RESUMO
Ethnopharmacological Relevance. Atopic dermatitis is a chronic inflammatory skin disease. Lagerstroemia ovalifolia Teijsm. & Binn. (LO) has traditionally been used as an herbal medicine for anti-inflammatory diseases. The effect of LO on atopic dermatitis has not been verified scientifically. We investigated the effects of CHCl3 fraction number 5 of LO (LOC) on atopic dermatitis through cell-based experiments. HaCaT cells were treated with tumor necrosis factor-alpha (TNFα)/interferon-gamma (IFNγ) to induce an inflammatory reaction. Proinflammatory cytokines, interleukin- (IL-) 6, IL-8, and IL-1ß and chemokines such as thymus and activation-regulated chemokine (TARC/CCL17), monocyte chemoattractant protein 1 (MCP1/CCL2), and macrophage-derived chemokine (MDC/CCL22) were measured by RT-PCR and ELISA. In addition, the degree of phosphorylation and activation of JAK/STAT1, PI3K/AKT, and nuclear factor-kappa B (NF-κB) were measured by western blot and luciferase assays. The production of inflammatory cytokines and chemokines and activation of the JAK/STAT1, PI3K/AKT, and NF-κB pathways were induced by TNFα/IFNγ in HaCaT cells. Under these conditions, LOC treatment inhibited the production of targeted cytokines and chemokines and decreased the phosphorylation and activation of JAK/STAT1, PI3K/AKT, and NF-κB. These results suggest that LOC reduces the production of proinflammatory cytokines and chemokines by suppressing the JAK/STAT1, PI3K/AKT, and NF-κB pathways. Therefore, LOC may have potential as a drug for atopic dermatitis.
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/metabolismoRESUMO
Physalis peruviana L. (PP) is a medicinal herb that has been confirmed to have several biological activities, including anticancer, antioxidant and anti-inflammatory properties. The aim of the present study was to evaluate the protective effect of PP on cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced pulmonary inflammation. Treatment with PP significantly reduced the influx of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and lung of mice with CS- and LPS-induced pulmonary inflammation. PP also decreased the levels of reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF. PP effectively attenuated the expression of monocyte chemoattractant protein-1 (MCP-1) and the activation of extracellular signal-regulated kinase (ERK) in the lung. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) activation and heme oxygenase-1 (HO-1) expression were increased by PP treatment. In an in vitro experiment, PP reduced the mRNA expression of TNF-α and MCP-1, and the activation of ERK in CS extract-stimulated A549 epithelial cells. Furthermore, PP increased the activation of Nrf2 and the expression of HO-1 in A549 cells. These findings suggest that PP has a therapeutic potential for the treatment of pulmonary inflammatory diseases, such as chronic obstructive pulmonary disease.
Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Heme Oxigenase-1/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Lipopolissacarídeos/efeitos adversos , Physalis/química , Extratos Vegetais/farmacologia , Fumar/efeitos adversos , Animais , Biomarcadores , Líquido da Lavagem Broncoalveolar/citologia , Linhagem Celular Tumoral , Quimiocina CCL2/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Heme Oxigenase-1/genética , Humanos , Inflamação/patologia , Mediadores da Inflamação , Leucócitos/metabolismo , Leucócitos/patologia , Masculino , Camundongos , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Neutrófilos/patologia , Extratos Vegetais/química , Espécies Reativas de Oxigênio , Mucosa Respiratória/metabolismo , Doenças Respiratórias/etiologia , Doenças Respiratórias/metabolismo , Doenças Respiratórias/patologiaRESUMO
Lagerstroemia ovalifolia Teijsm. & Binn. has traditionally been used as an herbal medicine and possesses anti-inflammatory properties. However, the mechanisms underlying its anti-inflammatory effects remain poorly understood. For this purpose, we aimed to investigate the effects of methanolic extract of L. ovalifolia (LOME) on nitric oxide (NO) and prostaglandin E2 (PGE2) production, as well as the underlying molecular mechanisms responsible for these effects, in lipopolysaccharide (LPS)stimulated RAW264.7 macrophages. We examined the effects of LOME on the production of NO and PGE2 in LPS-stimulated RAW264.7 cells. To explore the anti-inflammatory mechanisms of LOME, we measured the mRNA or protein expression of the proinflammatory mediators induced by LOME in the LPS-stimulated RAW264.7 cells. LOME significantly inhibited the production of NO, PGE2, interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α) in LPS-stimulated RAW264.7 cells. Moreover, LOME suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and inhibited the phosphorylation of the mitogen-activated protein kinases (MAPKs), with a reduction in the nuclear translocation of nuclear factor (NF)-κB in LPS-stimulated RAW264.7 cells. Taken together, these findings suggest that LOME may exert anti-inflammatory effects in vitro in LPS-stimulated RAW264.7 macrophages and thus, may have potential for use as an adjuvant treatment of inflammatory diseases.