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1.
Chem Biol Interact ; 311: 108755, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31319077

RESUMO

Effective control of white adipose tissue accumulation would provide a therapeutic strategy for obesity, which poses a growing global problem. The plant chemical mangiferin stimulates adenosine monophosphate-activated protein kinase (AMPK), which inhibits adipogenesis and has therefore been considered a therapeutic target for obesity and related diseases. We previously reported the anti-inflammatory properties of 6'-O-acetyl mangiferin (OAM). In this study, we evaluated the potential of OAM as an AMPK activator in vitro in 3T3-L1 preadipocytes. OAM inhibited adipogenesis as indicated by lower intracellular lipid and triglyceride accumulation as well as reduced adipogenic gene and protein expression upon treatment. OAM-treated 3T3-L1 cells excreted more glycerol, indicating increased lipolysis, which was supported by increased expression of lipolysis-related genes, including adipose triglyceride lipase and hormone-sensitive lipase. We determined that OAM upregulates lipolysis via phosphorylation-dependent activation of AMPK. Further, OAM upregulated the ß-oxidation pathway as indicated by enhanced expression of phosphorylated acetyl-CoA-carboxylase and long-chain acyl-CoA synthetase 1. In conclusion, OAM markedly decreased intracellular lipid accumulation by enhancing lipolysis via AMPK activation and by upregulating ß-oxidation. Thus, OAM has potential as a drug for the prevention and/or improvement of obesity and related diseases and deserves further study.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipogenia/efeitos dos fármacos , Gênero Iris/química , Lipólise/efeitos dos fármacos , Xantonas/farmacologia , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Gênero Iris/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , PPAR gama/genética , PPAR gama/metabolismo , Fosforilação/efeitos dos fármacos , Triglicerídeos/metabolismo
2.
Chem Biodivers ; 16(7): e1900033, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30977279

RESUMO

Achillea alpina is widely distributed in Korea and is often used as a folk medicine for stomach disorders. Although a previous study isolated antioxidant compounds (flavonoid O-glucoside, sesquiterpene) from this plant, no systematic study of its chemical constituents had been reported. The present study aimed to identify the phytochemicals present in a methanol extract of A. alpina, assess their potential antioxidant activities in vitro, and determine their effects on melanogenesis in B16F10 melanoma cells. Column chromatographic separation of aqueous fractions of A. alpina led to the isolation of 17 compounds. The chemical structures of these compounds were determined using spectroscopic data from electrospray ionization-mass spectrometry and nuclear magnetic resonance. To the best of our knowledge, the present study is the first to identify compounds 2-10 and 12-17 in A. alpina. Furthermore, compound 6 possessed powerful antioxidant activity, while compound 15 suppressed intracellular tyrosinase activity and thus reduced melanogenesis in B16F10 cells. Therefore, our research suggested that these naturally occurring compounds have the potential to reduce oxidative stress and promote skin whitening. Further investigations will be required to elucidate the mechanisms underlying the antioxidant and antityrosinase activities of these compounds.


Assuntos
Achillea/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Picratos/antagonistas & inibidores , Componentes Aéreos da Planta/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade
3.
Toxicol Res ; 35(2): 191-200, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31015901

RESUMO

Alismatis rhizoma (AR), the dried rhizome of Alisma orientale (Sam.) Juzep, is a well-known, traditional medicine that is used for the various biological activities including as a diuretic, to lower cholesterol and as an anti-inflammatory agent. The present study was carried out to investigate the potential toxicity of the Alismatis rhizoma aqueous extract (ARAE) following 90-day repeated oral administration to Sprague-Dawley rats. ARAE was administered orally to male and female rats for 90 days at 0 (control), 500, 1,000 and 2,000 mg/kg/day (n = 10 for male and female rats for each dose). Additional recovery groups from the control group and high dose group were observed for a 28-day recovery period. Chromatograms of ARAE detected main compounds with four peaks. Treatment-related effects including an increase in the red blood cells, hemoglobin, hematocrit, albumin, total protein, and urine volume were observed in males of the 2,000 mg/kg/day group (p < 0.05). However, the diuretic effect of ARAE was considered, a major cause of hematological and serum biochemical changes. The oral no-observed-adverse-effect level (NOAEL) of the ARAE was > 2,000 mg/kg/day in both genders, and no target organs were identified.

4.
Toxicol Res ; 34(2): 133-141, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29686775

RESUMO

Anti-cancer drugs such as cisplatin and doxorubicin are effectively used more than radiotherapy. Cisplatin is a chemotherapeutic drug, used for treatment of various forms of cancer. However, it has side effects such as ototoxicity and nephrotoxicity. Cisplatin-induced nephrotoxicity increases tubular damage and renal dysfunction. Consequently, we investigated the beneficial effect of cynaroside on cisplatin-induced kidney injury using HK-2 cell (human proximal tubule cell line) and an animal model. Results indicated that 10 µM cynaroside diminished cisplatin-induced apoptosis, mitochondrial dysfunction and caspase-3 activation, cisplatin-induced upregulation of caspase-3/MST-1 pathway decreased by treatment of cynaroside in HK-2 cells. To confirm the effect of cynaroside on cisplatin-induced kidney injury in vivo, we used cisplatin exposure animal model (20 mg/kg, balb/c mice, i.p., once a day for 3 days). Renal dysfunction, tubular damage and neutrophilia induced by cisplatin injection were decreased by cynaroside (10 mg/kg, i.p., once a day for 3 days). Results indicated that cynaroside decreased cisplatin-induced kidney injury in vitro and in vivo, and it could be used for improving cisplatin-induced side effects. However, further experiments are required regarding toxicity by high dose cynaroside and caspase-3/MST-1-linked signal transduction in the animal model.

5.
Biomed Pharmacother ; 93: 165-171, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28628832

RESUMO

This study investigated the effects young leaves of reed (Phragmites communis) water extract (YLR) on melanogenesis and oxidative stress using B16F10 cells. YLR decreased the intracellular melanin content, protein expression and enzyme activity of tyrosinase in a dose-dependent manner. YLR significantly decreased the gene and protein expression of melanogeneis-related proteins, such as microphthalmia-associated transcription factor (MITF), and tyrosinase-related protein-1 and -2. In addition, YLR up-regulated the melanogenesis inhibitory proteins, extracellular signal-regulated kinase (ERK) and protein kinase B (AKT), while it dose-dependently down-regulated p38 and cAMP response element-binding protein (CREB). Moreover, YLR significantly reduced H2O2-induced reactive oxygen species levels in B16F10 cells and showed antioxidant activity based on DPPH and ABTS free radical scavenging activity and SOD-like activity. These results suggest that YLR have anti-melanogensis properties that function through regulation of the CREB/MITF/tyrosinase pathway in B16F10 cells and antioxidant activity. Overall, these findings indicate that YLR has the potential for use in treatment of skin disorders and skin-whitening.


Assuntos
Melanoma Experimental/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Poaceae/química , Animais , Antioxidantes/metabolismo , Linhagem Celular Tumoral , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Melaninas/metabolismo , Melanoma Experimental/metabolismo , Camundongos , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Oxirredutases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
6.
Food Sci Biotechnol ; 26(4): 1045-1053, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-30263635

RESUMO

Oxidative damage leads to many diseases. In this study, we evaluated the antioxidant effects of 70% ethanol extract of Geranium nepalense (GNE) on hydrogen peroxide-induced cytotoxicity in cell lines: H9c2, SH-SY5Y, HEK293, and BEAS-2B. We determined the free radical scavenging activity of GNE using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and superoxide dismutase-like activities, as well as the polyphenol and flavonoid contents of GNE. The results showed that GNE scavenged DPPH and ABTS radicals in a dose-dependent manner. In addition, it contained abundant contents of total polyphenol and flavonoid contents and strongly suppressed cellular reactive oxygen species, thereby protecting H2O2-induced cytotoxicity in H9c2, SH-SY5Y, HEK293, and BEAS-2B cell lines. The powerful antioxidant activity exhibited by GNE, both in vitro and in cell systems, was attributed to its free radical scavenging activity. Therefore, GNE may be useful in preventing oxidative stress-induced diseases including Alzheimer's disease, respiratory inflammatory disease, and chronic kidney diseases.

7.
Lab Anim Res ; 32(3): 144-150, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27729930

RESUMO

Dendrobium moniliforme (L.) Sw., an herb of the Orchidaceae family, has long been used in traditional medicine to strengthen bones, nourish the stomach, and promote the production of bodily fluid. Recently, polysaccharides isolated from Dendrobium have been used in functional foods and nutraceutical products. A traditional method to process Dendrobium is to soak fresh stems in an ethanol solution, which is the most important factor to ensure high yields of aqueous-extractable polysaccharides. The present study was carried out to investigate the potential acute toxicity of D. moniliforme aqueous extract (DMAE), by a single oral dose in Sprague-Dawley rats. The test article was orally administered once by gavage to male and female rats at doses of 0, 2,500, and 5,000 mg/kg body weight (n=5 male and female rats for each dose). Throughout the study period, no treatment-related deaths were observed and no adverse effects were noted in clinical signs, body weight, food consumption, serum biochemistry, organ weight, or gross findings at any dose tested. The results show that a single oral administration of DMAE did not induce any toxic effects at a dose below 5,000 mg/kg in rats, and the minimal lethal dose was considered to be over 5,000 mg/kg body weight for both sexes. With respect to cytotoxicity, the cell viability of human embryonic kidney (HEK293) cells was less than 50% when the cells were treated with 10 mg/mL aqueous extract for 24 h.

8.
Chem Biol Interact ; 257: 54-60, 2016 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-27474068

RESUMO

A series of acylated xanthone C-glucosides were identified from the methanolic extract of whole Iris rossii Baker. The major constituent was characterized as 6'-O-acetyl mangiferin (OAM), and complete structure elucidation was carried out using 2D NMR (COSY, HSQC, and HMBC) and LC-IT-TOF-MS analyses. The present study is the first to report the anti-inflammatory effects of 6'-O-acetyl mangiferin from Iris rossii Baker on the lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 macrophage cells. OAM strongly suppressed protein expression of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2), thereby inhibiting the production of nitric oxide (NO), prostaglandin E2 (PGE2), and cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). Furthermore, OAM inhibited the LPS-induced phosphorylation of ERK, JNK, and p38, which led to the blockade of nuclear factor-kappa B (NF-κB) and inhibitor kappa B (IκB)-α activation. These results suggest that the anti-inflammatory effects of OAM may be attributed to the downregulation of COX-2 and iNOS via the suppression of NF-κB and the MAPK signaling pathway in RAW264.7 macrophages.


Assuntos
Anti-Inflamatórios/farmacologia , Gênero Iris/química , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Xantonas/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Células RAW 264.7 , Xantonas/química , Xantonas/isolamento & purificação
9.
Food Funct ; 7(2): 689-97, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26838182

RESUMO

This study examined the effects of syringic acid (SA) on obese diet-induced hepatic dysfunction. Mice were fed high-fat diet (HFD) with or without SA (0.05%, wt/wt) for 16 weeks. SA reduced the body weight, visceral fat mass, serum levels of leptin, TNFα, IFNγ, IL-6 and MCP-1, insulin resistance, hepatic lipid content, droplets and early fibrosis, whereas it elevated the circulation of adiponectin. SA down-regulated lipogenic genes (Cidea, Pparγ, Srebp-1c, Srebp-2, Hmgcr, Fasn) and inflammatory genes (Tlr4, Myd88, NF-κB, Tnfα, Il6), whereas it up-regulated fatty acid oxidation genes (Pparα, Acsl, Cpt1, Cpt2) in the liver. SA also decreased hepatic lipogenic enzyme activities and elevated fatty acid oxidation enzyme activities relative to the HFD group. These findings suggested that dietary SA possesses anti-obesity, anti-inflammatory and anti-steatotic effects via the regulation of lipid metabolic and inflammatory genes. SA is likely to be a new natural therapeutic agent for obesity or non-alcoholic liver disease.


Assuntos
Anti-Inflamatórios/administração & dosagem , Fígado Gorduroso/tratamento farmacológico , Ácido Gálico/análogos & derivados , Obesidade/tratamento farmacológico , Animais , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Ácido Gálico/administração & dosagem , Humanos , Insulina/genética , Insulina/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Leptina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Obesidade/genética , Obesidade/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/metabolismo
10.
Nutr Res Pract ; 9(4): 364-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26244074

RESUMO

BACKGROUND/OBJECTIVES: Inflammation is associated with various types of acute and chronic alcohol liver diseases. In this study, we examined whether umbelliferone (7-hydroxycoumarin, UF) ameliorates chronic alcohol-induced liver damage by modulating inflammatory response and the antioxidant system. METHODS: Rats were fed a Liber-Decarli liquid diet containing 5% alcohol with or without UF (0.05 g/L) for 8 weeks, while normal rats received an isocaloric carbohydrate liquid diet. RESULTS: Chronic alcohol intake significantly increased serum tumor necrosis factor-α (TNF-α) and interleukin 6 levels and decreased interleukin 10 level; however, UF supplementation reversed the cytokines related to liver damage. UF significantly suppressed hepatic lipopolysaccharide binding protein, toll-like receptor 4 (TLR4), nuclear factor kappa B, and TNF-α gene expression increases in response to chronic alcohol intake. Masson's trichrome staining revealed that UF improved mild hepatic fibrosis caused by alcohol, and UF also significantly increased the mRNA expressions and activities of superoxide dismutase and catalase in liver, and thus, decreased lipid peroxide and mitochondrial hydrogen peroxide levels. CONCLUSIONS: The findings of this study indicate that UF protects against alcohol-induced liver damage by inhibiting the TLR4 signaling pathway and activating the antioxidant system.

11.
Alcohol ; 48(7): 707-15, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25262573

RESUMO

This study investigated the effects of umbelliferone (UF) on alcoholic fatty liver and its underlying mechanism. Rats were fed a Lieber-DeCarli liquid diet with 36% of calories as alcohol with or without UF (0.05 g/L) for 8 weeks. Pair-fed rats received an isocaloric carbohydrate liquid diet. UF significantly reduced the severity of alcohol-induced body weight loss, hepatic lipid accumulation and droplet formation, and dyslipidemia. UF decreased plasma AST, ALT, and γGTP activity. UF significantly reduced hepatic cytochrome P450 2E1 activities and increased alcohol dehydrogenase and aldehyde dehydrogenase 2 activities compared to the alcohol control group, which resulted in a lower plasma acetaldehyde level in the rats that received UF. Chronic alcohol exposure inhibited hepatic AMPK activation compared to the pair-fed rats, which was reversed by UF supplementation. UF also significantly suppressed the lipogenic gene expression (SREBP-1c, SREBP-2, FAS, CIDEA, and PPARγ) and elevated the fatty acid oxidation gene expression (PPARα, Acsl1, CPT, Acox, and Acaa1a) compared to the alcohol control group, which could lead to inhibition of FAS activity and stimulation of CPT and fatty acid ß-oxidation activities in the liver of chronic alcohol-fed rats. These results indicated that UF attenuated alcoholic steatosis through down-regulation of SREBP-1c-mediated lipogenesis and up-regulation of PPARα-mediated fatty acid oxidation. Therefore, UF may provide a promising natural therapeutic strategy against alcoholic fatty liver.


Assuntos
Fígado Gorduroso Alcoólico/tratamento farmacológico , PPAR alfa/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/efeitos dos fármacos , Umbeliferonas/uso terapêutico , Álcool Desidrogenase/metabolismo , Aldeído Desidrogenase/metabolismo , Aldeído-Desidrogenase Mitocondrial , Animais , Citocromo P-450 CYP2E1/metabolismo , Suplementos Nutricionais , Hipolipemiantes/uso terapêutico , Ifosfamida/análogos & derivados , Ifosfamida/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Proteínas Mitocondriais/metabolismo , PPAR alfa/fisiologia , Ratos , Ratos Sprague-Dawley , Proteína de Ligação a Elemento Regulador de Esterol 1/fisiologia
12.
Chem Biol Interact ; 216: 9-16, 2014 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-24661945

RESUMO

This study was conducted to evaluate the effects of umbelliferone (UF) and 4-methylumbelliferone (mUF) on high-fat diet-induced hypertriglyceridemia and hyperglycemia in mice. The mice were assigned to normal control, high-fat control, and high-fat with UF or mUF groups. For UF or mUF groups, the high-fat diet was supplemented with UF or mUF at 0.02% (wt/wt) for 12weeks. Both UF and mUF significantly decreased plasma triglyceride, free fatty acid and glucose levels, adipocyte size, white adipose tissue weights, and hepatic phosphatidate phosphohydrolase activity and significantly increased plasma adiponectin levels and hepatic fatty acid ß-oxidation activity compared with the high-fat control group. UF and mUF improved glucose intolerance and hepatic steatosis in the high-fat fed mice. Long-term high-fat diet intake induced an increase in hepatic CYP2E1 activity and lipid peroxide and cytosolic hydrogen peroxide contents and suppressed superoxide dismutase and glutathione peroxidase activities, which were reversed by UF and mUF supplementation. These results indicate that UF and mUF similarly ameliorate hypertriglyceridemia and hyperglycemia partly by modulating hepatic lipid metabolism and the antioxidant defense system along with increasing adiponectin levels.


Assuntos
Gorduras na Dieta/efeitos adversos , Himecromona/administração & dosagem , Hiperglicemia/induzido quimicamente , Hipertrigliceridemia/induzido quimicamente , Umbeliferonas/administração & dosagem , Animais , Glicemia , Peso Corporal , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Gorduras na Dieta/administração & dosagem , Suplementos Nutricionais , Ingestão de Energia , Regulação da Expressão Gênica , Hiperglicemia/tratamento farmacológico , Hipertrigliceridemia/tratamento farmacológico , Peroxidação de Lipídeos , Lipídeos/sangue , Lipídeos/química , Fígado/química , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
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