RESUMO
Wheat (Triticum aestivum L.) is the oldest known food crop, and many studies have reported that wheat shoots (i.e., wheatgrass) possess anti-cancer, anti-inflammatory, and antioxidant activities. However, the potentially ameliorative effect of wheat shoots on hepatotoxicity caused by high doses of N-acetyl-para-aminophenol (acetaminophen, APAP) has yet to be reported. C57BL/6 mice received daily oral TAE (100 or 200 mg/kg), positive control (silymarin 100 mg/kg), or negative control (saline vehicle) treatments for 7 days prior to intraperitoneal APAP injection. Histological, serum (ELISA), Western blotting, and quantitative PCR analyses of excised liver tissues were then performed. Pre-treatment with TAE (100 or 200 mg/kg) ameliorated APAP-induced pathological damage (i.e., hepatotoxic lesions), reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and also ameliorated APAP-induced increases in oxidative stress, thereby inhibiting oxidative liver damage and reducing the expression of inflammatory cytokines. In addition, TAE pre-treatment inhibited the expression of Cytochrome P4502E1 (CYP2E1), which is a key enzyme in the onset of APAP-induced hepatotoxicity, suppressed the expression of the target proteins regulated by the antioxidant enzyme Nrf2, and suppressed hepatocyte apoptosis. These findings suggest that TAE is an attractive therapeutic candidate that exhibits potential hepatoprotective activity by inhibiting oxidative stress, inflammation, apoptosis, and liver damage.
Assuntos
Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Triticum/química , Acetaminofen/efeitos adversos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Apoptose/efeitos dos fármacos , Biomarcadores , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Citocromo P-450 CYP2E1/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Testes de Função Hepática , Masculino , Camundongos , Estrutura Molecular , Fator 2 Relacionado a NF-E2 , Extratos Vegetais/química , Substâncias Protetoras , Transdução de Sinais/efeitos dos fármacosRESUMO
Background and objectives: Blood vessel thrombosis causes blood circulation disorders, leading to various diseases. Currently, various antiplatelet and anticoagulant drugs, such as aspirin, warfarin, heparin, and non-vitamin K antagonist oral anticoagulants (NOACs), are used as the major drugs for the treatment of a wide range of thrombosis. However, these drugs have a side effect of possibly causing internal bleeding due to poor hemostasis when taken for a long period of time. Materials and Methods: Gastrodia elata Blume (GE) and Zanthoxylum schinifolium Siebold & Zucc (ZS) are known to exhibit hemostatic and antiplatelet effects as traditional medicines that have been used for a long time. In this study, we investigated the effect of a mixed extract of GE and ZS (MJGE09) on platelet aggregation and plasma coagulation. Results: We found that MJGE09 inhibited collagen-and ADP-induced platelet aggregation in vitro. In addition, collagen- and ADP-induced platelet aggregation were also inhibited in a dose-dependent manner on the platelets of mice that were orally administered MJGE09 ex vivo. However, compared with aspirin, MJGE09 did not prolong the rat tail vein bleeding time in vivo and did not show a significant effect on the increase in the prothrombin time (PT) and activated partial thromboplastin time (aPTT). Conclusions: These results suggest that MJGE09 can be used as a potential anticoagulant with improved antithrombotic efficacy.
Assuntos
Gastrodia , Trombose , Zanthoxylum , Administração Oral , Animais , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Agregação Plaquetária , Inibidores da Agregação Plaquetária/farmacologia , Ratos , Ratos Sprague-Dawley , Trombose/tratamento farmacológicoRESUMO
When skin is exposed to UV radiation, melanocytes produce melanin. Excessive melanin production leads to skin pigmentation, which causes various cosmetic and health problems. Therefore, the development of safe, natural therapeutics that inhibit the production of melanin is necessary. Elaeagnus umbellata (EU) has long been widely used as a folk medicinal plant because of pharmacological properties that include anti-ulcer, antioxidant, and anti-inflammatory properties. In this study, we investigated the antioxidant activity and melanogenesis inhibitory effects of EU fractions in B16-F10 melanoma cells. EU fractions showed a dose-dependent increase in antioxidant activity in radical scavenging activity. In addition, we evaluated the effect of EU fractions on tyrosinase activity and melanogenesis in α-melanocyte-stimulating hormone-induced B16-F10 melanoma cells. EU was noncytotoxic at 12.5-50 µg/mL. EU fractions effectively inhibited tyrosinase activity and melanogenesis, suppressed the phosphorylation of CREB and ERK involved in the melanogenesis pathway, and down-regulated expression of melanogenesis-related proteins. Interestingly, the anti-melanogenesis effect was most effective at a concentration of 50 µg/mL EU, and the effects of the fractions were superior to those of the extract. Therefore, our study suggests that EU has potential as a safe treatment for excessive pigmentation or as a natural ingredient in cosmetics.
Assuntos
Elaeagnaceae/química , Melaninas/metabolismo , Melanócitos/citologia , Melanoma Experimental/tratamento farmacológico , Monofenol Mono-Oxigenase/antagonistas & inibidores , Extratos Vegetais/farmacologia , alfa-MSH/farmacologia , Animais , Antioxidantes/farmacologia , Sobrevivência Celular , Hormônios/farmacologia , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Melanoma Experimental/patologia , Camundongos , Fosforilação , Pigmentação da Pele/efeitos dos fármacosRESUMO
BACKGROUND: Nodakenin, a coumarin glucoside isolated from the roots of Angelica biserrata, has been reported to have anti-inflammatory, antibacterial, anticancer effects. However, despite these studies, the potential liver protective effects of nodakenin in inflammatory liver injury models have not been reported. METHODS: A mouse model of inflammatory liver injury was induced by injection of lipopolysaccharide (LPS) (15 mg/kg, intraperitoneally (i.p)). Liver tissue AST, ALT, ROS, T-GSH and T-SOD were analyzed by ELISA. The concentrations of TNF-α, IL-6, and IL-1ß in serum of LPS-induced inflammatory liver injury mice were analyzed. The mRNA expression levels of GPx1, catalase, SOD1, SOD2, TNF-α, IL-6, IL-1ß, iNOS and COX-2 were analyzed using real-time PCR. The expressions of MAPK, IRF3, NF-κB, Nrf2, HO-1, caspase-3 and caspase-7 were analyzed using western blotting. Liver tissue was stained with IHC to confirm NF-κB, Nrf-2, HO-1, caspase-3, Bax, and Bcl2. Tunnel analysis was performed to confirm the fragmented nuclear DNA characteristics of apoptosis. RESULTS: The administration of nodakenin (10 and 30 mg/kg) reduced serum aminotransferase levels compared to LPS-induced liver damage and significantly improved the oxidative state of liver tissue and pathological damage. Moreover, inhibited the phosphorylation of transforming growth factor beta (TGF-ß)-activated kinase (TAK)-1 in LPS-induced inflammatory liver injury model, and significantly inhibited the transcriptional of nuclear factor-kappa B (NF-kB) and the secretion of pro-inflammatory mediators. In addition nodakenin pre-treatment also attenuated hepatocyte death by regulating apoptosis-related mitochondrial proteins, such as cysteinyl aspartate specific proteinase 3 (caspase 3), poly (ADP-ribose) polymerase (PARP), B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). CONCLUSION: Our findings suggest that nodakenin has anti-inflammatory, anti-oxidant and anti-apoptotic activity and may be an adjunctive prevention agent for liver injury.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Cumarínicos/farmacologia , Glucosídeos/farmacologia , Hepatite Animal/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/sangue , Citocinas/genética , Enzimas/metabolismo , Hepatite Animal/metabolismo , Hepatite Animal/patologia , Masculino , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologiaRESUMO
Mast cells are effector cells that initiate allergic inflammatory immune responses by inducing inflammatory mediators. Boehmeria nivea (Linn.) Gaudich is a natural herb in the nettle family Urticaceae that possesses numerous pharmacological properties. Despite the various pharmacological benefits of Boehmeria nivea, its effects on allergic inflammation have not yet been determined. Here, we investigated the effect of the ethanol extract of Boehmeria nivea (BNE) on degranulation rat basophilic leukemia (RBL)-2H3 mast cells stimulated with anti-dinitrophenyl (anti-DNP) and bovine serum albumin (BSA) during immunoglobulin E (IgE)-mediated allergic immune response. The results showed inhibition of the release of ß-hexosaminidase and histamine from the cells. BNE suppressed pro-inflammatory cytokines (Tumor necrosis factor (TNF)-α, Interleukin (IL)-1ß, and IL-6) and reduced T helper (Th)2 cytokine IL-4 expression and/or secretion correlated with the downregulation of p38, extracellular signal-regulated kinases (ERK) mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) signaling pathways in treated RBL-2H3 mast cells. In passive cutaneous anaphylaxis, treatment with BNE during IgE-mediated local allergic reaction triggered a reduction in mouse ear pigmentation and thickness. Taken together, these results indicated that BNE suppressed mast cell-mediated inflammation, suggesting that BNE might be a candidate for the treatment of various allergic disorders.
Assuntos
Boehmeria/química , Hipersensibilidade/tratamento farmacológico , Inflamação/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Extratos Vegetais/farmacologia , Anafilaxia/metabolismo , Animais , Antialérgicos/farmacologia , Linhagem Celular Tumoral , Citocinas/metabolismo , Histamina/química , Liberação de Histamina/efeitos dos fármacos , Imunoglobulina E/química , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Pigmentação , Folhas de Planta/química , Ratos , Soroalbumina Bovina/química , beta-N-Acetil-Hexosaminidases/químicaRESUMO
Soshiho-tang (SST) is a well-known traditional herbal medicine used for the treatment of many diseases. The aims of this study are to investigate the effects of SST on atopic dermatitis (AD) symptoms and to examine its mechanism. Human keratinocyte (HaCaT) cells were stimulated with tumor necrosis factor alpha (TNF-α)/IFN-γ to induce AD-like keratinocyte environment. 2,4-Dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in the dorsal skin of BALB/c mice. SST and dexamethasone were administered orally for 14 day. As a result, SST treatment increased the expression of heme oxygenase-1 (HO-1), an anti-oxidative factor, and the nuclear translocation of NF-E2 p45-related factor 2 (Nrf2). In addition, the treatment also decreased the expression level of inflammatory mediator nuclear factor-κB (NF-κB) and the adhesion molecule intercellular adhesion molecule-1 (ICAM-1). SST treatment (75 and 150â¯mg/kg) significantly relieved AD symptoms in DNCB-induced AD-like mice by restoring skin thickness, spleen weight, immunoglobulin E (IgE), interleukin 4 (IL-4), pro-inflammatory cytokine expression, and expression of several other mediators. We found that SST alleviates AD-like skin lesions and skin inflammation by modulating various atopic symptoms and inflammatory mediators. Therefore, SST can be used as an alternative drug for the treatment of AD.
RESUMO
Enzyme treatment of the foods and herbs has been used to improve the absorption rate the efficiency of plant extracts by converting the glycosides of the plant into aglycones. In this study, we examined the obesity-inhibitory effect of Chrysanthemum indicum Linné (CI) treated with enzymes such as viscozyme and tannase, which are highly efficient in converting glycosides to aglycones and then compared with untreated CI extract. The enzyme-treated CI ethanol extract (CIVT) was administered orally at various doses for 7 weeks in the high fat diet (HFD)-fed male mice. CIVT administration reduced the body weights, the food efficiency and the serum levels of lipid metabolism-related biomarkers, such as triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and leptin in the dose-dependent manner but not those high-density lipoprotein cholesterol (HDL-c) and adiponectin. CIVT also reduced considerably the total lipid amount in the liver and the size of adipocytes in the epididymal white adipose tissue (eWAT). CIVT effectively downregulated the adipogenesis-related transcription factors such as peroxisome proliferation activated receptor (PPAR)-γ and CCAAT/enhancer binding protein-α (C/EBP-α) but up-regulated PPAR-α, in the liver and eWAT. In addition, when compared to the enzyme-untreated CI 50% ethanol extract (CIEE), CIVT enhanced the reduction of body weight and lipid accumulation. Moreover, the viscozyme and tannase treatment of CI increased the flavonoid contents of the aglycone form. Therefore, our results support that the enzymatic treatment induced the production of aglycones for potentially suppressing the adipogenesis and lipid accumulation in HFD-fed mice. It suggests that CIVT might be an effective candidate for attenuating the over-weight and its related diseases.
Assuntos
Adipogenia/efeitos dos fármacos , Chrysanthemum/química , Dieta Hiperlipídica , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/metabolismo , Extratos Vegetais , Adipócitos/efeitos dos fármacos , Animais , Hidrolases de Éster Carboxílico/metabolismo , Fígado/citologia , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Complexos Multienzimáticos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Aumento de Peso/efeitos dos fármacosRESUMO
Chronic intestinal inflammation is critical risk factor of colorectal cancer. Triticum aestivum sprouts have been reported to provide a number of health benefits and used as a dietary supplement. In this study, the authors investigated the regulatory effects of T. aestivum sprouts ethanol extract (TAEE) on experimental colorectal carcinogenesis in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model. Oral administration of TAEE significantly attenuated crypt destruction and tumor formation in AOM/DSS-treated mice. Levels of inflammatory mediators involved in colorectal carcinogenesis, that is, tumor necrosis factor-α, interkeukin (IL)-1ß, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase, were lower in the colons of 200 mg/kg TAEE-treated mice than in AOM/DSS controls (p < 0.05). Immunohistochemical staining showed that levels of nuclear factor-kappa B p65 and ß-catenin were attenuated by TAEE in the colon tissues of AOM/DSS-treated mice. Furthermore, levels of ß-catenin-related genes (cyclin D1 and c-Myc), which are known to contribute to cell cycle regulation, were decreased in the colon tissues of TAEE-treated mice versus AOM/DSS controls (p < 0.01). These results showed TAEE inhibited colon inflammation and neoplasm formation caused by AOM/DSS treatment, suggesting that TAEE could be useful for the prevention and treatment of colitis-associated colon cancer.
Assuntos
Neoplasias do Colo/prevenção & controle , Extratos Vegetais/uso terapêutico , Triticum , Animais , Azoximetano , Neoplasias do Colo/induzido quimicamente , Sulfato de Dextrana , Mediadores da Inflamação/análise , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator de Transcrição RelA/análise , Triticum/química , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/análise , beta Catenina/fisiologiaRESUMO
BACKGROUND: Euphorbia supina (ES) has been widely used in folk medicine owing to its antibacterial, hemostatic, and anti-inflammatory properties. The aim of this study was to evaluate the antioxidant and skin-whitening effects of a 70% ethanol extract of ES. METHODS: The aerial parts of ES plant were extracted with 70% ethanol. The viability of B16F10 cells was evaluated by MTT assay to determine the non-toxic doses for further experiments. The tyrosinase and cellular tyrosinase activities were then measured using an enzyme-substrate assay. In addition, the expression of whitening-related proteins was measured using western blot. RESULTS: The antioxidant activity of the ES samples increased in a dose-dependent manner, as confirmed by their radical scavenging activities in the 2,2-diphenyl-1-1-picrylhydrazyl and 2,2-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) assays. The ES extract significantly reduced tyrosinase activity and melanin content in a dose-dependent manner. Furthermore, it decreased α-melanocyte stimulating hormone (MSH)-induced protein expression of tyrosinase and microphthalmia-associated transcription factor (MITF). CONCLUSIONS: Our results indicate that the ES extract attenuated α-MSH-stimulated melanin synthesis by modulating tyrosinase and MITF expression. Therefore, the ES extract could be a promising therapeutic agent to treat hyperpigmentation and as an ingredient for skin-whitening cosmetics.
Assuntos
Antioxidantes/farmacologia , Euphorbia/química , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Preparações Clareadoras de Pele/farmacologia , Animais , Antioxidantes/química , Linhagem Celular Tumoral , Melaninas/metabolismo , Camundongos , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Extratos Vegetais/química , Biossíntese de Proteínas/efeitos dos fármacos , Preparações Clareadoras de Pele/química , alfa-MSH/metabolismoRESUMO
BACKGROUND: Euphorbia supina (ES) plant has been used as treatment for inflammatory conditions. The antibacterial effect and the anti-inflammatory mechanism of ES for Propionibacterium (P.) acnes-induced inflammation in THP-1 cells and acne animal model remain unclear. Therefore, the objective of the present study was to determine the antibacterial and anti-inflammatory activities of ES against P. acnes, the etiologic agent of skin inflammation. METHOD: The antibacterial activities of ES were tested with disc diffusion and broth dilution methods. Cytotoxicity of ES at different doses was evaluated by the MTT assay. THP-1 cells were stimulated by heat-killed P. acnes in the presence of ES. The pro-inflammatory cytokines and mRNA levels were measured by ELISA and real-time-PCR. MAPK expression was analyzed by Western blot. The living P. acnes was intradermally injected into the ear of BLBC/c mice. Subsequently, chemical composition of ES was analyzed by liquids chromatography-mass spectrometry (LC-MS). RESULT: ES had stronger antibacterial activity against P. acnes and inhibitory activity on lipase. ES had no significant cytotoxicity on THP-1 cells. ES suppressed the mRNA levels and production of IL-8, TNF-a, IL-1ß in vitro. ES inhibited the expression levels of pro-inflammatory cytokines and the MAPK signaling pathway. Ear thickness and inflammatory cells were markedly reduced by ES treatment. Protocatechuic acid, gallic acid, quercetin, and kaempferol were detected by LC-MS analysis in ES. CONCLUSIONS: Our results demonstrate antibacterial and anti-inflammatory activities of ES extract against P. acnes. It is suggested that ES extract might be used to treatment anti-inflammatory skin disease.
Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Euphorbia/química , Inflamação/microbiologia , Extratos Vegetais/farmacologia , Propionibacterium acnes/efeitos dos fármacos , Animais , Antibacterianos/toxicidade , Anti-Inflamatórios/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Inflamação/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Extratos Vegetais/toxicidade , Pele/efeitos dos fármacos , Pele/patologiaRESUMO
Atopic dermatitis (AD) is a common chronic, recurring, inflammatory skin disease. A number of researchers have been seeking safe AD therapies for a long time. Triticum aestivum sprouts (TAEE), known as wheatgrass, are one of the most widely used health foods worldwide. They show numerous beneficial effects, including anticancer, antiinflammatory, antioxidant, antiobesity, anticolitis and antiallergy effects; however, their effect on AD is unknown. In the present study, the antiAD effects of a 70% ethanol extract of TAEE were investigated in 2,4dinitrochlorobenzene (DNCB)treated mice with ADlike skin lesions and in tumor necrosis factor (TNF)α and interferon (IFN)γstimulated human keratinocytes (HaCaT cells). Oral administration of 200 mg/kg TAEE for 10 days significantly decreased the skin thickness, transepidermal water loss and serum immunoglobulin E levels in DNCBtreated mice. In addition, TAEE reduced the secretion of inflammatory chemokines via regulation of the signal transducer and activator of transcription 1 and suppressor of cytokine signaling pathways in TNFα and IFNγstimulated HaCaT cells. These results indicate that TAEE may have beneficial effects in the treatment and prevention of AD and associated skin diseases.
Assuntos
Quimiocinas/genética , Dermatite Atópica/etiologia , Dermatite Atópica/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Extratos Vegetais/farmacologia , Plântula/química , Triticum/química , Animais , Células Cultivadas , Quimiocinas/imunologia , Citocinas/metabolismo , Dermatite Atópica/tratamento farmacológico , Dinitroclorobenzeno/efeitos adversos , Modelos Animais de Doenças , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Queratinócitos/imunologia , Camundongos , Extratos Vegetais/química , Fator de Transcrição STAT1/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The present study was undertaken to investigate the antiobesity effect of a 50% ethanol extract of Euphorbia supina (ESEE) in highfatdiet (HFD)induced obese C57BL/6J mice. Mice were fed a HFD with or without ESEE (2, 10, or 50 mg/kg) or with Garcinia cambogia (positive control) for 6 weeks. ESEE supplementation significantly reduced body, epididymal white adipose tissue (eWAT), and organ weights (P<0.05). ESEE also reduced hepatic steatosis and improved serum lipid profiles. In addition, ESEE significantly reduced serum leptin levels and increased adiponectin levels, and significantly downregulated the mRNA and protein levels of proliferatoractivated receptor γ (PPARγ) and CCAAT/enhancerbinding protein alpha (C/EPBα) in eWAT and liver tissues (all P<0.05). These results suggested that ESEE supplementation protects against HFDinduced obesity by downregulating PPARγ and C/EPBα, and that ESEE may be beneficial for the prevention and treatment of obesity and associated diseases.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Euphorbia , Obesidade/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Adipogenia/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Fármacos Antiobesidade/química , Peso Corporal/efeitos dos fármacos , Euphorbia/química , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/patologia , Extratos Vegetais/químicaRESUMO
Chrysanthemum indicum (CI) is widely distributed in China and many parts of the tropical world, and has been reported to have antibacterial, antiviral, anti-oxidant and immunomodulatory effects, but no information is available on its effects on high fat diet (HFD)-induced obesity. This was undertaken to investigate the mechanism responsible for the effect of ethyl acetate fraction of CI (CIEA) on adipogenesis, in vitro and in vivo models of obesity. In the in vitro study, differentiating 3T3-L1 cells were treated with media to initiate differentiation (MDI) in the presence or absence of CIEA with different concentrations, and in the in vivo study, C57BL/6 mice were fed with HFD and administered CIEA daily for six weeks. Garcinia cambogia (GC) was used as the positive control, and was administered in the same manner as CIEA. Results showed CIEA reduced HFD-induced body weight gain, epididymal white adipose tissue (eWAT), and liver weight. In addition, CIEA significantly decreased serum lipid profiles, including total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDLc) and increased high density lipoprotein cholesterol (HDLc) levels. Furthermore, CIEA also reduced leptin levels and increased adiponectin levels in serum, and significantly decreased peroxisome proliferator-activated receptor [Formula: see text] (PPAR[Formula: see text]) and CCAAT/enhancer-binding protein (C/EPBs) levels, but increased PPAR[Formula: see text] level and the phosphorylation of AMP-activated protein kinase (AMPK) in eWATs and in the liver tissues of HFD fed obese mice. Taken together, these results indicate CIEA might be beneficial for preventing obesity.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipogenia/efeitos dos fármacos , Chrysanthemum/química , Dieta Hiperlipídica/efeitos adversos , Obesidade/metabolismo , Obesidade/prevenção & controle , Fitoterapia , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células 3T3-L1 , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Animais , Relação Dose-Resposta a Droga , Leptina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Tamanho do Órgão/efeitos dos fármacos , PPAR gama/metabolismo , Extratos Vegetais/administração & dosagem , Aumento de Peso/efeitos dos fármacosRESUMO
Triticum aestivum sprouts (TA) contain significant amounts of chlorophyll, minerals, enzymes, and other functional entities. Furthermore, TA extracts have been shown to possess anti-obesity, anti-diabetic and hepatoprotective effects and are believed to help blood flow, digestion, and general detoxification of the body. In this study, the mechanism underlying the anti-cancer effects of a dichloromethane fraction of TA (TDF) was investigated in vitro and in vivo. In vitro study was done by examining cancer cells growth, morphological changes, cell cycles, expressions of death receptors and apoptosis-linked proteins in wide range of human cancer cell lines. To investigate the effect of TDF in vivo, C57BL/6 mice were injected with B16 melanoma cells and orally administered TDF. TDF markedly inhibited cancer cell growth and induced cellular morphological alterations, cell cycle arrest and apoptosis, and enhanced the expressions of death receptors (DR)-4, 5, and 6 in cell lines. In addition, TDF regulated the expressions mitochondrial apoptosis-linked proteins and induced caspase-dependent cell death. It also significantly enhanced phosphorylation of ERK1/2 and JNK, but not p38, whereas inhibited the activation of NF-κB in cancer cells. In our mouse model, TDF significantly suppressed B16 melanoma growth, to an extent similar to cisplatin (reference control) and augmented immunomodulatory cytokines. In brief, this study presents the mechanism responsible for the anti-cancer effects of TDF in vitro and in vivo.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Melanoma Experimental/tratamento farmacológico , Cloreto de Metileno/uso terapêutico , Extratos Vegetais/uso terapêutico , Plântula , Triticum , Células A549 , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Masculino , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Cloreto de Metileno/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologiaRESUMO
The aim of this study is to examine the anti-inflammatory effect of Euphorbia supina (ES) ethanol extract in dextran sulfate sodium (DSS)-induced experimental colitis model. ES was per orally administered at different doses of 4 or 20 mg/kg body weight with 5% DSS in drinking water for 7 days. Twenty mg/kg of ES administration regulated body weight decrease, recovered colon length shortening, and increased disease activity index score and myeloperoxidase level in DSS-induced colitis. Histological features showed that 20 mg/kg of ES administration suppressed edema, mucosal damage, and the loss of crypts induced by DSS. Furthermore, ES suppressed the expressions of COX-2, iNOS, NF-kB, IkBα, pIkBα in colon tissue. These findings demonstrated a possible effect of amelioration of ulcerative colitis and could be clinically applied.
Assuntos
Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Euphorbia/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Peso Corporal/efeitos dos fármacos , Colite/metabolismo , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Ciclo-Oxigenase 2/metabolismo , Etanol/química , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Peroxidase/metabolismo , Extratos Vegetais/uso terapêutico , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Triticum aestivum sprout-derived polysaccharide (TASP) has anti-diabetic properties, but no information is available in regards to its protective effect against ethanol-induced hepatic injury. This study aimed to investigate the mechanism behind the protective role of TASP against ethanol-induced liver injury in vivo. Male C57BL/6 mice were administered ethanol with or without TASP for 10 consecutive days by oral gavage. Silymarin was administered in the same manner as a positive control. TASP reduced ethanol-induced hepatic lipid accumulation and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. TASP also prevented glutathione (GSH) depletion and increased the superoxide dismutase (SOD) in liver tissue. In addition, TASP significantly inhibited ethanol-induced cytochrome P450 2E1 (CYP2E1) activation, and upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1), and downregulated NADPH oxidase genes in ethanol fed mice. Furthermore, the upregulation of Nrf2 was found to be regulated by a phosphatidylinositol 3-kinase (PI3K)/Akt pathway. TASP also attenuated hepatic injury by modulation of caspase-3 and apoptosis-associated mitochondrial proteins including B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) in liver tissues of mice. The study demonstrated that TASP treatment protects against ethanol-induced hepatic injury via multiple pathways by inhibiting steatosis and improving antioxidant marker levels during hepatic injury. Such properties provide a basis for therapeutic agents against alcohol-induced liver injury.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Triticum/química , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Animais , Antioxidantes/isolamento & purificação , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Etanol/administração & dosagem , Regulação da Expressão Gênica , Glutationa/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Extratos Vegetais/química , Polissacarídeos/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Plântula/química , Silimarina/farmacologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: Several intervention studies have suggested that foot massage and cognitive behavioral therapy (CBT) are beneficial for reducing the stress response. However, no randomized control trials have been conducted to examine these effects in middle-aged women, who are more commonly exposed to stress relative to others. This study aimed to examine the effects of combined self-administered foot massage and CBT on the psychophysiological stress response in Korean middle-aged women. DESIGN: Randomized controlled trial. SETTING: Subjects were recruited from the social welfare center in Sahmcheok, Kangwondo, Korea. The subjects performed some of the massage at the center and some at home, and CBT was performed at the center. SUBJECTS: Fifty-three women aged 45-64 years were randomly assigned to Group A (intervention, n = 31) or B (usual care, n = 30). INTERVENTION: Combined self-administered foot massage and CBT. OUTCOME MEASURES: Depression, anxiety, stress, blood pressure, heart rate, blood glucose (BG), and oxygen saturation were measured at baseline and 3-week follow-up. RESULTS: Mean depression scores (p = 0.021), stress scores (p = 0.009), systolic blood pressure (SBP) (p = 0.035), and BG levels (p = 0.007) had decreased significantly subsequent to the intervention. CONCLUSION: Combined self-administered foot massage and CBT led to reductions in depression, stress, SBP, and BG levels. Therefore, the intervention could be an effective means of reducing the stress response in middle-aged women.
Assuntos
Terapia Cognitivo-Comportamental , Pé/fisiologia , Massagem , Estresse Psicológico/terapia , Adulto , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Hepatic injury occurs frequently during sepsis, and polysaccharides isolated from plants have been reported to have antiinflammatory and antioxidant effects in various models. However, the effect of wheatgrass-derived polysaccharide (WGP) has not been previously studied. In the present study, we investigated the effect of WGP on lipopolysaccharide (LPS)-induced hepatic injury in mice. Mice were pre-treated with WGP (100 or 200 mg/kg daily for 2 days) and then challenged with LPS (1 mg/kg, intraperitoneal), and sacrificed after 12 h. Wheatgrass-derived polysaccharide decreased serum aminotransferase levels and histological changes as compared with LPS-challenged mice. Wheatgrass-derived polysaccharide also significantly inhibited LPS-induced pro-inflammatory cytokine up-regulation and improved the oxidative status of liver tissues. Furthermore, these effects were found to be mediated by the suppression of the transcriptional activity of nuclear factor-kappa B (NF-κB), due to inhibitions of transforming growth factor beta (TGF-ß)-activated kinase (TAK)-1 phosphorylation and inhibition of kappa B (IκB)-α degradation. In addition, WGP inhibited the activations of mitogen-activated protein kinases (MAPKs). Wheatgrass-derived polysaccharide also attenuated hepatic cell death by modulating caspase-3 and apoptosis associated mitochondrial proteins, such as, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). Taken together, WGP possesses antiinflammatory, anti-oxidant and anti-apoptotic activity and ameliorates LPS-induced liver injury in mice. Copyright © 2017 John Wiley & Sons, Ltd.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Polissacarídeos/farmacologia , Triticum/química , Animais , Caspase 3/metabolismo , Citocinas/metabolismo , Lipopolissacarídeos , Fígado/efeitos dos fármacos , Fígado/patologia , MAP Quinase Quinase Quinases/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Gastrodia elata Blume (GE) is a well-known kind of herb that has been used in traditional medicine for thousands of years. The extrusion of raw materials from it could improve flavor and enhance bioavailability in food and drug development. The purpose of this study is to investigate antitumor and immune boosting effects of extruded GE in human colon carcinoma cells, splenocytes, and mice-bearing CT26 colon carcinoma cell. Treatment with 100[Formula: see text][Formula: see text]g/mL of extruded GE decreased cell viability and induced the expression of Caspase-3 and Bax in HT29 cells ([Formula: see text]). When we performed DAPI staining, apoptotic bodies with condensed chromatin and fragmented nuclei, known as indicative of apoptotic morphology, increased 24[Formula: see text]h after treatment with 100[Formula: see text][Formula: see text]g/mL of extruded GE. Treatments with extruded GE significantly promoted splenocyte proliferation and IL-2 or IFN-[Formula: see text] secretion, compared with that of control cells ([Formula: see text]). The administration of extruded GE of 200 mg/kg/day decreased tumor growth and Ki-67 or [Formula: see text]-catenin expression in mice ([Formula: see text]). Additionally, we investigated the contents of compounds in extruded GE extracts using ultra performance liquid chromatography. The contents of p-hydroxylbenzyl alcohol and p-hydroxybenzaldehyde in extruded GE were 2.97[Formula: see text]mg/g and 0.04[Formula: see text]mg/g, respectively. It was supposed that antitumor and immunomodulatory effects of extruded GE might exert by the p-hydroxylbenzyl alcohol and p-hydroxybenzaldehyde of many compositions analyzed from extruded GE. These results suggest that extruded GE have the potential to be developed into a natural pharmaceutical and functional food as a cancer chemopreventive agent.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Gastrodia , Fatores Imunológicos , Extratos Vegetais/farmacologia , Baço/imunologia , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/uso terapêutico , Baço/citologia , beta Catenina/genética , beta Catenina/metabolismoRESUMO
BACKGROUND: Bruton's tyrosine kinase (Btk) is critical for activation of B cells and myeloid cells. This study aimed to characterize the effects of HM71224, a novel Btk inhibitor, both in vitro and in a mouse model of experimental arthritis. METHODS: The kinase inhibition profile of HM71224 was analyzed. The in vitro effects of HM71224 on B cells and monocytes were analyzed by examining phosphorylation of Btk and its downstream signaling molecules, along with cytokine production and osteoclast formation. The in vivo effects of HM71224 were investigated in a mouse model of collagen-induced arthritis (CIA). RESULTS: HM71224 irreversibly bound to and inhibited Btk (IC50 = 1.95 nM). The compound also inhibited the phosphorylation of Btk and its downstream molecules such as PLCγ2, in activated Ramos B lymphoma cells and primary human B cells in a dose-dependent manner. Furthermore, HM71224 effectively inhibited the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß by human monocytes, and osteoclast formation by human monocytes. Finally, HM71224 improved experimental arthritis and prevented joint destruction in a murine model of CIA. CONCLUSIONS: HM71224 inhibits Btk in B cells and monocytes and ameliorates experimental arthritis in a mouse model. Thus, HM71224 is a potential novel therapeutic agent for rheumatoid arthritis in humans.