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Aruncus spp. has been used as a traditional folk medicine worldwide for its anti-inflammatory, hemostatic, and detoxifying properties. The well-known species A. dioicus var. kamtschaticus has long been used for multifunctional purposes in Eastern Asia. Recently, it was reported that its extract has antioxidant and anti-diabetic effects. In this respect, it is likely that other Aruncus spp. possess various biological activities; however, little research has been conducted thus far. The present study aims to biologically identify active compounds against diabetes in the Korean endemic plant A. aethusifolius and evaluate the underlying mechanisms. A. aethusifolius extract enhanced glucose uptake without toxicity to C2C12 cells. A bioassay-guided isolation of A. aethusifolius yielded two pure compounds, and their structures were characterized as glycolipid derivatives, gingerglycolipid A, and (2S)-3-linolenoylglycerol-O-ß-d-galactopyranoside by an interpretation of nuclear magnetic resonance and high-resolution mass spectrometric data. Both compounds showed glucose uptake activity, and both compounds increased the phosphorylation levels of insulin receptor substrate 1 (IRS-1) and 5'-AMP-activated protein kinase (AMPK) and protein expression of peroxisome proliferator-activated receptor γ (PPARγ). Gingerglycolipid A docked computationally into the active site of IRS-1, AMPK1, AMPK2, and PPARγ (-5.8, -6.9, -6.8, and -6.8 kcal/mol).
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The effects of the Cichorium intybus root extract (Cii) on alcohol-induced liver disease were investigated using Chang liver cells and male Sprague Dawley rats. Silymarin, a liver-protective agent, was used as a positive control. In cell experiments, after 24 h of treatment with the extract, no cytotoxicity was noted, and death by alcohol was avoided. Migration of Chang liver cells increased after exposure to the extract at a concentration of 400 µg/mL. In animal experiments, alcohol was injected into 6-week-old rats for 1, 3, and 50 days. Oral administration of the drug was performed 30 min before alcohol administration. The control was treated with distilled water, and the drug groups were administered EtOH (40% EtOH + 2.5 mL/kg), EtOH + Cii L (low concentration, 2 mg/kg), EtOH + Cii H (high concentration, 10 mg/kg), or EtOH + silymarin (100 mg/kg). Increased liver weight was observed in the alcohol group, as were increased blood-alcohol concentration and liver damage indicators (glutamic oxalacetic transaminase (GOT), glutamic pyruvate transaminase (GPT), and triglycerides (TG)), decreased alcoholysis enzymes (ADH and ALDH), and increased CYP2E1. In the Cii treatment group, liver weight, blood-alcohol concentration, liver damage indicators (GOT, GPT, and TG), and CYP2E1 were decreased, while alcoholysis enzymes (ADH and ALDH) were increased. The degree of histopathological liver damage was compared visually and by staining with hematoxylin and eosin and oil red O. These results indicated that ingestion of Cii inhibited alcohol-induced liver damage, indicating Cii as a useful treatment for alcohol-induced liver injury.
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ETHNOPHARMACOLOGICAL RELEVANCE: Actinidia arguta (A. arguta) has been widely used in Asian countries as a traditional medicinal herb to treat inflammation-related diseases, such as gastritis, bronchitis, and arthritis. AIM OF THE STUDY: The inhibitory effect of A. arguta leaves' extract (AA) on inflammasome activation was investigated to verify its traditional use in treating inflammation-related diseases. MATERIALS AND METHODS: Bone marrow-derived macrophages (BMDMs) primed by lipopolysaccharide (LPS) were activated by selective inflammasome stimulators, and the effect of AA on inflammasome activation was investigated. A monosodium urate crystal (MSU)-induced peritonitis mouse model was used to study the in vivo efficacy of AA on inflammasome activation. RESULTS: In the in vitro study, AA regulated NLRP3 ubiquitination and apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, leading to the inhibition of NLRP3 inflammasome-mediated interleukin (IL)-1ß secretion. The inhibitory effect of AA on inflammasome activation in vitro was further confirmed in vivo using an MSU-induced peritonitis mouse model. CONCLUSION: AA provided scientific evidence, substantiating the traditional claims for its use in the treatment of inflammation and inflammation-mediated metabolic disorders, including gout.
Assuntos
Actinidia , Anti-Inflamatórios/farmacologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Caspase 1/metabolismo , Células Cultivadas , Feminino , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Peritonite/metabolismo , Extratos Vegetais/uso terapêutico , Folhas de Planta , Ubiquitinação , Ácido ÚricoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia (C. cassia, Lauraceae family), commonly used for treating dyspepsia, gastritis, blood circulation, and inflammatory diseases is considered as one of the 50 fundamental herbs in traditional Chinese medicine. AIM OF THE STUDY: The anti-inflammatory action of an ethanol extract of C. cassia (CA), and its underlying mechanisms were explored in both in vitro cellular and in vivo murine models. MATERIALS AND METHODS: Bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of CA on inflammasome activation. A lipopolysaccharide (LPS)-induced sepsis mouse model and a monosodium urate (MSU)-induced gout model were employed to study the effect of CA on in vivo efficacy. RESULTS: CA improved the survival rate in the LPS-induced septic shock mouse model and inhibited inflammasome activation including NLRP3, NLRC4, and AIM2, leading to suppression of interleukin-1ß secretion. Further, ASC oligomerization and its speck formation in cytosol were attenuated by CA treatment. Furthermore, CA improved both survival rate of LPS-induced septic shock and gout murine model. CONCLUSIONS: CA treatment significantly attenuated danger signals-induced inflammatory responses via regulation of inflammasome activation, substantiating the traditional claims of its use in the treatment of inflammation-related disorders.
Assuntos
Cinnamomum aromaticum/química , Medicamentos de Ervas Chinesas/farmacologia , Inflamassomos/efeitos dos fármacos , Animais , Medicamentos de Ervas Chinesas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Gota , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sepse/induzido quimicamente , Sepse/tratamento farmacológicoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Juniperus rigida Sieb. (J. rigida) is used for medicinal purposes in Asian countries to treat inflammation-related disorders, such as neuralgia, dropsy, and gout. AIM OF THE STUDY: The anti-inflammatory effects of J. rigida extract (JR) and its underlying mechanisms were explored both in in vitro cell lines and in vivo metabolic disease models. MATERIAL AND METHODS: Lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages were used to study the changes in inflammatory responses in vitro. Bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of JR on inflammasome activation. The murine model for monosodium urate (MSU)-induced peritonitis and high-fat diet (HFD)-induced type 2 diabetes were employed to study the effect of JR on in vivo efficacy. RESULTS: JR suppressed the MSU-induced in vivo inflammatory response by attenuation of proinflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α). In the in vitro study, JR suppressed IL-1ß secretion via regulation of apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, leading to the inhibition of inflammasome activation. JR also inhibited the LPS-stimulated release of proinflammatory mediators, such as nitric oxide (NO), TNF-α, and IL-6 in RAW264.7 cells. The inhibitory effects of JR were mediated through the regulation of the TRIF-dependent signaling pathway from JAK1/STAT1 phosphorylation. Furthermore, JR showed inhibitory effects on HFD-induced type 2 diabetes in a mouse model through the regulation of blood glucose and serum IL-1ß. CONCLUSIONS: Our results indicate that JR attenuates both LPS-stimulated and danger-signal-induced inflammatory responses in macrophages via regulation of the key inflammatory mechanisms, providing scientific support for its traditional use in the treatment of various inflammation-related metabolic disorders.
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Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Anti-Inflamatórios/farmacologia , Diabetes Mellitus Experimental/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Hipoglicemiantes/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamação/prevenção & controle , Juniperus/química , Macrófagos/efeitos dos fármacos , Peritonite/prevenção & controle , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios/isolamento & purificação , Proteínas Reguladoras de Apoptose/metabolismo , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Proteínas Adaptadoras de Sinalização CARD , Cromatografia Líquida de Alta Pressão , Citocinas/metabolismo , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Relação Dose-Resposta a Droga , Feminino , Hipoglicemiantes/isolamento & purificação , Inflamassomos/imunologia , Inflamassomos/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Janus Quinase 1/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peritonite/induzido quimicamente , Peritonite/imunologia , Peritonite/metabolismo , Fosforilação , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Células RAW 264.7 , Fator de Transcrição STAT1/metabolismo , Ácido ÚricoRESUMO
Cymbidium has known antibacterial and antiedema activity and has been used as an ingredient in cosmetics and fragrances. The effects of Cymbidium ethanol extract (CYM) on allergic response and the underlying mechanisms of action have not been reported. Therefore, the purpose of this study was to determine the effect of CYM on allergic responses. Topical application of CYM was effective against immunoglobulin E (IgE)/dinitrophenyl-conjugated bovine serum albumin- (DNP-BSA-) induced degranulation of RBL-2H3 cells and anaphylaxis in ICR mice. An allergic dermatitis-like mouse model was used to evaluate the therapeutic potential of CYM in vivo. Continuous application of 2,4-dinitrochlorobenzene (DNCB) not only induced dermatitis in ICR mice but also aggravated the skin lesioning. However, the application of CYM decreased skin lesion severity, scratching behavior, and IgE levels. In addition, CYM downregulated the expression of the proinflammatory cytokines interleukin- (IL-) 4, IL-13, and tumor necrosis factor- (TNF-) α. Studies of signal transduction pathways showed that CYM suppressed the phosphorylation of spleen tyrosine kinase (Syk), an upstream molecule. It also inhibited the phosphorylation of Akt, phospholipase C- (PLC-) γ, and mitogen-activated protein kinase kinase kinase (MEKK). These results indicate that CYM may be effective in preventing and reducing allergic response and may have therapeutic potential as an antiallergic agent in disorders such as atopic dermatitis.
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Pterocarpus indicus Willd has been widely used as a traditional medicine to treat edema, cancer, and hyperlipidemia, but its antiallergic properties and underlying mechanisms have not yet been studied. The purpose of this study was to evaluate the antiallergic activity of Pterocarpus indicus Willd water extract (PIW) using activated mast cells and an atopic dermatitis (AD)-like mouse model. PIW decreased IgE/Ag-induced mast cell degranulation and the phosphorylation of Syk and downstream signaling molecules such as PLC-γ, Akt, Erk 1/2, JNK compared to stimulated mast cells. In DNCB-induced AD-like mice, PIW reduced IgE level in serum, as well as AD-associated scratching behavior and skin severity score. These results indicate that PIW inhibits the allergic response by reducing mast cell activation and may have clinical potential as an antiallergic agent for disorders such as AD.
Assuntos
Antialérgicos/farmacologia , Dermatite Atópica/tratamento farmacológico , Imunoglobulina E/sangue , Mastócitos/efeitos dos fármacos , Pterocarpus/química , Pele/efeitos dos fármacos , Animais , Degranulação Celular/efeitos dos fármacos , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Dinitroclorobenzeno , Modelos Animais de Doenças , Regulação da Expressão Gênica , Irritantes , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/imunologia , Masculino , Mastócitos/imunologia , Mastócitos/patologia , Camundongos , Camundongos Endogâmicos ICR , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/imunologia , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/imunologia , Fosfolipase C gama/genética , Fosfolipase C gama/imunologia , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/imunologia , Transdução de Sinais , Pele/imunologia , Pele/patologia , Quinase Syk/genética , Quinase Syk/imunologia , ÁguaRESUMO
Angiogenesis, neovascularization from pre-existing vessels, is a key step in tumor growth and metastasis, and anti-angiogenic agents that can interfere with these essential steps of cancer development are a promising strategy for human cancer treatment. In this study, we characterized the anti-angiogenic effects of Coptis japonica Makino extract (CJME) and its mechanism of action. CJME significantly inhibited the proliferation, migration, and invasion of vascular endothelial growth factor (VEGF)-stimulated HUVECs. Furthermore, CJME suppressed VEGF-induced tube formation in vitro and VEGF-induced microvessel sprouting ex vivo. According to our study, CJME blocked VEGF-induced cell cycle transition in G1. CJME decreased expression of cell cycle-regulated proteins, including Cyclin D, Cyclin E, Cdk2, and Cdk4 in response to VEGF. Taken together, the results of our study indicate that CJME suppresses VEGF-induced angiogenic events such as proliferation, migration, and tube formation via cell cycle arrest in G1.
Assuntos
Inibidores da Angiogênese/farmacologia , Coptis/química , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Neovascularização Patológica/prevenção & controle , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/isolamento & purificação , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclina D/antagonistas & inibidores , Ciclina D/genética , Ciclina D/metabolismo , Ciclina E/antagonistas & inibidores , Ciclina E/genética , Ciclina E/metabolismo , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
Skeletal muscle atrophy can be defined as a decrease of muscle volume caused by injury or lack of use. This condition is associated with reactive oxygen species (ROS), resulting in various muscular disorders. We acquired 2D and 3D images using micro-computed tomography in gastrocnemius and soleus muscles of sciatic-denervated mice. We confirmed that sciatic denervation-small animal model reduced muscle volume. However, the intraperitoneal injection of Oenothera odorata root extract (EVP) delayed muscle atrophy compared to a control group. We also investigated the mechanism of muscle atrophy's relationship with ROS. EVP suppressed expression of SOD1, and increased expression of HSP70, in both H2O2-treated C2C12 myoblasts and sciatic-denervated mice. Moreover, EVP regulated apoptotic signals, including caspase-3, Bax, Bcl-2, and ceramide. These results indicate that EVP has a positive effect on reducing the effect of ROS on muscle atrophy.
Assuntos
Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Oenothera/química , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular , Ceramidas/metabolismo , Denervação/efeitos adversos , Modelos Animais de Doenças , Regulação da Expressão Gênica , Proteínas de Choque Térmico HSP70/agonistas , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Mioblastos/citologia , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Nervo Isquiático/cirurgia , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Angiogenesis, the formation of new blood vessels, is critical for tumor growth and metastasis. Notably, tumors themselves can lead to angiogenesis by inducing vascular endothelial growth factor (VEGF), which is one of the most potent angiogenic factors. Inhibition of angiogenesis is currently perceived as one of the most promising strategies for the blockage of tumor growth. In this study, we investigated the effects of Acer tegmentosum maxim water extract (ATME) on angiogenesis and its underlying signal mechanism. We studied the antiangiogenic activity of ATME by using human umbilical vein endothelial cells (HUVECs). ATME strongly inhibited VEGF-induced endothelial cell proliferation, migration, invasion, and tube formation, as well as vessel sprouting in a rat aortic ring sprouting assay. Moreover, we found that the p44/42 mitogen activated protein (MAP) kinase signaling pathway is involved in the inhibition of angiogenesis by ATME. Moreover, when we performed the in vivo matrigel plug assay, VEGF-induced angiogenesis was potently reduced when compared to that for the control group. Taken together, these results suggest that ATME exhibits potent antiangiogenic activity in vivo and in vitro and that these effects are regulated by the extracellular regulated kinase (ERK) pathway.
Assuntos
Acer/metabolismo , Inibidores da Angiogênese/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Células Hep G2 , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Invasividade Neoplásica/patologia , Neovascularização Patológica/prevenção & controle , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Impatiens textori Miq. (I. textori, Balsaminaceae) is a traditional medicinal herb used for centuries to treat several inflammatory related skin infections and allergic disorders in Asian countries. AIM OF THE STUDY: In this study, we elucidated the effects of whole plant extracts of I. textori on inflammasome activation using in vitro and in vivo models. MATERIALS AND METHODS: LPS-stimulated murine bone marrow macrophages were used to study the regulatory effect of I. textori extract (IT) on inflammasome activation. ATP, nigericin and MSU were used as danger-associated molecules to activate the NLRP3 inflammasome. An LPS-induced acute lung injury (ALI) mouse model was used to study the in vivo effect of IT on inflammasome activation. RESULTS: IT treated at 25, 50, and 100µg/mL concentrations suppressed interleukin-1ß secretion through the attenuation of NLRP3 inflammasome activation (p<0.001 at 100µg/mL) leading to the decreased amount of ASC oligomerization and caspase-1 maturation. For the in vivo model, IT inhibited the NLRP3 expression and cell recruitment at the lung tissue in the ALI mouse model. CONCLUSION: IT exhibited potent anti-inflammatory effects via the attenuation of NLRP3 inflammasome activation supporting the traditional claims and may provide a valuable therapeutic strategy in treating various inflammation-related disorders.
Assuntos
Anti-Inflamatórios/farmacologia , Impatiens/química , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Proteínas de Transporte/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Humanos , Inflamassomos/metabolismo , Inflamação/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Medicina Tradicional , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Extratos Vegetais/administração & dosagemRESUMO
Muscle atrophy, a reduction of muscle mass, strength, and volume, results from reduced muscle use and plays a key role in various muscular diseases. In the microgravity environment of space especially, muscle atrophy is induced by muscle inactivity. Exposure to microgravity induces muscle atrophy through several biological effects, including associations with reactive oxygen species (ROS). This study used 3D-clinostat to investigate muscle atrophy caused by oxidative stress in vitro, and sciatic denervation was used to investigate muscle atrophy in vivo. We assessed the effect of Oenothera odorata root extract (EVP) on muscle atrophy. EVP helped recover cell viability in C2C12 myoblasts exposed to microgravity for 24 h and delayed muscle atrophy in sciatic denervated mice. However, the expressions of HSP70, SOD1, and ceramide in microgravity-exposed C2C12 myoblasts and in sciatic denervated mice were either decreased or completely inhibited. These results suggested that EVP can be expected to have a positive effect on muscle atrophy by disuse and microgravity. In addition, EVP helped characterize the antioxidant function in muscle atrophy.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Syneilesis palmata (Thunb.) Maxim. (S. palmata, Asteraceae) is a traditional Korean therapeutic herb widely used to treat pain, arthritis, and other symptoms. This study provides the scientific basis for the anti-inflammatory effects of S. palmata extract (SP) in both in vitro and in vivo experimental models. MATERIALS AND METHODS: Lipopolysaccharide (LPS)-stimulated murine macrophages were used to study the regulatory effect of SP on the inflammatory mediators in vitro. Bone marrow-derived macrophages were used to study the effects of SP on inflammasome activation. Escherichia coli-induced sepsis mouse model and LPS-induced endotoxin shock model were employed to study the effect of SP on in vivo efficacy. RESULTS: SP inhibited the LPS-stimulated release of proinflammatory mediators, such as nitric oxide and interleukin (IL)-6 in RAW 264.7 cells. SP treatment also attenuated IL-1ß secretion via the inhibition of NLRP3 inflammasome activation induced by monosodium urate, ATP, and nigericin. Further, SP ameliorated the severity of NLRP3 inflammasome-mediated symptoms in LPS-induced endotoxin and E. coli-induced sepsis mouse models. Mechanistic studies revealed that inhibitory effects of SP were mediated through the regulation of TRIF-dependent signaling and inflammasome activation. CONCLUSION: This study was the first to reveal mechanistic-based evidence substantiating the traditional claims of SP in the treatment of inflammation-related disorders, such as pain and arthritis.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Anti-Inflamatórios/farmacologia , Asteraceae/química , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Linhagem Celular , Escherichia coli/patogenicidade , Feminino , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Plantas Medicinais/química , Sepse/tratamento farmacológico , Sepse/metabolismo , Sepse/microbiologia , Choque Séptico/induzido quimicamente , Choque Séptico/tratamento farmacológico , Choque Séptico/metabolismoRESUMO
Angiogenesis, the process of new blood vessel formation, has been a major target for cancer therapy. Antiangiogenic herbal medicines are useful in the treatment of cancer. In this study, we found that a water extract of Cinnamomum cassia (CCWE) was a potent inhibitor of angiogenesis. In cultured human umbilical vein endothelial cells, CCWE suppressed vascular endothelial growth factor (VEGF)-induced proliferation, migration, invasion, tube formation, and intracellular signaling events such as phosphorylation of ERK, p38 and VEGFR2, and activation of matrix metalloproteinase. Furthermore, CCWE inhibited VEGF-induced vessel sprouting of rat aorta ex vivo. These findings might be of particular interest for drug development because VEGF signaling is a potential target for treatment of angiogenesis-associated diseases.
Assuntos
Inibidores da Angiogênese/farmacologia , Proliferação de Células/efeitos dos fármacos , Cinnamomum aromaticum/química , Neovascularização Fisiológica/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/isolamento & purificação , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Movimento Celular/efeitos dos fármacos , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Água , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Lysimachia clethroides Duby (LC) is a traditional medicinal herb used to treat edema, hepatitis and inflammatory diseases in China and other Asian countries. In this study, the anti-inflammatory effects of LC extract and the mechanisms underlying were explored in both in vitro cell lines and acute lung injury (ALI) animal model of inflammation in vivo. MATERIALS AND METHODS: Lipopolysaccharide (LPS)-stimulated Raw 264.7 murine macrophages were used to study the regulatory effects of LC extract on inflammatory mediators such as nitric oxide (NO) and proinflammatory cytokine expression. Western blotting or ELISA techniques were employed to estimate protein levels. RT-PCR was used for analyzing the interferon (IFN)-ß production. LPS-induced ALI mouse model in vivo was employed to study the effect of LC extract. Further high-performance liquid chromatography (HPLC) fingerprinting technique was used to evaluate the active constituents present in LC extract, compared with reference standards. RESULTS: Pre-treatment with LC extract inhibited the LPS-stimulated NO release, interleukin (IL)-1ß and IL-6 production in Raw 264.7 cells dose dependently. LC extract inhibited the LPS-stimulated IRF3 and STAT1 phosphorylation. Further, in vivo experiments revealed that LC extract suppressed the infiltration of immune cells into the lung and proinflammatory cytokine production in broncho-alveolar lavage fluid (BALF) in the LPS-induced ALI mouse model. CONCLUSIONS: Our results indicate that LC extract attenuates LPS-stimulated inflammatory responses in macrophages via regulating the key inflammatory mechanisms, providing a scientific support for its traditional use in treating various inflammatory diseases.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Extratos Vegetais/uso terapêutico , Primulaceae , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Citocinas/imunologia , Feminino , Fator Regulador 3 de Interferon/imunologia , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Macrófagos , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Óxido Nítrico/imunologia , Fitoterapia , Extratos Vegetais/farmacologia , Fator de Transcrição STAT1/imunologiaRESUMO
We investigated the effects of a Eupatorium chinense var. simplicifolium (EUC) root extract on muscle disorders and explored the underlying mechanism for oxidative stress-induced C(2)C(12) myoblast damage. An EUC pre-treatment reduced the decreased cell viability after an H2O2 treatment. The heat shock protein (HSP) 70 level increased, and the phosphorylation of Jun amino-terminal kinases (JNKs) decreased in the EUC-pre-treated C(2)C(12) myoblasts. The results of the present study demonstrate the potential benefit of a herbal medicine in treating oxidative stress-related muscle disorders.
Assuntos
Apoptose/efeitos dos fármacos , Eupatorium/química , Mioblastos/citologia , Mioblastos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Linhagem Celular , Mioblastos/metabolismo , Estresse Oxidativo/efeitos dos fármacosRESUMO
Carpesium macrocephalum (CM) Fr. et Sav. (Compositae) has been used in Chinese folk medicine as an analgesic, hemostatic, antipyretic, and to suppress inflammatory conditions. In the present study we aimed to provide scientific evidence for the anti-inflammatory properties of CM extract and evaluate the intrinsic mechanisms involved in both in vitro and in vivo experimental models. In in vitro findings, CM significantly inhibited the LPS-stimulated release of proinflammatory mediators such as nitric oxide, tumor necrosis factor-alpha, prostaglandin E2, and interleukin-6 in RAW264.7 macrophages in a concentration-dependent fashion. The attenuation of inflammatory responses in LPS-activated RAW264.7 cells by CM was closely associated with the suppression of nuclear factor-kappa B (NF-κB) phosphorylation, IκB-α degradation, and phosphorylation of Akt. CM treatment also attenuated the phosphorylation of STAT through TRIF dependent pathways in LPS-activated RAW264.7 cells. In vivo studies revealed that CM extract concentration dependently suppressed the acetic acid-induced vascular permeability in mice. Considering the data obtained regulation of multiple signaling mechanisms involving TRIF and Akt/NF-κB pathways might be responsible for the potent anti-inflammatory action of CM, substantiating its traditional use in inflammatory diseases.
Assuntos
Asteraceae , Permeabilidade Capilar/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Dinoprostona/imunologia , Endotoxinas/imunologia , Endotoxinas/toxicidade , Proteínas I-kappa B/efeitos dos fármacos , Proteínas I-kappa B/metabolismo , Interleucina-6/imunologia , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/toxicidade , Macrófagos/imunologia , Camundongos , Inibidor de NF-kappaB alfa , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Óxido Nítrico , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição STAT/efeitos dos fármacos , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/imunologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Cell injury associated with reactive oxygen species (ROS) has been reported in various muscular disorders. We found that a Cichorium intybus (Cii) extract reduced H(2)O(2)-induced viability loss in C2C12 myoblasts, inhibited oxidative stress-induced apoptosis and increased intracellular heat shock protein 70 (Hsp 70) expression. Cii also inhibited the level of intracellular ceramide. These results indicate that Cii may prevent skeletal muscle atrophy by inducing the expression of Hsp 70 and inhibiting the level of ceramide.
Assuntos
Antioxidantes/farmacologia , Cichorium intybus/química , Mioblastos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Acetilcisteína/farmacologia , Animais , Antioxidantes/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ceramidas/antagonistas & inibidores , Ceramidas/biossíntese , Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Peróxido de Hidrogênio/farmacologia , Camundongos , Mioblastos/citologia , Mioblastos/metabolismo , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismoRESUMO
Inflammation is a system used by a host to defend against the presence of bacteria, viruses, or yeasts. Toll-like receptors (TLRs) in the plasma membranes of macrophages are activated when they recognize the molecular structure of a virus or bacterium. Lipopolysaccharide (LPS), an outer cell-wall component of Gram-negative bacteria, initiates an inflammatory process via TLR4. We investigated the effect of the extract of Anethum graveloens flowers (AGFs) on LPS-mediated inflammation in RAW 264.7 cells. The extract markedly suppressed nitric oxide generation in a concentration-dependent manner in LPS-stimulated RAW 264.7 cells. It inhibited inducible nitric oxide synthase (iNOS) and the mRNA expression of cytokines such as interleukin-1 beta and interleukin-6 in LPS-stimulated RAW 264.7 cells. It also inhibited iNOS protein levels in LPS-stimulated RAW 264.7 cells. In addition, AGF decreased the LPS-induced phosphorylation of mitogen-activated protein kinases in LPS-stimulated RAW 264.7 cells. AGF inhibited the phosphorylation of Akt, an upstream molecule of the nuclear factor kappa B (NF-κB) pathway, and thus inhibited NF-κB activity in LPS-stimulated RAW 264.7 cells. These results suggest that AGF exerts an anti-inflammatory effect in LPS-stimulated RAW 264.7 cells by inhibiting iNOS expression and blocking the NF-κB pathway.
Assuntos
Anethum graveolens/química , Anti-Inflamatórios não Esteroides/farmacologia , Macrófagos/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Animais , Anti-Inflamatórios não Esteroides/isolamento & purificação , Linhagem Celular , Relação Dose-Resposta a Droga , Flores/química , Expressão Gênica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/genética , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL EVIDENCE: Agrimonia pilosa Ledeb (Rosaceae, AP) has long been used as a traditional medicine in Korea and other Asian countries to treat various diseases. AIM OF THE STUDY: In the present study, the anti-inflammatory and anti-allergic effects of AP extract in in vitro cell lines and in vivo mouse model of inflammation and the molecular mechanisms involved were reported. MATERIALS AND METHODS: Using Raw 264.7 murine macrophages the effects of methanol extract of AP in lipopolysaccharide (LPS)-induced production of inflammatory mediators were measured. Further IgE-DNP-induced interleukin (IL)-4 production and degranulation in RBL-2H3 rat basophilic cell lines was also estimated. To investigate the anti-asthmatic effect of AP in vivo, airway inflammation in ovalbumin (OVA)-induced mouse model was used. RESULTS: AP attenuated the production of inflammatory mediators such as NO, PGE(2) and pro-inflammatory cytokines in LPS-induced Raw 264.7 cells. Further, AP inhibited IL-4 production and degranulation in IgE-DNP-induced RBL-2H3 cells. Furthermore, AP attenuated the infiltration of immune cells into lung, cytokines production in broncho-alveolar lavage fluid (BALF) and airway-hyperresponsiveness (AHR) on OVA-induced mouse model of inflammation. CONCLUSION: Our results showed that AP attenuated the activation of macrophages, basophils, and inhibited the OVA-induced airway inflammation. The molecular mechanisms leading to AP's potent anti-inflammatory and anti-allergic effects might be through regulation of TRIF-dependent and Syk-PLCγ/AKT signaling pathways, suggesting that AP may provide a valuable therapeutic strategy in treating various inflammatory diseases including asthma.