; it also caused activation of p38 mitogen­activated protein kinase (MAPK) and NF­κB signaling. However, MH treatment significantly suppressed LPS­induced upregulation of inflammatory cell recruitment, inflammatory molecule levels and p38MAPK/NF­κB activation, and also led to upregulation of heme oxygenase­1 (HO­1) expression in the lungs of mice. In addition, the ability of MH to induce HO­1 expression was confirmed in RAW264.7 macrophages. Taken together, the findings of the present study indicated that MH may exert protective effects against airway inflammation in ARDS mice by inhibiting inflammatory cell recruitment and the production of inflammatory molecules.


Assuntos
Anti-Inflamatórios/farmacologia , Cinamatos/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/prevenção & controle , Lipopolissacarídeos/toxicidade , Síndrome do Desconforto Respiratório/tratamento farmacológico , Animais , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia , Transdução de Sinais
5.
Biomedicines ; 9(10)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34680566

RESUMO

Microglia play an important role in the maintenance and neuroprotection of the central nervous system (CNS) by removing pathogens, damaged neurons, and plaques. Recent observations emphasize that the promotion and development of neurodegenerative diseases (NDs) are closely related to microglial activation. In this review, we summarize the contribution of microglial activation and its associated mechanisms in NDs, such as epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), based on recent observations. This review also briefly introduces experimental animal models of epilepsy, AD, PD, and HD. Thus, this review provides a better understanding of microglial functions in the development of NDs, suggesting that microglial targeting could be an effective therapeutic strategy for these diseases.

6.
J Microbiol Biotechnol ; 31(11): 1501-1507, 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34489373

RESUMO

Lagerstroemia ovalifolia Teijsm. & Binn. (LO) (crape myrtle) has reportedly been used as traditional herbal medicine (THM) in Java, Indonesia. Our previous study revealed that the LO leaf extract (LOLE) exerted anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Based on this finding, the current study aimed to evaluate the protective effects of LOLE in a mouse model of LPS-induced acute lung injury (ALI). The results showed that treatment with LPS enhanced the inflammatory cell influx into the lungs and increased the number of macrophages and the secretion of the inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of mice. However, these effects were notably abrogated with LOLE pretreatment. Furthermore, the increase of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1) expression in the lung tissues of mice with ALI was also reversed by LOLE. In addition, LOLE significantly suppressed the LPS-induced activation of the MAPK/NF-κB signaling pathway and led to heme oxygenase-1 (HO-1) induction in the lungs. Additionally, in vitro experiments showed that LOLE enhanced the expression of HO-1 in RAW264.7 macrophages. The aforementioned findings collectively indicate that LOLE exerts an ameliorative effect on inflammatory response in the airway of ALI mice.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lagerstroemia/química , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Anti-Inflamatórios/farmacologia , Quimiocina CCL2 , Ciclo-Oxigenase 2 , Citocinas/metabolismo , Heme Oxigenase-1 , Indonésia , Macrófagos/efeitos dos fármacos , Masculino , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II , Folhas de Planta/química , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
7.
Mol Med Rep ; 24(1)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33982762

RESUMO

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/interferon­Î³ (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/metabolismo
8.
Cells ; 10(4)2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33919784

RESUMO

Macrophages play an important role in the innate and adaptive immune responses of organ systems, including the lungs, to particles and pathogens. Cumulative results show that macrophages contribute to the development and progression of acute or chronic inflammatory responses through the secretion of inflammatory cytokines/chemokines and the activation of transcription factors in the pathogenesis of inflammatory lung diseases, such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), ARDS related to COVID-19 (coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), allergic asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). This review summarizes the functions of macrophages and their associated underlying mechanisms in the development of ALI, ARDS, COVID-19-related ARDS, allergic asthma, COPD, and IPF and briefly introduces the acute and chronic experimental animal models. Thus, this review suggests an effective therapeutic approach that focuses on the regulation of macrophage function in the context of inflammatory lung diseases.


Assuntos
Lesão Pulmonar Aguda/patologia , COVID-19/patologia , Macrófagos/patologia , Pneumonia/patologia , Doença Pulmonar Obstrutiva Crônica/patologia , Síndrome do Desconforto Respiratório/patologia , Lesão Pulmonar Aguda/imunologia , Animais , Asma/imunologia , Asma/patologia , COVID-19/imunologia , Doença Crônica , Humanos , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/patologia , Pulmão/imunologia , Pulmão/patologia , Macrófagos/imunologia , Pneumonia/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Síndrome do Desconforto Respiratório/imunologia , SARS-CoV-2/imunologia
9.
J Ethnopharmacol ; 267: 113523, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33129947

RESUMO

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 Cima
10.
Biomed Pharmacother ; 132: 110950, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254440

RESUMO

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/toxicidade
11.
Int Immunopharmacol ; 88: 107002, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33182035

RESUMO

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.


Assuntos
Asma/induzido quimicamente , Asma/tratamento farmacológico , Cinamatos/farmacologia , Macrófagos/efeitos dos fármacos , Animais , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Quimiocinas/genética , Quimiocinas/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/toxicidade , Células RAW 264.7 , Distribuição Aleatória
12.
J Microbiol Biotechnol ; 30(11): 1614-1625, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-32876073

RESUMO

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/metabolismo
13.
Int Immunopharmacol ; 85: 106656, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32504994

RESUMO

3,4,5-Trihydroxycinnamic acid (THCA), a derivative of hydroxycinnamic acid, has been reported to exert anti-inflammatory and antioxidant activities. However, its anti-inflammatory effects in chronic obstructive pulmonary disease (COPD) have not yet been elucidated. Therefore, we explored the protective effects of THCA on pulmonary inflammation in an experimental COPD model elicited by cigarette smoke (CS) and lipopolysaccharide (LPS). Oral administration of THCA significantly inhibited the activity of elastase, the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), myeloperoxidase (MPO) and the numbers of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) of experimental COPD mice. THCA also exerted inhibitory effects on the recruitment of inflammatory cells, the levels of PAS positive cells and cAMP-response-element-binding protein (CREB) activation, and the expression of phosphodiesterase 4 (PDE4) in the lungs of experimental COPD mice. In addition, THCA exerted a regulatory effect on the activation of p38, ERK and nuclear factor-κB (NF-κB) in the lungs of experimental COPD mice. THCA also significantly upregulated the expression of NAD(P)H dehydrogenase (quinone 1) 1 (NQO1) and the activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) in the lungs of mice. Furthermore, THC restored the reduction of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in the lungs of experimental COPD mice. In phorbol myristate acetate (PMA)-stimulated A549 or H292 airway epithelial cells, pretreatment of THCA dose-dependently inhibited the generation of IL-6. THCA also led to increased NQO1 expression in H292 cells. Collectively, these protective effects of antioxidant THCA were notably excellent and are thought to be associated with the downregulation of MAPK (partial)/NF-κB signaling and upregulation of NQO1 and SIRT1 expression.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Cinamatos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Linhagem Celular , Cinamatos/farmacologia , Citocinas/imunologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Camundongos Endogâmicos C57BL , Modelos Animais , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Fumaça/efeitos adversos , Nicotiana
14.
Int J Mol Med ; 44(6): 2171-2180, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638171

RESUMO

Pistacia weinmannifolia (Anacardiaceae) has been used in herbal medicine for the treatment of influenza, dysentery and enteritis in China. It was recently observed that P. weinmannifolia root extract (PWRE) exerts anti­inflammatory effects both in in vitro and in vivo models. Based on the results from previous studies, the present study investigated the protective effect of PWRE on airway inflammation and mucus hypersecretion. Treatment with PWRE significantly decreased the number of eosinophils and the levels of Th2 cytokines, such as interleukin (IL)­4, IL­5 and IL­13, in the bronchoalveolar lavage fluid (BALF) of OVA­exposed mice. PWRE decreased the high serum levels of total and OVA­specific immunoglobulin E. PWRE also effectively inhibited the influx of inflammatory cells into the lung, as well as airway mucus hypersecretion. In addition, the increased level of monocyte chemoattractant protein­1 was significantly decreased with the PWRE treatment in the BALF of OVA­exposed mice and in lipopolysaccharide­stimulated RAW264.7 macrophages. These protective effects of PWRE on OVA­induced pulmonary inflammation were accompanied by the downregulation of mitogen associated protein kinases and nuclear factor­κB activation. Thus, the results from the present study indicate that PWRE could be valuable adjuvant for the treatment of asthma.


Assuntos
Asma/tratamento farmacológico , Pistacia/química , Extratos Vegetais/farmacologia , Pneumonia/tratamento farmacológico , Animais , Antiasmáticos/farmacologia , Asma/induzido quimicamente , Asma/patologia , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , NF-kappa B/genética , Ovalbumina/toxicidade , Extratos Vegetais/química , Raízes de Plantas/química , Pneumonia/induzido quimicamente , Pneumonia/patologia , Células RAW 264.7
15.
Int Immunopharmacol ; 74: 105706, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31254955

RESUMO

Linalool is a natural product present in fruits and aromatic plants with biological activities. Researchers have reported that the inhalation of linalool exerts anti-inflammatory activities. In this study, we examined the therapeutic effects of linalool on airway inflammation and mucus overproduction in mice with allergic asthma. Oral administration of linalool significantly inhibited the levels of eosinophil numbers, Th2 cytokines and immunoglobulin E (IgE) caused by ovalbumin (OVA) exposure. Linalool exerted preventive effects against the influx of inflammatory cells and mucus hypersecretion in the lung tissues. Linalool also dose-dependently decreased the levels of inducible nitric oxide synthase (iNOS) expression and protein kinase B (AKT) activation in the lung tissues. Linalool effectively downregulated the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) caused by OVA exposure. Furthermore, linalool exerted inhibitory effect on OVA-induced airway hyperresponsiveness (AHR). In the in vitro study, the increased secretion of MCP-1 was attenuated with linalool treatment in lipopolysaccharide (LPS)-stimulated H292 airway epithelial cells. In conclusion, linalool effectively exerts a protective role in OVA-induced airway inflammation and mucus hypersecretion, and its protective effects are closely related to the downregulation of inflammatory mediators and MAPKs/NF-κB signaling.


Assuntos
Monoterpenos Acíclicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Hipersensibilidade/tratamento farmacológico , Pulmão/metabolismo , Hipersensibilidade Respiratória/tratamento farmacológico , Células Th2/imunologia , Administração Oral , Alérgenos/imunologia , Animais , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imunoglobulina E/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ovalbumina/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia
16.
Int J Mol Med ; 43(4): 1830-1838, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30816433

RESUMO

Physalis peruviana L. (PP) is well known for its various properties, including its antioxidant property. In our previous study, the protective effects of PP against cigarette smoke­induced airway inflammation were confirmed. The purpose of the present study was to evaluate the anti­inflammatory effect of PP against ovalbumin (OVA)­induced airway inflammation. Treatment with PP inhibited the numbers of eosinophils and the levels of inflammatory cytokines, including interleukin (IL)­4, IL­5 and IL­13, in the bronchoalveolar lavage fluid (BALF) of animal models with OVA­induced allergic asthma. PP also significantly decreased the production of total immunoglobulin E in the serum. Lung sections stained with hematoxylin and eosin revealed that the influx of inflammatory cells was decreased in the lungs of mice treated with PP compared with cells in the OVA group. The increased expression levels of monocyte chemoattractant protein­1 (MCP­1) and T cell marker KEN­5 were also reduced following PP treatment in the lung tissues compared with those in the OVA group. The PAS staining results showed that PP attenuated the overproduction of mucus in the lung. Additionally, western blot analysis revealed that PP significantly downregulated the activation of nuclear factor­κB/p38 mitogen­activated protein kinase/c­Jun N­terminal kinase, and upregulated the expression of heme oxgenase­1 in the lungs. In an in vitro experiment, PP effectively reduced the levels of LPS­stimulated MCP­1 in a concentration­dependent manner. Taken together, these results indicate that PP has considerable potential in the treatment of allergic asthma.


Assuntos
Inflamação/tratamento farmacológico , Pulmão/patologia , NF-kappa B/metabolismo , Physalis/química , Extratos Vegetais/uso terapêutico , Animais , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Quimiocina CCL2/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Eosinófilos/efeitos dos fármacos , Eosinófilos/patologia , Feminino , Heme Oxigenase (Desciclizante)/metabolismo , Imunoglobulina E/sangue , Inflamação/sangue , Inflamação/patologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Pulmão/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Muco/metabolismo , Ovalbumina , Extratos Vegetais/farmacologia , Células RAW 264.7 , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
J Org Chem ; 71(13): 4823-8, 2006 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-16776508

RESUMO

The homoallylic alcohols 3 that can be prepared by the indium-mediated addition of haloallylic sulfones 1 to aldehydes 2 undergo the oxonia-Cope rearrangement with aldehydes 2 to give rise to the allylic sulfones 4 containing a conjugated diene moiety in a highly stereoselective manner. Electron-rich aldehydes preferentially participate in this oxonia-Cope rearrangement with the homoallylic alcohols 3. Excellent correlations of the stereochemistry (anti-3 to trans-allylic sulfone 4 and syn-3 to cis-allylic sulfone 4) have been observed in the oxonia-Cope rearrangement.

18.
Org Lett ; 8(7): 1459-62, 2006 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-16562916

RESUMO

[reaction: see text] The R(1) substituents at C(2) of the haloallylic sulfones 1 play a pivotal role in controlling the diastereoselectivity of the indium-mediated addition reaction to benzaldehyde to produce the homoallylic alcohols 3. The R(1) Me group of 1 prefers the chair form in the In-coordinated six-membered cyclic transition state to give anti-3a, and the R(1) Ph group of 1 favors the twist boat form to give syn-3n, both in a high 13:1 selectivity.

19.
J Org Chem ; 68(20): 7925-7, 2003 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-14510583

RESUMO

An efficient synthetic method for the protected p-hydroquinone compounds 4 containing the C5 trans allylic sulfone moiety has been developed by the direct Friedel-Crafts allylation of the protected dihydroquinone 2 with 4-chloro-2-methyl-1-phenylsulfonyl-2-butene (7a) or 4-hydroxy-2-methyl-1-phenylsulfonyl-2-butene (7b). Expeditious total syntheses of coenzyme Q-10 and vitamin K2(20) have been demonstrated from these valuable key compounds 4a and 4b.

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