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Atopic dermatitis (AD) is an allergic, inflammatory skin disease caused by immune dysregulation. In this study, we investigated anti-atopic and anti-inflammatory activities of Sanguisorba hakusanensis ethanol extract (SHE) both in vivo using NC/Nga mice and in vitro using human HaCaT keratinocytes. Oral administration of SHE suppressed several atopic symptoms associated with house dust mites (induced with Dermatophagoides farinae extract) in NC/Nga mice and decreased serum levels of inflammatory mediators such as immunoglobulin E, histamine, and inflammatory chemokines. Additionally, SHE treatment reduced the infiltration of immune cells such as mast cells and macrophages in AD skin lesions. In vitro, interferon-γ- and tumor necrosis factor-α-stimulated HaCaT cells exhibited increased expression of T helper 1 and 2 chemokines; their expression was inhibited by SHE treatment. The anti-inflammatory effects of SHE treatment involved blocking of the mitogen-activated protein kinase and signal transducer and activator of transcription 1 signaling pathways. In conclusion, SHE exerts potent anti-atopic and anti-inflammatory effects and should be considered for the clinical treatment of AD.
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Dermatite Atópica , Sanguisorba , Humanos , Animais , Camundongos , Queratinócitos , Células HaCaT , EtanolRESUMO
Atopic dermatitis (AD) is chronic allergic contact dermatitis with immune dysregulation. Veronica persica has pharmacological activity that prevents asthmatic inflammation by ameliorating inflammatory cell activation. However, the potential effects of the ethanol extract of V. persica (EEVP) on AD remain elusive. This study evaluated the activity and underlying molecular pathway of EEVP in two AD models: dinitrochlorobenzene (DNCB)-induced mice and interferon (IFN)-γ/tumor necrosis factor (TNF)-α-stimulated human HaCaT keratinocytes. EEVP attenuated the DNCB-induced increase in serum immunoglobulin E and histamine levels, mast cell counts in toluidine-blue-stained dorsal skin, inflammatory cytokine (IFN-γ, interleukin [IL]-4, IL-5, and IL-13) levels in cultured splenocytes, and the mRNA expression of IL6, IL13, IL31 receptor, CCR-3, and TNFα in dorsal tissue. Additionally, EEVP inhibited the IFN-γ/TNF-α-induced mRNA expression of IL6, IL13, and CXCL10 in HaCaT cells. Furthermore, EEVP restored the IFN-γ/TNF-α-induced downregulation of heme oxygenase (HO)-1 in HaCaT cells by inducing nuclear factor erythroid 2-related factor 2 (Nrf2) expression. A molecular docking analysis demonstrated that EEVP components have a strong affinity to the Kelch-like ECH-associated protein 1 Kelch domain. In summary, EEVP inhibits inflammatory AD by attenuating immune cell activation and inducing the Nrf2/HO-1 signaling pathway in skin keratinocytes.
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Veronica persica is a flowering plant belonging to the family Scrophulariaceae. Here, we aimed to evaluate the pharmacological activity of the ethanol extract of Veronica persica (EEVP) in an airway inflammation model. We examined airway responsiveness to aerosolized methacholine, serum immunoglobulin (Ig)E levels, and total cell numbers in the lung and bronchoalveolar lavage fluid (BALF). Histological analysis of the lung tissue was performed using hematoxylin-eosin, Masson trichrome, or periodic acid-Schiff staining. Fluorescence-activated cell sorting analysis in the lung and BALF was applied to clarify the changes in immune cell types. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction were applied to investigate cytokine levels and gene expression related to airway inflammation. STAT-3/6 phosphorylation was examined in primary bronchial/tracheal epithelial cells using western blot analysis. EEVP significantly suppressed total IgE levels and methacholine-induced increase of Penh value in the HDM-challenged mouse model. EEVP also attenuated the severity of airway remodeling in lung tissues and decreased eosinophil and neutrophil infiltration in the lungs and BALF. EEVP significantly reduced the production of cytokines in BAL and splenocyte culture medium, and the expression of mRNAs related to airway inflammation in the lung tissue. EEVP suppressed IL-4/13-induced STAT-3/6 phosphorylation in the epithelial cells. We showed for the first time that EEVP effectively inhibits eosinophilic airway inflammation by suppressing the expression of inflammatory factors for T cell activation and polarization, and inhibits MCP-1 production of bronchial/tracheal epithelial cells by suppressing STAT-3/6 activation. EEVP may be a potential pharmacological agent to prevent inflammatory airway diseases.
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Asma , Veronica , Animais , Asma/metabolismo , Citocinas/metabolismo , Etanol/farmacologia , Imunoglobulina E , Inflamação/metabolismo , Pulmão , Cloreto de Metacolina/metabolismo , Camundongos , PyroglyphidaeRESUMO
Anethum graveolens L. (dill seeds) are important medicinal and functional foods in Europe and central and south Asia, often used as a seasoning in daily diets. Anethum graveolens L. seeds (AGS) are used to treat indigestion and have shown physiological activities such as those against hypoglycemia and gastroesophageal disease. This study explored the protective effects of AGS extract on mucosal damages and inflammation in reflux esophagitis rats. AGS inhibited cellular inflammation including NO production and the expression of inflammatory proteins (iNOS and COX2 etc.), cytokines (IL-1ß and TNF-α) and nuclear transfer factor related to NF-κB signaling caused by LPS stimulation in vitro. Furthermore, reflux esophagitis-induced rats were used to observe the anti-inflammatory effect of AGS. Tissue staining and inflammation-related protein expression of rats with acute reflux esophagitis indicated that AGS improved this inflammatory response, such as COX-2 and TNF-α in mucosa. In conclusion, AGS have good physiological activity and the possibility of being used as a medicinal food and a functional resource for the prevention and therapy of gastroesophageal diseases.
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This experiment was to explore the possible defensive properties and potential molecular mechanisms of Camellia japonica (CJ) against APAP-stimulated acute liver failure (ALF) in mice. In this study, we investigated the effects of CJ on APAP-induced hepatotoxicity. Mice were orally treated with CJ before or after challenge with APAP. Both pretreatment and post-treatment with CJ attenuated APAP-induced hepatotoxicity, as confirmed by significantly reduced serum toxicity biomarkers and improved hepatic pathological damage. Pretreatment with CJ drastically decreased the rise of hepatic inflammatory cytokines levels and weakened neutrophil infiltration. Furthermore, pretreatment with CJ dramatically decreased the levels of hepatic oxidative stress markers such as hepatic malondialdehyde (MDA) and 4-Hydroxynonenal (4-HNE) expression and rescued the reduced hepatic level of GSH caused by APAP overdose. Additionally, CJ pretreatment markedly attenuated cyclooxygenase-2 (COX-2) activation, transcription factor nuclear factor-kappa B (NF-κB) phosphorylation, c-Jun-N-terminal kinase (JNK) phosphorylation, and activated AMP-activated protein kinase (AMPK) signaling pathway in the liver. The present study thus reveals that CJ attenuated APAP-induced ALF by inhibiting COX-2 activation, NF-κB, and JNK phosphorylation and activating the AMPK signaling pathway.
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Camellia , Doença Hepática Induzida por Substâncias e Drogas , Falência Hepática Aguda , Acetaminofen/toxicidade , Animais , Falência Hepática Aguda/induzido quimicamente , Camundongos , Estresse OxidativoRESUMO
BACKGROUND: Excessive and continuous inflammation may be the main cause of various immune system diseases. Reflux esophagitis (RE) is a common gastroesophageal reflux disease (GERD). Camellia japonica has high medicinal value and has long been used as a traditional herbal hemostatic medicine in China and Korea. The purpose of this study is to explore the antioxidant and anti-inflammatory activities of CJE and its protective effect on RE. MATERIALS AND METHODS: Buds from C. japonica plants were collected in the mountain area of Jeju, South Korea. Dried C. japonica buds were extracted with 75% ethanol. DPPH and ABTS radical scavenging assay were evaluated according to previous method. The ROS production and anti-inflammatory effects of C. japonica buds ethanol extract (CJE) were evaluated on LPS-induced RAW 264.7 cell inflammation. The protective effects of CJE on RE were conducted in a RE rat model. RESULTS: CJE eliminated over 50% of DPPH and ABTS radical at concentration of 100 and 200 µg/mL, respectively. CJE alleviated changes in cell morphology, reduced production of ROS, NO and IL-1ß. Also, down-regulated expression levels of iNOS, TNF-α, phosphorylated NF-κB, IκBα, and JNK/p38/MAPK. CJE reduced esophageal tissue damage ratio (40.3%) and attenuation of histological changes. In addition, CJE down-regulated the expression levels of TNF-α, IL-1ß, COX-2 and phosphorylation levels of NF-κB and IκBα in esophageal tissue. CONCLUSIONS: CJE possesses good anti-oxidation and anti-inflammatory activity, and can improve RE in rats caused by gastric acid reflux. Therefore, CJE is a natural material with good anti-oxidant and anti-inflammatory activity and has the possibility of being a candidate phytomedicine source for the treatment of RE.
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ETHNOPHARMACOLOGICAL RELEVANCE: Geranii Herba, the traditional medicinal plants Korean and northeast China, has been used in the healing of a variety of gastrointestinal inflammation disorders. Geranium koreanum is a congeneric origin plant of Geranii Herba that can be used as medicinal plants with Geranium thunbergii, Geranium sibiricum, Geranium carolinianum, Geranium nepalense, and Geranium japonicam. However, research on the biological activity of Geranium koreanum is currently insufficient. AIM OF THE STUDY: Gastritis is typically characterized by inflammation and irritation, and it is commonly caused by factors such as stress, alcohol consumption, smoking, and the use of anti-inflammatory drugs. In particular, excessive ethanol ingestion is an important cause of gastric disease mediated by mucosal damage by inflammatory cells infiltration. In this study, we investigated whether Geranium koreanum, the well-known traditional medicinal plant, could have a protective effect on gastric mucosal damage in an HCl/EtOH-induced gastritis model by analyzing the inflammation response in gastric tissue. MATERIAL AND METHODS: The cytotoxicity and anti-inflammatory effects of Geranium koreanum were analyzed by determining cell viability and nitric oxide (NO) production, as well as the levels of nuclear factor (NF)-κB proteins in lipopolysaccharide (LPS)-induced cells. Additionally, we measured the damage ratio, conducted histopathological assay by H&E and PAS staining, and determined the levels of pro-inflammation mediator proteins in gastric tissue after induction of gastritis by HCl/EtOH administration in order to analyze the gastro-protective effects of Gerranium koreanum. RESULTS: The ulcer ratio and inflammatory cell infiltration in gastric mucosa were reduced by treatment with Geranium koreanum. Additionally, the expression of inflammatory mediators in gastric tissue was effectively decreased by extracts administrated at 200â¯mg/kg, as compared to the gastritis control. CONCLUSIONS: We demonstrated that Geranium koreanum could have ameliorating effects against HCl/EtOH-induced gastritis through the anti-inflammatory response, which indicates the potential use of this plant as a natural preventive medicine for gastritis treatment.
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Anti-Inflamatórios/farmacologia , Gastrite/prevenção & controle , Geranium/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Células RAW 264.7RESUMO
Gastroesophageal reflux disease (GERD) is a disease that stomach contents continually refluxing into esophagus causes symptoms and/or complications. The study was working to find natural plant extracts with good effects and small side effects to treat reflux esophagitis (RE). The anti-inflammatory effects of hexane extract of Magnolia sieboldii (MsHE) were conducted on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The ameliorative effects of MsHE on esophageal damage in rats induced by gastric acid reflux was explored in vivo. The results showed that MsHE decreased the production of nitric oxide (NO) and expression levels of iNOS, COX-2 and TNF-α on LPS-stimulated RAW 264.7 cells and MsHE treatment ameliorated the rats' esophageal tissue damage induced by gastric acid and inhibited the increase of inflammatory mediators and pro-inflammatory cytokines by regulating NF-κB signaling pathway. In addition, MsHE protected the function of barrier of epithelial cells against inflammatory conditions through increasing the expression of tight junctions. Furthermore, liquid chromatography-mass spectrometry analysis was used for determine the active ingredients contained in MsHE. The results show that MsHE can alleviate experimental rat RE by regulating NF-κB signaling pathway. In summary, MsHE may be used as a source material of drug candidate for the treatment of RE.
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Esofagite Péptica/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Hexanos/química , Botões de Extremidades/química , Magnolia/química , Extratos Vegetais/química , Animais , Hexanos/uso terapêutico , Humanos , Masculino , Camundongos , RatosRESUMO
BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease, which is caused by several genetic, immunological, and environmental factors. In addition to skin manifestations, AD is associated with an increased risk of depression and suicidal ideation. Furthermore, this association is underappreciated and therefore insufficiently studied. HYPOTHESIS/PURPOSE: We investigated the association between AD and depression and the effect of I. inflexus (Thunb.) Kudo extract (IIE) treatment in a Dermatophagoides farinae extract (DfE)-induced mouse model of AD. STUDY DESIGN: We evaluated the effects of IIE on depressive behavior in AD mice using four experimental groups: normal (untreated), AD mice (untreated Dfe-induced), IIE-treated (Dfe-induced AD mice), and positive control (tacrolimus-treated Dfe-induced AD mice). METHODS: An AD model was established by the application of 4% sodium dodecyl sulfate to the shaved dorsal neck skin and ears of NC/Nga mice 1 h before application of 100 mg DfE twice per week for 3 weeks. After the first week of DfE application, mice were treated with IIE every day for the remaining 2 weeks. We performed behavioral testing, histology, ELISA, and western blotting to assess depressive-like behavior and neuroinflammatory responses and to measure IgE, histamine, corticosterone, and serotonin levels. RESULTS: Compared with normal mice, AD mice showed more scratching behavior, increased ear swelling, and higher serum levels of IgE and histamine. AD mice also exhibited evidence of depressive-like behavior in the open-field and sucrose preference tests as well as altered serum corticosterone and brain serotonin concentrations. Histopathological analyses revealed increased infiltration of inflammatory cells and mast cells into the skin and ear tissue and elevated microglia activation and neuroinflammatory response in the brains of AD mice. Topical application of IIE reversed the effects of AD on scratching behavior, ear swelling, open-field locomotion, sucrose preference, and levels of IgE, histamine, corticosterone, serotonin, and inflammatory markers. Moreover, IIE treatment reduced inflammatory cytokine responses in keratinocyte cells. CONCLUSION: IIE is a candidate anti-AD therapy due to its ability to exert neuroprotective and antidepressant effects.
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Depressão/tratamento farmacológico , Dermatite Atópica/tratamento farmacológico , Dermatophagoides farinae/química , Isodon/química , Extratos Vegetais/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Linhagem Celular , Corticosterona/sangue , Citocinas/metabolismo , Depressão/etiologia , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/psicologia , Modelos Animais de Doenças , Histamina/sangue , Humanos , Imunoglobulina E/sangue , Queratinócitos/efeitos dos fármacos , Masculino , Mastócitos/efeitos dos fármacos , Camundongos , Extratos Vegetais/química , Pele/efeitos dos fármacos , Pele/patologiaRESUMO
The authors wish to make the following corrections to this paper [...].
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Reflux esophagitis (RE) is a gastrointestinal disease caused by the reflux of gastric acid and stomach contents, and it leads to esophageal damage. Therefore, it is necessary to study the improvement of esophageal damage on a RE-induced model. The present study was accomplished to demonstrate the protective effects of a dichloromethane fraction of Geranium koreanum (DGK) plant on esophageal damage in an acute RE rat model. First, we examined the potential of anti-inflammatory effects of various fractions measured by cell cytotoxicity, morphological changes and nitric oxide (NO) production on lipopolysaccharide (LPS)-induced Raw 264.7 macrophage cells. Then, to evaluate the protective effects on RE, rats were partitioned into the following groups: normal control, RE-induced control and RE rats pre-treated with DGK 100 and 200 mg/kg body weight. The esophageal mucosal ulcer ratio was measured by the Image J program and histological changes were examined using a hematoxylin and eosin staining of the esophageal mucosa. The expression of pro-inflammatory proteins, cytokines and tight junction proteins involved in the esophageal mucosal damage were investigated using Western blotting and an enzyme-linked immunosorbent assay (ELISA) kit with esophagus tissue. DGK chemical profile and phenolic contents were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). The results showed that DGK exhibited anti-inflammatory effects against LPS-stimulated cells by significantly inhibiting NO production. Additionally, the results in vivo showed that improvement effects of DGK on esophageal mucosal damage. The expression of inflammatory proteins involved in nuclear factor κB (NF-κB) signaling pathways and tight junction protein (claudin-4 and -5) were significantly decreased in esophageal mucosa. We found the potential of DGK as source of replacement therapy products for inflammatory and RE disease.
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Anti-Inflamatórios/uso terapêutico , Esofagite Péptica/tratamento farmacológico , Esôfago/patologia , Geranium/química , Cloreto de Metileno/química , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida , Claudinas/metabolismo , Esofagite Péptica/patologia , Esôfago/efeitos dos fármacos , Inflamação/complicações , Inflamação/patologia , Lipopolissacarídeos , Camundongos , Mucosa/efeitos dos fármacos , Mucosa/patologia , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/farmacologia , Polifenóis/análise , Células RAW 264.7 , Ratos , Espectrometria de Massas em Tandem , Junções Íntimas/metabolismoRESUMO
Reflux esophagitis (RE) is a kind of gastroesophageal reflux disease, of which an esophageal inflammatory lesion is caused by the contents of the stomach and duodenum flowing back into the esophagus. Allium hookeri is a plant possessing both nutritional and medicinal properties. In our study, we investigated the inhibition effect of inflammation of A. hookeri root extract (AHE) on inflammatory RAW264.7 macrophage cells induced by lipopolysaccharide and rat models of RE. The results showed that AHE significantly reduced the production of nitric oxide (NO) and the protein expression levels of various mediators related to inflammation including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines such as interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α). Furthermore, AHE also inhibited the nuclear translocation of nuclear factor kappa B (NF-κB) by inhibiting the phosphorylation IκBα. In addition, AHE administration significantly ameliorated esophageal mucosal damage upon histological evaluation of RE in rats. AHE was also found to downregulate the expression levels of proteins such as COX-2, TNF-α, and IL-1ß in the rat esophagus. AHE markedly attenuated activation of NF-κB and phosphorylation of IκBα at the same time. These results indicated that AHE suppressed LPS-induced inflammatory responses in RAW264.7 cells and may help reduce the development of esophagitis through the modulation of inflammation by regulating NF-κB activation.
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Ulcerative colitis (UC) is a major inflammatory bowel disease (IBD) has become a worldwide emergent disease. Veronica polita (VP) is a medicinal herb that has strong antioxidant and anti-inflammatory properties. In the present study, we studied the protective effect of VP on dextran sulfate sodium (DSS)-induced experimental colitis in mice. Phytochemical screening of VP extract demonstrated the presence of high total phenolic and flavonoid contents. Compared with the DSS group, VP significantly reduced clinical symptoms with less weight loss, bloody stool, shortening of the colon, and the severity of colitis was considerably inhibited as evidenced by the reduced disease activity index (DAI) and degree of histological damage in the colon and spleen. Also, treatment with VP considerably decreased the nitric oxide (NO) and malondialdehyde (MDA) level. VP remarkably downregulated the expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), inducible nitric oxide synthetase (iNOS) and cyclooxygenase-2 (COX-2) in the colon tissue. Likewise, activation of the signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-κB) was effectively blocked by VP. Taken together, these results demonstrate that VP has an ameliorative effect on colonic inflammation mediated by modulation of oxidative stress and inflammatory mediators by suppressing the JAK2/STAT3 and NF-κB signaling pathways.
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Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Janus Quinase 2/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Veronica/química , Animais , Anti-Inflamatórios/isolamento & purificação , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Transdução de SinaisRESUMO
Globally, gastric ulcer is a vital health hazard for a human. Rabdosia inflexa (RI) has been used in traditional medicine for inflammatory diseases. The present study aimed to investigate the protective effect and related molecular mechanism of RI using lipopolysaccharide (LPS)-induced inflammation in RAW 246.7 cells and HCl/EtOH-induced gastric ulcer in mice. We applied 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), nitric oxide (NO), reactive oxygen species (ROS), histopathology, malondialdehyde (MDA), quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry (IHC), and Western blot analyses to evaluate the protective role of RI. Study revealed that RI effectively attenuated LPS-promoted NO and ROS production in RAW 246.7 cells. In addition, RI mitigated gastric oxidative stress by inhibiting lipid peroxidation, elevating NO, and decreasing gastric inflammation. RI significantly halted elevated gene expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), inducible nitric oxide synthetase (iNOS), and cyclooxygenase-2 (COX-2) in gastric tissue. Likewise, RI markedly attenuated the mitogen-activated protein kinases (MAPKs) phosphorylation, COX-2 expression, phosphorylation and degradation of inhibitor kappa B (IκBα) and activation of nuclear factor kappa B (NF-κB). Thus, experimental findings suggested that the anti-inflammatory and gastroprotective activities of RI might contribute to regulating pro-inflammatory cytokines and MAPK/NF-κB signaling pathways.
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Antioxidantes/uso terapêutico , Isodon/química , Sistema de Sinalização das MAP Quinases , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo , Mucosa Gástrica/efeitos dos fármacos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Peroxidação de Lipídeos , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Úlcera Gástrica/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Sigesbeckia pubescens (SP) is a traditional Chinese medicine, possessing antioxidant and anti-inflammatory activities. In this study, we evaluate the neuroprotective activities of SP extract on glutamate-induced oxidative stress in HT22 cells and the molecular mechanism underlying neuroprotection. We applied 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), crystal violet, reactive oxygen species (ROS), lactate dehydrogenase (LDH), quantitative real-time polymerase chain reaction (qPCR), and western blot analyses for assessing the neuroprotective effects of SP extract. The experimental study revealed that SP considerably increased the cell viability, and reduced the oxidative stress promoted ROS and LDH generation in HT22 cells in a dose-dependent manner. Additionally, the morphology of HT22 cells was effectively improved by SP. Upregulated gene expressions of mitogen-activated protein kinase (MAPK) were markedly attenuated by SP. Similarly, SP notably suppressed the ROS-mediated phosphorylation of MAPK (pERK1/2, pJNK, and pp38) cascades and activation of apoptotic factor caspase-3 signaling pathway that overall contributed to the neuroprotection. Taken together, SP may exert neuroprotective effects via alteration of MAPK and caspase-3 pathways under oxidative stress condition. Therefore, SP is a potential agent for preventing oxidative stress-mediated neuronal cell death.
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Caspase 3/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Ácido Glutâmico/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , Fármacos Neuroprotetores/isolamento & purificação , Estresse Oxidativo/fisiologiaRESUMO
Geranium koreanum (GK) is an indigenous Chinese herbal medicine widely used for the treatment of various inflammation and liver disorders. However, the exact mechanism of action of GK remains unknown. This study aimed to investigate the protective effect and related molecular mechanism of GK on NaAsO2-induced cytotoxicity in HepG2 cells and liver damage in mice. The cytoprotective role of GK was assessed on HepG2 cells using MTT assay. Oxidative stress and lactate dehydrogenase levels were measured with ROS and LDH assay. Histopathology and serum enzymes levels were estimated. The molecular mechanism was evaluated by qPCR and immunoblotting to ensure the hepatoprotective role of GK against NaAsO2 intoxication in mice. We found cotreatment with GK significantly attenuated NaAsO2-induced cell viability loss, intracellular ROS, and LDH release. Hepatic histopathology and serum biochemical parameters, ALT, and AST were notably improved by cotreatment with GK. Beside, GK markedly altered both mRNA and protein expression level of MAPK. The proapoptotic and antiapoptotic protein Bax/Bcl-2 ratio was significantly regulated by GK. Moreover, GK remarkably suppressed the postapoptotic transcription protein cleaved caspase-3 expression. The present study reveals that GK possesses hepatoprotective activity which is probably involved in the modulation of the MAPK/caspase-3 pathway.
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Sodium arsenite (NaAsO2) has been recognized as a worldwide health concern. Hydrangea macrophylla (HM) is used as traditional Chinese medicine possessing antioxidant activities. The study was performed to investigate the therapeutic role and underlying molecular mechanism of HM on NaAsO2-induced toxicity in human liver cancer (HepG2) cells and liver in mice. The hepatoprotective role of HM in HepG2 cells was assessed by using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT), reactive oxygen species (ROS), and lactate dehydrogenase (LDH) assays. Histopathology, lipid peroxidation, serum biochemistry, quantitative real-time polymerase chain reaction (qPCR) and Western blot analyses were performed to determine the protective role of HM against NaAsO2 intoxication in liver tissue. In this study, we found that co-treatment with HM significantly attenuated the NaAsO2-induced cell viability loss, intracellular ROS, and LDH release in HepG2 cells in a dose-dependent manner. Hepatic histopathology, lipid peroxidation, and the serum biochemical parameters alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were notably improved by HM. HM effectively downregulated the both gene and protein expression level of the mitogen-activated protein kinase (MAPK) cascade. Moreover, HM well-regulated the Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl-2) ratio, remarkably suppressed the release of cytochrome c, and blocked the expression of the post-apoptotic transcription factor caspase-3. Therefore, our study provides new insights into the hepatoprotective role of HM through its reduction in apoptosis, which likely involves in the modulation of MAPK/caspase-3 signaling pathways.
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Arsenitos/toxicidade , Caspase 3/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Hydrangea/química , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Compostos de Sódio/toxicidade , Alanina Transaminase/metabolismo , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Células Hep G2 , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: Rhei Rhizoma has been widely used as a traditional herbal medicine to treat various inflammatory diseases. The present study was conducted to evaluate its anti-inflammatory activity against experimental reflux-induced esophagitis (RE) in SD rats. METHODS: Rhei Rhizoma was administered at 125 or 250 mg/kg body weight per day for 7 days prior to the induction of reflux esophagitis, and its effect was compared with RE control and normal rats. RESULTS: Rhei Rhizoma administration markedly ameliorated mucosal damage on histological evaluation. The elevated reactive oxygen species in the esophageal tissue of RE control rats decreased with the administration of Rhei Rhizoma. RE control rats exhibited the down-regulation of antioxidant-related proteins, such as nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression levels, in the presence of esophagitis; however, the levels with Rhei Rhizoma treatment were significantly higher than those in RE control rats. Moreover, RE control rats exhibited the up-regulation of protein expressions related to oxidative stress in the presence of esophagitis, but Rhei Rhizoma administration significantly reduced the expression of inflammatory proteins through mitogen-activated protein kinase (MAPK)-related signaling pathways. The protein expressions of inflammatory mediators and cytokines by nuclear factor-kappa B (NF-κB) activation were modulated through blocking the phosphorylation of inhibitor of nuclear factor kappa B (IκB)α. CONCLUSION: Our findings support the therapeutic evidence for Rhei Rhizoma ameliorating the development of esophagitis via regulating inflammation through the activation of the antioxidant pathway.
Assuntos
Esofagite Péptica/prevenção & controle , Fitoterapia , Substâncias Protetoras/uso terapêutico , Rheum/química , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Biomarcadores/metabolismo , Esofagite Péptica/patologia , Esôfago/metabolismo , Mucosa Gástrica/metabolismo , Refluxo Gastroesofágico/prevenção & controle , Concentração de Íons de Hidrogênio , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
This study was performed to investigate the effects of berberine (BB) in a rat model of gastroesophageal reflux disease (GERD), induced by pylorus and forestomach ligation. We evaluated cytotoxicity and proinflammatory biomarkers (nitric oxide, interleukin (IL)-1ß and prostaglandin E2) in RAW 264.7 cells in vitro and anti-inflammatory effects in vivo. A total of 54 Sprague Dawley rats were divided into six groups: intact control rats; reflux esophagitis (RE) control rats; RE rats treated with 20 mg/kg omeprazole and RE rats treated with BB at doses of 20, 40 and 60 mg/kg, respectively. All rats were fasted. RE was induced by pylorus and forestomach ligation one hour subsequent to the oral treatment. Six hours subsequent to the surgery, the rats were sacrificed, blood was collected from the abdominal vein and the esophagus and stomach were dissected. The gastric volume and the pH of the gastric juice were evaluated, prior to the esophagus being cut longitudinally and an inner mucosal area being imaged, to analyze mucosal damage indices. Proinflammatory biomarkers in the serum, including tumor necrosis factor (TNF)-α, IL-1ß, IL-6 and monocyte chemoattractant protein (MCP)-1 were analyzed using an enzyme-linked immunosorbent assay (ELISA) kit, while the mRNA expression of TNF-α, IL-1ß, IL-6 and plasminogen activator inhibitor (PAI)-1 was analyzed using a quantitative polymerase chain reaction (qPCR). Esophagic tissue damage in the BB groups was dose-dependently decreased compared with that in the RE control group. This result was consistent with significant reductions in the levels of proinflammatory biomarkers in the serum and in the expression of proinflammatory mRNA, specifically, TNF-α, IL-1ß, IL-6 and PAI-1. The results suggest that the anti-inflammatory and protective effects of BB may attenuate the severity of RE and prevent esophageal mucosal damage, in addition to validating the use of BB as a pharmacological treatment for esophageal reflux disease.
RESUMO
Glehnia littoralis (Umbelliferae) is a traditional medicine used in Korea, China, and Japan to treat the immune-related diseases. However, its anti-inflammatory activities and mechanisms remain to be defined. We investigated the effects of 70% ethanolic extract from G. littoralis (GLE) on skin inflammation in mice. Production of proinflammatory cytokines (IL-1ß and TNF-α), activation of myeloperoxidase (MPO), and histological indicators were examined in acute and chronic skin inflammation using 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema. We also performed acetic acid-induced vascular permeability tests. GLE treatment at 200 mg/kg inhibited topical edema in the mouse ear, leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated MPO activity, and several histopathological indicators. Furthermore, GLE effectively reduced inflammatory damage induced by chronic TPA exposure and significantly inhibited the vascular permeability induced by acetic acid in mice. These results suggest that G. littoralis is an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis and may have therapeutic potential in a variety of immune-related cutaneous diseases.