RESUMO
Pudilan Xiaoyan Oral Liquid (PDL) originated from "Pudilan" Classic Recipe of traditional Chinese medicine is one kind of anti-inflammatory Chinese patent medicine recorded in Chinese Pharmacopeia. PDL has been used clinically for treating inflammatory diseases of the respiratory tract. However, due to the complex composition of PDL, its potential anti-inflammation and the mechanism remain unknown. To identify the mechanism of the PDL in the treatment of lipopolysaccharide (LPS)-induced lung injury of mice. The mice models of lung injury were established and the changes of biochemical indices in serum and histopathology were detected to explore the effects of PDL. The approach of GC-MS metabolomics was used to find more significant metabolites, and the metabolic pathways were enriched through MetaboAnalyst. Then network analysis was applied to visualize the protein related to the important metabolites, merging into a protein-metabolite network via Cytoscape. The treatment of PDL could attenuate LPS-induced histopathological damage of lung tissues, followed by reducing pro-inflammation mediators including IL-10, TNF-a and NF-ĸB in serum. 11 potential metabolites were identified in lung tissue through metabolomics, which were significantly regulated to recover by PDL treatment. The correlated network was constructed by integrating potential metabolites and pathways. Aspartate and l-cysteine were selected as key metabolites and correlated proteins such as IL4I1 and ASPA were speculated as the potential target to treat LPS-induced lung injury using PDL. These results demonstrated that PDL might prevent the pathological process of lung injury through regulating the disturbed protein-metabolite network.
Assuntos
Anti-Inflamatórios/farmacologia , Lesão Pulmonar/prevenção & controle , Pulmão/efeitos dos fármacos , Pulmão/patologia , Metabolômica/métodos , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Inflamação , Mediadores da Inflamação , Lipopolissacarídeos/farmacologia , Pulmão/imunologia , Pulmão/metabolismo , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
Shufengjiedu capsules (SFJDCs), a traditional Chinese medicine, have been widely used as an antiviral, antibacterial, antitumor, and anti-inflammatory drug. However, the roles of SFJDCs in allergic rhinitis remain unclear. The purpose of this study was to investigate the effects of SFJDCs in olfaction and lung injury in rats with allergic rhinitis. An animal model of allergic rhinitis was created by intraperitoneal injection and intranasal administration of ovalbumin to rats. All rats were divided into seven groups: a model group, a low-dose SFJDC group, a medium-dose SFJDC group, a high-dose SFJDC group, a cetirizine group, and a control group. Hematoxylin and eosin (HE) staining was used to observe pathological changes in rat lung and olfactory epithelium (OE) tissue, and peripheral blood was collected and subjected to an enzyme-linked immunosorbent assay (ELISA) to detect IgE, tumor necrosis factor alpha (TNF-α), and IL-1êµ levels. Western blotting, immunohistochemistry staining, and immunofluorescence staining were performed to detect inflammatory cytokines and levels of the autophagy biomarker beclin1 and the apoptosis biomarker cleaeved-caspased3 in lung and OE tissue. ELISA indicated that SFJDCs significantly decreased IgE, TNF-α, and IL-1êµ levels in peripheral blood, the lungs, and OE tissue. In addition, Western blotting and staining indicated that SFJDCs repair lung injury, protect against neuronal apoptosis in OE, and rescue impaired autophagy in the lungs and OE tissue. In conclusion, results indicated that SFJDCs might protect against neuronal loss in the OE and lung injury by enhancing autophagy and decreasing apoptosis in rats with allergic rhinitis. Therefore, SFJDCs might serve as an alternative treatment for allergic rhinitis.
Assuntos
Autofagia/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Rinite Alérgica/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Inflamação/tratamento farmacológico , Inflamação/imunologia , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Lesão Pulmonar/imunologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Rinite Alérgica/imunologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This paper examined the molecular conformation of Trametes orientalis polysaccharide (TOP-2) and evaluated the ameliorative effects of TOP-2 on PM2.5-induced lung injury in mice. The Congo red test and transmission electron microscopy (TEM) showed that TOP-2 had a triple-helical structure. PM2.5-induced pulmonary edema was ameliorated by TOP-2 intervention. PM2.5 notably increased the number of inflammatory cells and percentages of neutrophils in bronchoalveolar lavage fluid (BALF), and notably reduced the percentages of macrophages in BALF, while TOP-2 abolished these effects. The increased levels of total protein, albumin, C-reactive protein (CRP), myeloperoxidase (MPO), lactate dehydrogenase (LDH), alkaline phosphatase (AKP), acid sphingomyelinase (ASM), TNF-α, IL-1ß and IL-6 in BALF after PM2.5 exposure were inhibited by TOP-2. In addition, TOP-2 could not only remarkably promote the activities of antioxidant enzymes, but also reduce the levels of malondialdehyde (MDA), protein carbonyl group (PCG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Furthermore, TOP-2 up-regulated the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) and inhibited the activation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome in the lung tissue. These results hint that TOP-2 could alleviate PM2.5-induced lung injury in mice via its antioxidant and anti-inflammatory activities, and the underlying mechanisms, at least partly, depended on activation of the Nrf2/HO-1 pathway and inhibition of NLRP3 inflammasome.
Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Lesão Pulmonar/tratamento farmacológico , Material Particulado/efeitos adversos , Polissacarídeos/administração & dosagem , Trametes/química , Animais , Heme Oxigenase-1/genética , Heme Oxigenase-1/imunologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Lesão Pulmonar/etiologia , Lesão Pulmonar/genética , Lesão Pulmonar/imunologia , Masculino , Malondialdeído , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Rimulus cinnamon is the dried twig of Cinnamomum cassia Presl. It is widely used in China for the treatment of inflammatory processes, amenorrhea, and other diseases. We aimed to study the protective effects of ethyl acetate extracts of R. cinnamon (EAE) on systemic inflammation and lung injury in endotoxin-poisoned mice. EAE was administered 5 d prior to lipopolysaccharide (LPS) challenge with 15 mg/kg LPS. The administration of EAE increased the levels of interferon-γ (IFN-γ) and decreased the levels of interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) in the serum. Additionally, EAE relieved the pathological changes in the tissues of the lungs and spleen, and significantly reduced the number of neutrophils in the lung tissues. In addition, treatment with EAE decreased the mRNA expression of the NLR family, pyrin domain-containing protein 3 (NLRP3), caspase-1, and interleukin-1ß (IL-1ß) in the lungs, as well as the expression of NLRP3, caspase-1 (p20), and pro-IL-1ß proteins. These results demonstrated the promising anti-inflammatory effects of EAE in endotoxin-poisoned mice. Furthermore, EAE could alleviate the lung injury of endotoxin-poisoned mice by antagonizing the activation of the NLRP3 inflammasome.
Assuntos
Anti-Inflamatórios/uso terapêutico , Cinnamomum aromaticum/química , Medicamentos de Ervas Chinesas/uso terapêutico , Lipopolissacarídeos/toxicidade , Lesão Pulmonar/prevenção & controle , Pneumonia Bacteriana/prevenção & controle , Acetatos/química , Animais , Anti-Inflamatórios/isolamento & purificação , Citocinas/sangue , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Lesão Pulmonar/sangue , Lesão Pulmonar/imunologia , Masculino , Camundongos Endogâmicos , Pneumonia Bacteriana/sangue , Pneumonia Bacteriana/imunologiaRESUMO
Fish, olive, and coconut oil dietary supplementation have several cardioprotective benefits, but it is not established if they protect against air pollution-induced adverse effects. We hypothesized that these dietary supplements would attenuate ozone-induced systemic and pulmonary effects. Male Wistar Kyoto rats were fed either a normal diet, or a diet supplemented with fish, olive, or coconut oil for 8 weeks. Animals were then exposed to air or ozone (0.8 ppm), 4 h/day for 2 days. Ozone exposure increased phenylephrine-induced aortic vasocontraction, which was completely abolished in rats fed the fish oil diet. Despite this cardioprotective effect, the fish oil diet increased baseline levels of bronchoalveolar lavage fluid (BALF) markers of lung injury and inflammation. Ozone-induced pulmonary injury/inflammation were comparable in rats on normal, coconut oil, and olive oil diets with altered expression of markers in animals fed the fish oil diet. Fish oil, regardless of exposure, led to enlarged, foamy macrophages in the BALF that coincided with decreased pulmonary mRNA expression of cholesterol transporters, cholesterol receptors, and nuclear receptors. Serum microRNA profile was assessed and demonstrated marked depletion of a variety of microRNAs in animals fed the fish oil diet, several of which were of splenic origin. No ozone-specific changes were noted. Collectively, these data indicate that although fish oil offered vascular protection from ozone exposure, it increased pulmonary injury/inflammation and impaired lipid transport mechanisms resulting in foamy macrophage accumulation, demonstrating the need to be cognizant of potential off-target pulmonary effects that might offset the overall benefit of this vasoprotective supplement.
Assuntos
Aorta/efeitos dos fármacos , Gorduras na Dieta/administração & dosagem , Lesão Pulmonar/induzido quimicamente , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Ozônio/toxicidade , Animais , Aorta/fisiopatologia , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Óleo de Coco/administração & dosagem , Óleos de Peixe/administração & dosagem , Células Espumosas/citologia , Inflamação , Lesão Pulmonar/imunologia , Lesão Pulmonar/fisiopatologia , Masculino , Músculo Liso Vascular/fisiopatologia , Azeite de Oliva/administração & dosagem , Ratos Endogâmicos WKYRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Pudilan xiaoyan oral liquid (PDL), collected in Chinese Pharmacopoeia, has been used clinically for treating inflammatory diseases such as upper respiratory tract infection diseases. However, its potential anti-inflammation and the mechanism are still unclear. MATERIALS AND METHODS: lipopolysaccharide (LPS) was used to induce respiratory inflammation of mice by intratracheal administration. UPLC/MS was performed for components analysis of PDL. Enzyme-linked immune sorbent assay (ELISA) was conducted for determining interleukin-6(IL-6), interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) in serum and supernatant of tracheal tissue while Nitric oxide assay kit for nitric oxide (NO) content. Hematoxylin-Eosin (HE) staining was applied to evaluate pathological lesions. Western blotting analysis (WB) and Immunohistochemistry(IHC) were employed for the determination of Toll-like receptors 4(TLR4), TNF-α, IL-6, inducible nitric oxide synthase(iNOS) and nuclear factor-kappa B p65 (NF-κB p65) protein expressions. RESULTS: Seven major compounds of PDL were analyzed simultaneously. The treatment of PDL could attenuate LPS-induced histopathological damage of tracheal tissues, followed by reducing pro-inflammation mediators including TNF-α and IL-6 in serum and supernatant of tracheal tissue. LPS-induced nitroxidative stress including NO content and iNOS expression was inhibited significantly by PDL. Furthermore, PDL also down-regulated NF-kB p65 phosphorylation and TLR4 expressions. CONCLUSION: The results indicated that the PDL had a protective effect on LPS-induced respiratory inflammation injury in mice. Our findings for the first time provide experimental evidence for the application of PDL on respiratory inflammation injury in clinical practice.
Assuntos
Anti-Inflamatórios/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Lipopolissacarídeos , Lesão Pulmonar/prevenção & controle , Pulmão/efeitos dos fármacos , Estresse Nitrosativo/efeitos dos fármacos , Receptor 4 Toll-Like/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Administração Oral , Animais , Modelos Animais de Doenças , Mediadores da Inflamação/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/imunologia , Lesão Pulmonar/metabolismo , Masculino , Camundongos Endogâmicos ICR , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelA/imunologia , Fator de Necrose Tumoral alfa/sangueRESUMO
The incidence and mortality rates of bronchopulmonary dysplasia (BPD) remain very high. Therefore, novel therapies are imminently needed to improve the outcome of this disease. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) show promising therapeutic effects on oxygen-induced model of BPD. In our experiment, UC-MSCs were intratracheally delivered into the newborn rats exposed to hyperoxia, a well-established BPD model. This study demonstrated that UC-MSCs reduce elastin expression stimulated by 90% O2 in human lung fibroblasts-a (HLF-a), and inhibit HLF-a transdifferentiation into myofibroblasts. In addition, the therapeutic effects of UC-MSCs in neonatal rats with BPD, UC-MSCs could inhibit lung elastase activity and reduce aberrant elastin expression and deposition in the lung of BPD rats. Overall, this study suggested that UC-MSCs could ameliorate aberrant elastin expression in the lung of hyperoxia-induced BPD model which may be associated with suppressing increased TGFß1 activation.
Assuntos
Displasia Broncopulmonar/imunologia , Displasia Broncopulmonar/patologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Elastina/metabolismo , Pulmão/imunologia , Pulmão/patologia , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Animais Recém-Nascidos , Células Cultivadas , Humanos , Oxigenoterapia Hiperbárica , Hiperóxia/metabolismo , Hiperóxia/patologia , Hiperóxia/prevenção & controle , Lesão Pulmonar/imunologia , Lesão Pulmonar/patologia , Lesão Pulmonar/prevenção & controle , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
Supplemental oxygen (O2) increases the risk of lung injury in preterm infants, owing to an immature antioxidant system. Our objective was to determine whether impairing antioxidant defense by decreasing glutathione peroxidase 1 (GPx1) gene expression increases the injurious effects of hyperoxia (Hyp). GPx1+/+ and GPx1-/- C57Bl/6J mice were exposed to 21% O2 (Air) or 40% O2 (Hyp) from birth to postnatal day 7 (P7d); they were euthanized on P7d or maintained in air until adulthood [postnatal day 56 (P56d)] to assess short-term and long-term effects, respectively. We assessed lung architecture, three markers of pulmonary oxidative stress (P7d, P56d), macrophages in lung tissue (P7d), immune cells in bronchoalveolar lavage fluid (BALF; P56d), and GPx1-4 and catalase gene expression in lung tissue (P7d, P56d). On P7d, macrophages were decreased by lack of GPx1 expression and further decreased by hyperoxia. GPx1 expression was increased in GPx1+/+Hyp mice and decreased in both GPx1-/- groups. On P56d, heme oxygenase-1 was increased by hyperoxia when GPx1 was absent. There were significantly more immune cells from Hyp groups than from the GPx1+/+Air group and a greater proportion of lymphocytes in GPx1-/-Hyp mice. GPx1 expression was significantly decreased in GPx1-/- mice; GPx2-4 and catalase expression was increased in GPx1-/-Hyp mice compared with other groups. Tissue fraction was decreased in GPx1-/-Air mice; bronchiolar smooth muscle was decreased in GPx1-/- mice. GPx1 does not clearly exacerbate hyperoxia-induced increases in oxidative stress or lung injury but may alter pulmonary immune function. Increased expression of GPx2-4 and catalase in GPx1-/-Hyp mice suggests gene redundancy within the model.
Assuntos
Progressão da Doença , Regulação Enzimológica da Expressão Gênica , Glutationa Peroxidase/genética , Hiperóxia/enzimologia , Hiperóxia/genética , Lesão Pulmonar/enzimologia , Lesão Pulmonar/genética , Aldeídos/metabolismo , Animais , Animais Recém-Nascidos , Antioxidantes/metabolismo , Feminino , Glutationa Peroxidase/metabolismo , Heme Oxigenase-1/metabolismo , Pulmão/imunologia , Pulmão/patologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/patologia , Masculino , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Tirosina/análogos & derivados , Tirosina/metabolismo , Glutationa Peroxidase GPX1RESUMO
This study aimed to investigate the protective effects of hyperbaric oxygen preconditioning (HBO-PC) on acute pancreatitis AP associated acute lung injury (ALI) and the potential mechanisms. Rats were randomly divided into sham group, AP group, HBO-PC + AP group and HBO-PC + L-NAME group. Rats in HBO-PC + AP group received HBO-PC once daily for 3 days, and AP was introduced 24 h after last HBO-PC. In HBO-PC + L-NAME group, L-NAME (40 mg/kg) was intraperitoneally injected before each HBO-PC. At 24 h after AP, the blood lipase and amylase activities were measured; the lung and pancreas were harvested for pathological examination; the bronchoalveolar lavage fluid was collected for the detection of lactate dehydrogenase (LDH) and proteins; inflammatory factors, superoxide dismutase (SOD) activity and malonaldehyde content were measured in the lung and blood; the Nrf2, SOD-1 and haem oxygenase-1 (HO-1) protein expression was measured in the lung. The lung nitric oxide (NO) and NO synthase activity increased significantly after HBO-PC. HBO-PC was able to reduce blood lipase and amylase activities, improve lung and pancreatic pathology, decrease LDH and proteins in BALF, inhibit the production of inflammatory factors, reduce malonaldehyde content and increase SOD activity in the lung and blood as well as increase protein expression of Nrf2, SOD-1 and HO-1 in the lung. However, L-NAME before HBO-PC significantly attenuated protective effects of HBO-PC. HBO-PC is able to protect the lung against AP induced injury by attenuating inflammation and oxidative stress in the lung via a NO dependent manner.
Assuntos
Oxigenoterapia Hiperbárica/métodos , Inflamação/etiologia , Inflamação/terapia , Lesão Pulmonar/etiologia , Lesão Pulmonar/terapia , Pancreatite/complicações , Pancreatite/terapia , Animais , Inflamação/imunologia , Inflamação/patologia , Pulmão/imunologia , Pulmão/patologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/patologia , Masculino , Óxido Nítrico/análise , Óxido Nítrico/imunologia , Estresse Oxidativo , Pâncreas/imunologia , Pâncreas/patologia , Pancreatite/imunologia , Pancreatite/patologia , Ratos Sprague-DawleyRESUMO
Staphylococcus aureus, like other gram-positive pathogens, has evolved a large repertoire of virulence factors as a powerful weapon to subvert the host immune system, among which alpha-hemolysin (Hla), a secreted pore-forming cytotoxin, plays a preeminent role. We observed a concentration-dependent reduction in Hla production by S. aureus in the presence of sub-inhibitory concentrations of isorhamnetin, a flavonoid from the fruits of Hippophae rhamnoides L., which has little antibacterial activity. We further evaluate the effect of isorhamnetin on the transcription of the Hla-encoding gene hla and RNAIII, an effector molecule in the agr system. Isorhamnetin significantly down-regulated RNAIII expression and subsequently inhibited hla transcription. In a co-culture of S. aureus and lung cells, topical isorhamnetin treatment protected against S. aureus-induced cell injury. Isorhamnetin may represent a leading compound for the development of anti-virulence drugs against S. aureus infections.
Assuntos
Toxinas Bacterianas/genética , Proteínas Hemolisinas/genética , Hippophae/química , Lesão Pulmonar/tratamento farmacológico , Extratos Vegetais/farmacologia , Quercetina/análogos & derivados , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/toxicidade , Regulação para Baixo/efeitos dos fármacos , Proteínas Hemolisinas/metabolismo , Proteínas Hemolisinas/toxicidade , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Lesão Pulmonar/genética , Lesão Pulmonar/imunologia , Quercetina/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/metabolismoRESUMO
Mindfulness-based Stress Reduction (MBSR) is a treatment program for relieving stress and coping with chronic illnesses. In recent three decades, studies have shown that MBSR has a positive effect on physical and psychological dimensions of chronic illnesses. Chemically pulmonary injured veterans have chronic pulmonary and psychological problems due to mustard gas exposure and complications of Iran-Iraq war. These stresses have negative effects on their general health and immune system. To the best of our knowledge, this is the first study conducted on psychoneuroimmunology and MBSR in these patients. Forty male pulmonary injured veterans were randomly divided in two groups with 20 participants (MBSR and wait-list control). Then MBSR group received 8 weekly sessions of intervention. We tested mental health based on general health questionnaire (GHQ)-28 questionnaire, health-related quality of life (based on St. George respiratory questionnaire (SGRQ) ) and immunity in MBSR groups; before and after intervention "mixed factorial analyses of variance" test was used for analyzing data fpr each dependent variable and appropriate t-tests were done in The necessary condition. Results showed that mental health and health- related quality of life, in MBSR group compared to wait-list control improved [F (1,38)=26.46, p<0.001; F (1,38)=49.52, p<0.001 respectively] significantly. Moreover, a significant increase was reported in the lymphocyte proliferation with phytohemagglutinin (PHA) [F (1,38)=16.24, p<0.001], and peripheral blood IL-17 [F (1,38)=56.71, p<0.001] However, lymphocyte (CD4+, CD8+, and NK-cell) percentages were not affected significantly [F (1,38)=2.21, p=0.14] ,[F (1,38)=0.90, p=0.78] and [F (1,38)=1.79, p=0.18], respectively. This study suggests that MBSR may be a new treatment approach for improving immunity and overall health in chemically pulmonary injured veterans.
Assuntos
Lesão Pulmonar/psicologia , Saúde Mental , Atenção Plena/métodos , Qualidade de Vida , Estresse Psicológico/terapia , Veteranos/psicologia , Adulto , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células , Substâncias para a Guerra Química/intoxicação , Doença Crônica , Humanos , Interleucina-17/imunologia , Irã (Geográfico) , Células Matadoras Naturais/imunologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Gás de Mostarda/intoxicação , Estresse Psicológico/imunologia , Estresse Psicológico/psicologia , Inquéritos e QuestionáriosRESUMO
Sepsis, which is caused by severe infection, is an important cause of mortality, but effective clinical treatment against sepsis is extremely limited. As the main component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) plays a major role in inflammatory responses. Studies have shown beneficial pharmacological effects for Folium isatidis. The present study further illuminated the effects of n-butanol extract from Folium isatidis in LPS-induced septic shock and identified the main active chemical components. Our study showed that pretreatment with n-butanol extract from Folium isatidis not only significantly inhibited LPS-induced tumor necrosis factor-α and interleukin-6 production but also markedly and dose dependently enhanced the recruitment of MyD88, the phosphorylation of extracellular signal-regulated kinase, and the degradation of IκB-α. Additionally, the extract exhibited dramatic protective effects against lung injury and death in mice with septic shock. Eight main active compounds were identified, including organic acids, glycoside, indolinones, and flavonoids. These findings provide a perspective on the respiratory protection offered by n-butanol extract from Folium isatidis in LPS-induced sepsis and outline a novel therapeutic strategy for the treatment of sepsis.
Assuntos
1-Butanol/química , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Mediadores da Inflamação/metabolismo , Isatis/química , Lipopolissacarídeos , Macrófagos Peritoneais/efeitos dos fármacos , Choque Séptico/prevenção & controle , Solventes/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Citocinas/imunologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas I-kappa B/metabolismo , Mediadores da Inflamação/imunologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/imunologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/prevenção & controle , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/metabolismo , Inibidor de NF-kappaB alfa , Fosforilação , Fitoterapia , Folhas de Planta , Plantas Medicinais , Proteólise , Choque Séptico/induzido quimicamente , Choque Séptico/imunologia , Choque Séptico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Espectrometria de Massas em Tandem , Fatores de TempoRESUMO
Canarium lyi C.D. Dai & Yakovlev (CL) is a member of the Anacardiaceae family. To the best of our knowledge, no studies on its anti-inflammatory effects have yet been reported. In the present study, we investigated the protective effects of CL on inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and LPS-induced acute lung injury (ALI) mice. CL attenuated the production of LPS-stimulated inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and interleukin-6 (IL-6). Furthermore, CL suppressed phosphorylation of the inhibitor κB-α (IκB-α), p38, c-Jun terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), as well as the translocation of the nuclear factor-κB (NF-κB) p65 subunit into the nucleus. For the in vivo efficacy, the effect of CL on a mouse model of LPS-induced acute lung injury was assessed. CL treatment of the mice significantly inhibited the inflammatory cell recruitment and pro-inflammatory cytokine production in bronchoalveolar lavage fluids (BALF). CL-treated mice also showed a marked inhibition of cyclooxygenase-2 (COX-2) and phosphorylation of IκB and p65. In addition, CL attenuated lung histopathological changes in LPS-induced ALI mice. In conclusion, our results suggest that CL is a potential therapeutic candidate for the treatment of inflammatory diseases, including pneumonia.
Assuntos
Anacardiaceae/química , Anti-Inflamatórios/farmacologia , Lesão Pulmonar/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Extratos Vegetais/farmacologia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/biossíntese , Citocinas/genética , Dinoprostona/biossíntese , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/efeitos adversos , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/imunologia , Lesão Pulmonar/patologia , Macrófagos/imunologia , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno , NF-kappa B/metabolismo , Nitritos/metabolismoRESUMO
Asiaticoside (AS), a major triterpenoid saponin component isolated from Centella asiatica, has been described to exhibit antioxidant and anti-inflammatory activities. The present study aimed to determine the protective effects and the underlying mechanisms of AS on septic lung injury induced by cecal ligation and puncture (CLP). Mice were pretreated with the AS (45 mg/kg) or AS as well as GW9662 at 1h before CLP, the survival, lung injury, inflammatory mediators and signaling molecules, and Peroxisome proliferator-activated receptor-γ (PPAR-γ) were determined 24 h after CLP. The results showed that AS significantly decreased CLP-induced the mortality, lung pathological damage, the infiltration of mononuclear, polymorphonuclear (PMN) leucocytes and total proteins. Moreover, AS inhibited CLP-induced the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB), the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein in lung tissues, and the production of serum tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Interestingly, the expression of PPAR-γ protein in lung tissue was up-regulated by AS. Furthermore, GW9662 (the inhibitor of PPAR-γ) significantly reversed these beneficial effects of AS in septic mice. These findings suggest that AS could effectively protect from septic lung injury induced by CLP and the underlying mechanisms might be related to up-regulation of PPAR-γ expression to some extent, which inhibits MAPKs and NF-κB pathway.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Pulmão/efeitos dos fármacos , Pneumonia Bacteriana/tratamento farmacológico , Triterpenos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/isolamento & purificação , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Western Blotting , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Centella/química , Ciclo-Oxigenase 2/biossíntese , Citocinas/sangue , Modelos Animais de Doenças , Contagem de Leucócitos , Pulmão/enzimologia , Pulmão/imunologia , Pulmão/patologia , Lesão Pulmonar/enzimologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/biossíntese , PPAR gama/biossíntese , Pneumonia Bacteriana/enzimologia , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/patologia , Triterpenos/administração & dosagem , Triterpenos/isolamento & purificaçãoRESUMO
AIM: To investigate the effect of Gardenia jasminoides (GJ) on cerulein-induced acute pancreatitis (AP) in mice. METHODS: C57BL/6 mice weighing 18-20 g were divided into three groups. (1) Normal saline-treated group, (2) treatment with GJ at a dose of 0.1 g/kg, (3) treatment with GJ at a dose of 1 g/kg. GJ was administered orally (n = 6 per group) for 1 wk. Three hours later, the mice were given an intraperitoneal injection of cerulein (50 microg/kg), a stable cholecystokinin (CCK) analogue, every hour for a total of 6 h as described previously. The mice were sacrificed at 6 h after completion of cerulein injections. Blood samples were obtained to determine serum amylase, lipase and cytokine levels. The pancreas was rapidly removed for morphologic examination and scoring. A portion of pancreas was stored at -70 degree and prepared for the measurement of tissue myeloperoxidase (MPO) activity, an indicator of neutrophil sequestration, and for reverse-transcriptase PCR (RT-PCR) and real-time PCR measurements. RESULTS: Treatment with GJ decreased significantly the severity of pancreatitis and pancreatitis-associated lung injury. Treatment with GJ attenuated the severity of AP compared with saline-treated mice, as shown by reduction in pancreatic edema, neutrophil infiltration, serum amylase and lipase levels, serum cytokine levels, and mRNA expression of multiple inflammatory mediators. CONCLUSION: These results suggest that GJ attenuated the severity of AP as well as pancreatitis-associated lung injury.