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1.
Food Sci Nutr ; 8(7): 3738-3749, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32724636

RESUMO

Artemisia annua L. is an annual herb belonging to the Asteraceae family. It is commonly grown in parts of Asia, including Korea and China, and is called by its nickname Gae-ddong-ssuk, or Chung-ho. The herb is well known for its positive effects on fever and hemostasis, as well as its antibiotic effects. To evaluate the protective properties of A. annua L. on the liver, an acute liver failure animal model was set up with intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-galN) in C57BL/6J mice, showing increased levels of AST (aspartate transaminase) and ALT (alanine transaminase). Oral administration of the extract of A. annua L. (EAA) for 2 weeks reduced the level of AST and ALT up to 50% of the levels in the negative control group treated with water vehicle. The efficacy of EAA was more effective than that in a comparative positive control group treated with milk thistle extract. Moreover, EAA protected hepatic cells and tissues from oxidative stresses and inflammatory damages, showing downregulation of inflammatory cytokines such as interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). We also found that LPS stimulated the mouse macrophage cell line, Raw264.7, and secreted a tremendous level of proinflammatory cytokines and the secretion of these cytokines was reduced with EAA treatment via downregulation of mitogen-activated protein kinase phosphorylation and p65 translocation. This study demonstrated that A. annua L. extract is a promising treatment for protection against and recovery from liver damage, as well as maintenance of liver health.

2.
J Food Biochem ; 44(8): e13232, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32497278

RESUMO

We investigated the effect of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (LD) on ethanol (EtOH)-mediated liver injury and explored the underlying mechanisms. Administration of LD synergistically reduced relative liver weight and decreased the levels of serum biomarkers of hepatic injury. Histopathological and biochemical analyses indicated that LD synergistically attenuated hepatic accumulation of triacylglycerides (TGs) and restored the levels of mRNAs related to fatty acid metabolism. In addition, LD significantly reduced EtOH-induced hepatic oxidative stress by attenuating the reduction in levels of nuclear factor E2-related factor 2 (Nrf2) mRNA and enhancing antioxidant activity. Moreover, LD decreased the EtOH-mediated increase in levels of hepatic tumor necrosis factor-α (TNF-α) mRNA. In vitro, LD significantly scavenged free radicals, increased cell viability against tert-butylhydroperoxide (tBHP), and transactivated Nrf2 target genes in HepG2 cells. Furthermore, LD decreased levels of pro-inflammatory mediators in lipopolysaccharide-stimulated Raw264.7 cells. Therefore, LD shows promise for preventing EtOH-mediated liver injury. PRACTICAL APPLICATIONS: There were no approved therapeutic agents for preventing and/or treating alcoholic liver diseases. In this study, a 2:1 (w/w) mixture of lemon balm and dandelion leaf extract (DL) synergistically ameliorated EtOH-induced hepatic injury by inhibiting lipid accumulation, oxidative stress, and inflammation. Our findings will enable the development of a novel food supplement for the prevention or treatment of alcohol-mediated liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Melissa , Taraxacum , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Etanol/toxicidade , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
3.
Food Sci Biotechnol ; 28(1): 243-251, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30815316

RESUMO

In this study, we examined the effects of the water extract of Neolentinus lepideus (WENL), an edible mushroom, on ethanol-induced hepatic lipid accumulation. Ethanol-induced oil red O-positive spots on AML-12 hepatocytes were attenuated by WENL treatment. Furthermore, the oral administration of WENL in acute and chronic ethanol-fed mouse models resulted in the decrease in blood triglyceride and the accumulation of lipid droplets in the liver. Interestingly, the transcriptional expression related to lipid metabolisms, such as sterol regulatory element-binding protein 1, and cytochrome P450 2E1, was decreased by WENL treatment in both ethanol-induced AML-12 hepatocytes and our chronic ethanol-fed mouse models. In addition, WENL effectively attenuated the ethanol induced activation of MAP kinases and NF-κB in AML-12 hepatocytes. Taken together, our results suggested that WENL can be effective in alleviating alcohol-induced hepatic lipid accumulation and may be used as potential candidate for the prevention of alcoholic fatty liver disease.

4.
Molecules ; 23(11)2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30360474

RESUMO

Cornus walteri Wanger (Cornaceae) has been broadly used in traditional East Asian medicine for the treatment of various disorders, including skin inflammation and diarrhea. As part of our efforts to identify structurally and/or biologically new compounds from Korean medicinal plants, we have explored potentially new bioactive constituents from C. walteri. In the present study, seven triterpenoids (1⁻7) were isolated from C. walteri stems and stem bark. Compounds 1⁻3 were new tirucallane triterpenoids (cornusalterins N-P) and compounds 4⁻7 were isolated for the first time from C. walteri. The structures of the new compounds were determined based on 1D and 2D NMR spectroscopic data interpretations and HR-ESIMS, as well as a computational method coupled with a statistical procedure (DP4+). The regulatory effects of the isolated triterpenoids (1⁻7) on mesenchymal stem cell (MSC) differentiation to adipocytes and osteoblasts were examined in the C3H10T1/2 cell line. Although these compounds had little effect on MSC differentiation to osteoblasts, lipid droplet formation in adipocyte-differentiated MSCs decreased in the presence of the seven triterpenoids. Compounds 1 and 4 each had a relatively distinct correlation between dose and efficacy, showing adipogenesis suppression at higher concentrations. Our findings demonstrate that the active compounds 1 and 4 can exert beneficial effects in regulation of adipocyte differentiation.


Assuntos
Adipócitos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Cornus/química , Osteoblastos/efeitos dos fármacos , Casca de Planta/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Triterpenos/farmacologia , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Linhagem Celular , Espectroscopia de Ressonância Magnética , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Estrutura Molecular , Osteoblastos/citologia , Osteoblastos/metabolismo , Compostos Fitoquímicos/química , Extratos Vegetais/química , Relação Estrutura-Atividade , Triterpenos/química
5.
Cell Death Dis ; 9(9): 876, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30158592

RESUMO

Stimulation of white adipose tissue (WAT) browning is considered as a potential approach to treat obesity and metabolic diseases. Our previous studies have shown that phytochemical butein can stimulate WAT browning through induction of Prdm4 in adipocytes. Here, we investigated the effects of butein on diet-induced obesity and its underlying molecular mechanism. Treatment with butein prevented weight gains and improved metabolic profiles in diet-induced obese mice. Butein treatment groups also displayed higher body temperature, increased energy expenditure, and enhanced expression of thermogenic genes in adipose tissue. Butein also suppressed body weight gains and improved glucose and insulin tolerance in mice housed at thermoneutrality (30 °C). These effects were associated with adipose-selective induction of Prdm4, suggesting the role of Prdm4 in butein-mediated anti-obese effects. To directly assess the in vivo role of Prdm4, we generated aP2-Prdm4 transgenic mouse lines overexpressing Prdm4 in adipose tissues. Adipose-specific transgenic expression of Prdm4 recapitulated the butein's actions in stimulating energy expenditure, cold tolerance, and thermogenic gene expression, resulting in prevention of obesity and improvement of metabolism. Mechanistically, direct inhibition of PI3Kα activity followed by selective suppression of its downstream Akt1 mirrored butein's effect on Ucp1 expression and oxygen consumption. In addition, effects of butein were completely abolished in Akt1 KO mouse embryonic fibroblasts. Together, these studies demonstrate the role of butein in obesity and metabolic diseases, further highlighting that adipose PI3Kα-Akt1-Prdm4 axis is a regulator of energy expenditure.


Assuntos
Tecido Adiposo/metabolismo , Proteínas de Ligação a DNA/metabolismo , Metabolismo Energético/fisiologia , Resistência à Insulina/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição/metabolismo , Aumento de Peso/fisiologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/fisiologia , Tecido Adiposo/efeitos dos fármacos , Animais , Linhagem Celular , Chalconas/farmacologia , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/efeitos dos fármacos , Camundongos , Camundongos Knockout , Camundongos Obesos , Obesidade/metabolismo , Termogênese/efeitos dos fármacos , Termogênese/fisiologia , Proteína Desacopladora 1/metabolismo , Aumento de Peso/efeitos dos fármacos
6.
J Agric Food Chem ; 66(11): 2677-2684, 2018 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-29444566

RESUMO

Oryza sativa L. is consumed globally as a staple food, and its roots have been used as a Korean and Chinese medical supplement for protection of the stomach and lungs and for amelioration of vomiting and fever. In our continuing search for biologically effective metabolites from Korean natural materials, we found that an EtOH extract of O. sativa root reciprocally regulated adipocyte and osteoblast differentiation. Chemical analysis of the EtOH extract using a bioassay-guided fractionation protocol led to the isolation and determination of two novel lignans, oryzativols A and B, responsible for these regulatory activities. Using 1D and 2D nuclear magnetic resonance spectroscopic analyses, high-resolution mass spectrometry, and circular dichroism analysis, the structures of the novel compounds were elucidated. We examined their effects on the regulation of mesenchymal stem cell differentiation. Treatment with oryzativol A in the human mesenchymal cell line C3H10T1/2 suppressed gene expression of peroxisome proliferator activated receptor γ, which resulted in a reduction in adipogenesis. Oryzativol A also enhanced the expression of Runx2 and cellular differentiation into osteoblasts in the same mesenchymal stem cell line.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Produtos Biológicos/farmacologia , Oryza/química , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Linhagem Celular , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteoblastos/citologia , Osteoblastos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química
7.
J Photochem Photobiol B ; 161: 211-6, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27262853

RESUMO

Nelumbo nucifera has long been used in traditional medicine in East Asian countries such as China and Korea. In this study, we report the different property of several Nelumbo nucifera leaf (NNL) extracts on adipocyte differentiation. Adipogenesis was stimulated by administration of dichloromethyl (DCM) or n-hexan extract of NNL but attenuated by that of water extract. We also show that topical administration of DCM extract of NNL attenuated ultraviolet-B (UVB)-mediated wrinkle formation and reduction of subcutaneous (SC) fat in vivo. Interestingly, UVB-induced blood contents of triglyceride (TG) were attenuated significantly by topical administration of the DCM extract. In addition, we found that UVB-induced expression of cytokines (interleukin-6; IL-6, interleukin-8; IL-8, and monocyte chemotactic protein-3; MCP3), which were reported as regulators in SC fat metabolism, was attenuated in mouse skin fibroblast cells upon administration of the DCM extract. Collectively, our data suggest that topical administration of DCM extract of NNL, which plays a regulatory role in adipogenesis, could attenuate UVB-induced wrinkle formation and the metabolism of blood lipids by regulating the expression of cytokines such as IL-6, IL-8, and MCP3 in skin fibroblast cells. Our findings support further development of DCM extract of NNL as a potential therapeutic agent for prevention of photoaging-related disorders.


Assuntos
Citocinas/metabolismo , Nelumbo/química , Extratos Vegetais/química , Substâncias Protetoras/química , Envelhecimento da Pele/efeitos da radiação , Gordura Subcutânea/fisiologia , Raios Ultravioleta , Células 3T3-L1 , Adipogenia/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Quimiocina CCL7/genética , Quimiocina CCL7/metabolismo , Citocinas/genética , Ácidos Graxos não Esterificados/sangue , Feminino , Expressão Gênica/efeitos dos fármacos , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Medicina Tradicional do Leste Asiático , Camundongos , Camundongos Pelados , Células NIH 3T3 , Nelumbo/metabolismo , Extratos Vegetais/farmacologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Substâncias Protetoras/farmacologia , Pele/patologia , Envelhecimento da Pele/efeitos dos fármacos , Triglicerídeos/sangue
8.
Int J Mol Sci ; 17(3): 328, 2016 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-26950116

RESUMO

Gleditsia sinensis thorns (GST) have been used as a traditional medicine for carbuncles and skin diseases. The purpose of this study was to decide whether non-toxicological levels of water extract of GST (WEGST) are effective in inhibiting the progress of prostate cancer formation and to identify the target molecule involved in the WEGST-mediated inhibitory process of prostate cancer cell migration and in vivo tumor formation. Through the Boyden chamber migration assay, we found that non-toxic levels of WEGST could not attenuate the PC3 migration to the bottom area coated with serum but significantly inhibited PC3 cell migration to the collagen-coated bottom area. We also found that non-toxic levels of WEGST significantly attenuated collagen against adhesion. Interestingly, ectopic administration of WEGST could not affect the expression of α2ß1 integrin, which is known as a receptor of collagen. However, when the PC3 cells adhered to a collagen-coated plate, the expression of α2 integrin but not that of ß1 integrin was significantly inhibited by the administration of non-toxic levels of WEGST, leading to the inhibition of focal adhesion kinase (FAK) phosphorylation. Furthermore, oral administration of WEGST (25 mg/kg/day) significantly inhibited the size of a PC3 cell-xenografted tumor. Taken together, these results suggest a novel molecular mechanism for WEGST to inhibit prostate cancer progression at particular stages, such as collagen-mediated adhesion and migration, and it might provide further development for the therapeutic use of WEGST in the treatment of prostate cancer progression.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Movimento Celular/efeitos dos fármacos , Gleditsia/química , Integrina alfa2beta1/metabolismo , Extratos Vegetais/uso terapêutico , Próstata/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Colágeno/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Masculino , Camundongos Nus , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Transdução de Sinais/efeitos dos fármacos
9.
Korean J Food Sci Anim Resour ; 35(1): 58-70, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26761801

RESUMO

This study was conducted to examine the effect of egg shell membrane hydrolysates (ESMH) on wrinkle, UV, and moisture protection for cosmetic use. ESMH were fragmented as whole ESMH (before fractioning), Fraction I (> 10 kDa), Fraction II (3-10 kDa), and Fraction III (< 3 kDa). In order to test whether fractionated ESMH can be used for functional cosmetic materials, we examined not only the level of hyaluronic acid and collagen production, but also the MMP-1 activity using a HaCaT and CCD-986Sk cell line. Our study treated each sample of fractionated ESMH with different concentrations (0.01, 0.1, 1 mg/mL). In our in vivo research, we used hairless mice that had been exposed to UV-B to induce wrinkles for 7 wk, then applied Fraction I to the treatment group for 5 wk and then tested skin thickness, minimum erythema dose and moisture content. In addition, Fraction I was high in collagen and HA biosynthesis and it was better than TGF-ß in improving of the skin. When TNF-α caused MMP-1 activity in the CCD-986Sk cells, the whole ESMH and Fraction I proved to be effective in hindering the induction of collagenase depending on the concentration, and also showed outstanding effects in the suppression of skin aging. We found that the treatment group mice's UV-B radiation-induced skin damage was largely mitigated compared to that of the non-treatment group mice. Thus, we have concluded that EMSH helps to mitigate UV-B radiation-induced wrinkles, collagen, HA, MMP-1 activity and can be used for functional cosmetic materials.

10.
Prev Nutr Food Sci ; 19(3): 220-6, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25320720

RESUMO

In the present report, the effects of blanching, steaming, and high temperature/high pressure processing (HTHP) on the amino acid contents of commonly consumed Korean root vegetables, leaf vegetables, and pulses were evaluated using an Automatic Amino Acid Analyzer. The total amino acid content of the samples tested was between 3.38 g/100 g dry weight (DW) and 21.32 g/100 g DW in raw vegetables and between 29.36 g/100 g DW and 30.55 g/100 g DW in raw pulses. With HTHP, we observed significant decreases in the lysine and arginine contents of vegetables and the lysine, arginine, and cysteine contents of pulses. Moreover, the amino acid contents of blanched vegetables and steamed pulses were more similar than the amino acid contents of the HTHP vegetables and HTHP pulses. Interestingly, lysine, arginine, and cysteine were more sensitive to HTHP than the other amino acids. Partial Least Squares-Discriminate Analyses were also performed to discriminate the clusters and patterns of amino acids.

11.
J Med Food ; 17(7): 772-81, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24927400

RESUMO

Pathological increases in adipogenic potential with decreases in osteogenic differentiation occur in osteoporotic bone marrow cells. Previous studies have shown that bioactive materials isolated from natural products can reciprocally regulate adipogenic and osteogenic fates of bone marrow cells. In this study, we showed that Eupatorium japonicum stem extracts (EJE) suppressed lipid accumulation and inhibited the expression of adipocyte markers in multipotent C3H10T1/2 and primary bone marrow cells. Conversely, EJE stimulated alkaline phosphatase activity and induced the expression of osteoblast markers in C3H10T1/2 and primary bone marrow cells. Daily oral administration of 50 mg/kg of EJE for 6 weeks to ovariectomized rats prevented body weight increase and bone mineral density decrease. Finally, activity-guided fractionation led to the identification of coumaric acid and coumaric acid methyl ester as bioactive anti-adipogenic and pro-osteogenic components in EJE. Taken together, our data indicate a promising possibility of E. japonicum as a functional food and as a therapeutic intervention for preventing osteoporosis and bone fractures.


Assuntos
Adipócitos/efeitos dos fármacos , Doenças Ósseas Metabólicas/prevenção & controle , Eupatorium/química , Células-Tronco Mesenquimais/citologia , Osteoblastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Células 3T3 , Adipócitos/citologia , Adipogenia/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/etiologia , Células da Medula Óssea , Diferenciação Celular/efeitos dos fármacos , Ácidos Cumáricos/análise , Ácidos Cumáricos/farmacologia , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Osteoblastos/citologia , Osteoporose/complicações , Extratos Vegetais/farmacologia , Caules de Planta/química , Ratos , Ratos Sprague-Dawley
12.
J Food Sci ; 78(11): E1713-20, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24245888

RESUMO

Plodia interpunctella is a major storage pest that penetrates into food packaging and causes serious economic losses, as well as posing health risks. The goal of this study was to develop effective anti-insect polymer strips against P. interpunctella by using plant essential oil (EO) and polyvinyl alcohol (PVA). The EO of cinnamon (Cinnamomum zeylanicum, CO) bark was used as an insect repellent, and fumigant mortality and the repellent activity of CO were measured to evaluate subsistent anti-insect properties through newly designed traps. Repellent activity was also examined with several foods to simulate the storage environment. The mortality rate with CO after fumigation for 120 h was 63%. In the repellent assay, CO-treated strips, but not control strips, effectively repelled P. interpunctella in both "with foods" and "without foods" groups. A PVA-CO strip sachet (PCO sachet) was developed to control the volatility of CO, and the PCO sachet demonstrated robust repellent activity. The loading contents of CO at the center and edges of strips were 39.41% and 39.59%, respectively, and through the results of FT-IR, it inferred that CO was physically diffused in the PVA polymer matrix, not forming chemical bonds. In a release test using a gas chromatography, the PCO sachet showed remarkable controlled release of CO. These results demonstrate that the anti-insect effects of CO can be maintained throughout the distribution and storage periods of foods using PCO sachets.


Assuntos
Cinnamomum zeylanicum/química , Inseticidas/química , Lepidópteros/efeitos dos fármacos , Óleos Voláteis/química , Polímeros/química , Álcool de Polivinil/química , Animais , Fenômenos Químicos , Cromatografia Gasosa , Embalagem de Alimentos/métodos , Fumigação/métodos , Lepidópteros/crescimento & desenvolvimento , Espectroscopia de Infravermelho com Transformada de Fourier
13.
Nat Commun ; 3: 978, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22864571

RESUMO

Fas-associated protein with death domain (FADD) is a pivotal component of death receptor-mediated extrinsic apoptosis and necroptosis. Here we show that FADD is regulated by Makorin Ring Finger Protein 1 (MKRN1) E3 ligase-mediated ubiquitination and proteasomal degradation. MKRN1 knockdown results in FADD protein stabilization and formation of the rapid death-inducing signalling complex, which causes hypersensitivity to extrinsic apoptosis by facilitating caspase-8 and caspase-3 cleavage in response to death signals. We also show that MKRN1 and FADD are involved in the regulation of necrosome formation and necroptosis upon caspase inhibition. Downregulation of MKRN1 results in severe defects of tumour growth upon tumour necrosis factor-related apoptosis-inducing ligand treatment in a xenograft model using MDA-MB-231 breast cancer cells. Suppression of tumour growth by MKRN1 depletion is relieved by simultaneous FADD knockdown. Our data reveal a novel mechanism by which fas-associated protein with death domain is regulated via an ubiquitination-induced degradation pathway.


Assuntos
Apoptose/fisiologia , Proteína de Domínio de Morte Associada a Fas/metabolismo , Necrose/metabolismo , Receptores de Morte Celular/metabolismo , Ubiquitinação/fisiologia , Animais , Apoptose/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Proteína de Domínio de Morte Associada a Fas/genética , Citometria de Fluxo , Células HeLa , Humanos , Imunoprecipitação , Técnicas In Vitro , Camundongos , Necrose/genética , Receptores de Morte Celular/genética , Análise Serial de Tecidos , Ubiquitinação/genética
14.
J Med Food ; 14(4): 360-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21303259

RESUMO

Previous studies showed that feeding diets containing the mature fruits of Sophora japonica L. prevented body weight gain and reduced fat mass in high-fat diet-induced obese mice. This observation has led to the hypothesis that extracts from S. japonica L. may inhibit adipocyte differentiation of preadipocytes. To elucidate the possible mechanisms for the anti-obesity action of S. japonica L., its effects on adipocyte differentiation were investigated in C3H10T1/2 mesenchymal stem cells and 3T3-L1 preadipocyte cells. The mature fruit of S. japonica L. was partitioned with ethanol, hexane, dichloromethane, ethyl acetate (EtOAc), and butanol to identify the active fractions. The EtOAc fraction extracts inhibited morphological differentiation and lipid accumulation in the C3H10T1/2 and 3T3-L1 preadipocytes. Molecular studies indicated that the EtOAc fraction extracts also reduced the expression of peroxisome proliferator-activated receptor γ and other adipocyte markers. Furthermore, among the fractions, the EtOAc fraction extracts had the highest total phenolic contents, suggesting that the polyphenols in the EtOAc fractions mediated the anti-adipogenic effects. Finally, high-performance liquid chromatography identified genistein, a known anti-adipogenic compound, as the probable mediator of the anti-adipogenic effects of the EtOAc fractions. This work validates the beneficial roles of S. japonica L. in controlling body weight and obesity-related metabolic diseases.


Assuntos
Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Sophora/química , Células 3T3-L1 , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular , Cromatografia Líquida de Alta Pressão , Flavonoides/farmacologia , Genisteína , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Obesos , Fenóis/farmacologia , Polifenóis
15.
Bioorg Med Chem Lett ; 20(18): 5385-8, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20719504

RESUMO

Subvellerolactones B (1), D (2), and E (3), structurally unusual lactarane sesquiterpenoids, were isolated from the fruiting bodies of Lactarius subvellereus together with four known lactarane sesquiterpenes (4-7). The chemical structures and stereochemistries of compounds 1-3 were determined on the basis of spectroscopic analyses, including 1D and 2D NMR experiments and a convenient Mosher ester procedure. Subvellerolactone B (1) exhibited cytotoxicity against the A549, SK-MEL-2, and HCT-15 cell lines with IC50 values of 26.5, 18.3, and 14.2 microM, respectively, and subvellerolactones D (2) and E (3) showed cytotoxicity against the A549 and HCT-15 cell lines (IC50 (2): 25.1 and 17.8 microM, and IC50 (3): 19.6 and 28.7 microM, respectively).


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Basidiomycota/química , Carpóforos/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citotoxinas/química , Citotoxinas/isolamento & purificação , Citotoxinas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Neoplasias/tratamento farmacológico , Sesquiterpenos/isolamento & purificação
17.
J Lipid Res ; 51(9): 2775-84, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20519739

RESUMO

We previously described the use of a cell-based screening approach to identify small molecules that regulate adipocyte differentiation. Here we identify the amiloride derivative phenamil as an adipogenic compound. Phenamil acutely induces expression of the key transcription factor of adipogenesis, peroxisome proliferator-activated receptor gamma (PPARgamma) and, consequently, promotes the differentiation of multiple preadipocyte cell lines, including 3T3-L1 and F442A. Interestingly, the adipogenic action of phenamil is distinct from and additive with both PPARgamma ligands and the previously identified adipogenic small molecule harmine. To identify signaling pathways mediating phenamil's effects, we performed transcriptional profiling of 3T3-F442A preadipocytes. ETS variant 4 (ETV4) was identified as a gene rapidly induced by phenamil but not by other adipogenic small molecules or PPARgamma agonists. Transient expression of ETV4 in preadipocytes enhances the expression of PPARgamma. Stable overexpression of ETV4 promotes expression of PPARgamma and its downstream target genes and enhances morphological differentiation. Finally, knockdown of PPARgamma expression by shRNA blocks the effects of phenamil on adipocyte differentiation and gene expression, but it does not block phenamil induction of ETV4, which suggests that ETV4 acts upstream of PPARgamma in differentiation processes. These results identify a phenamil as new small molecule tool for the probing of adipocyte differentiation that acts, at least in part, through induction of ETV4 expression.


Assuntos
Adipócitos/efeitos dos fármacos , Adipócitos/fisiologia , Amilorida/análogos & derivados , Diferenciação Celular/efeitos dos fármacos , PPAR gama/metabolismo , Células 3T3 , Adipócitos/citologia , Amilorida/química , Amilorida/farmacologia , Animais , Proteína delta de Ligação ao Facilitador CCAAT/química , Proteína delta de Ligação ao Facilitador CCAAT/farmacologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Harmina/metabolismo , Camundongos , Estrutura Molecular , Inibidores da Monoaminoxidase/metabolismo , Oxazóis/química , Oxazóis/farmacologia , PPAR gama/agonistas , PPAR gama/genética , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , Transdução de Sinais/fisiologia , Bloqueadores dos Canais de Sódio/química , Bloqueadores dos Canais de Sódio/farmacologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Tirosina/análogos & derivados , Tirosina/química , Tirosina/farmacologia
18.
Nutr Res ; 29(11): 819-24, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19932871

RESUMO

Obesity, a worldwide epidemic, is associated with metabolic diseases such as insulin resistance, dyslipidemia, hypertension, and heart disease. Many strategies, including natural alternative antiobesity agents, have been widely used to prevent obesity. Polyphenolic compounds and flavonoids from natural products are shown to inhibit adipogenesis. Because mature fruits of Sophora japonica L. were previously shown to contain antiadipogenic compounds, we hypothesized that diets with mature fruits of S japonica L. would prevent body weight gain in high-fat diet-induced obesity. Four-week-old mice were fed either a control high-fat diet, or high-fat diet containing 1% or 5% of S japonica L. for 4 weeks. The administration of S japonica L. fed in combination with a 30% high-fat diet significantly decreased body weight gain. S japonica L. also reduced serum and hepatic triglyceride, serum total, and high-density lipoprotein cholesterol. Consistent with the effects of lowering glucose level and fat mass, S japonica L. caused a decrease in the number of large adipocytes and a concomitant increase in the number of small adipocytes, which may explain at least in part the antiobesity effects of S japonica L. Together, these data provide evidence for roles of S japonica L. in the control of body weight and obesity-related metabolic diseases.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Fabaceae , Hipoglicemiantes/uso terapêutico , Obesidade/dietoterapia , Fitoterapia , Preparações de Plantas/uso terapêutico , Aumento de Peso/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Análise de Variância , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , HDL-Colesterol/sangue , Gorduras na Dieta/administração & dosagem , Frutas , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Preparações de Plantas/farmacologia , Triglicerídeos/metabolismo
19.
Arch Pharm Res ; 31(5): 579-86, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18481012

RESUMO

As part of our systematic study of Korean toxic mushrooms, we have investigated the constituents of Amanita subjunquillea. The column chromatographic separation of the MeOH extract of A. subjunquillea led to the isolation of four ergosterols, two cerebrosides and four cyclopeptides. Their structures were determined by spectroscopic methods to be (22E,24R)-5alpha,8alpha-epidioxyergosta-6,9,22-triene-3beta-ol (1), (22E,24R)-5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol (2), (22E,24R)-5alpha,6alpha-epoxyergosta-8,22-diene-3beta,7beta-diol (3), (24S)-ergost-7-en-3beta-ol (4), 8,9-dihydrosoyacerebroside I (5), soyacerebroside I (6), beta-amanitin (7), phalloin (8), alpha-amanitin (9), and phalloidin (10). The compounds 1-6 and 8 were isolated for the first time from this mushroom. The isolated compounds were evaluated for the cytotoxicity against A549, SK-OV-3, SK-MEL-2 and HCT15 cells. Compound 9 exhibited significant cytotoxic activity against A549, SK-OV-3, SK-MEL-2 and HCT15 with ED(50) values of 1.47, 0.26, 1.57 and 1.32 microM, respectively.


Assuntos
Amanita/química , Amanitinas/isolamento & purificação , Antineoplásicos/isolamento & purificação , Cerebrosídeos/isolamento & purificação , Ergosterol/análogos & derivados , Ergosterol/isolamento & purificação , Alfa-Amanitina/química , Alfa-Amanitina/isolamento & purificação , Alfa-Amanitina/farmacologia , Amanitinas/química , Amanitinas/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cerebrosídeos/química , Cerebrosídeos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Ergosterol/química , Ergosterol/farmacologia , Humanos , Estereoisomerismo , Relação Estrutura-Atividade
20.
Asia Pac J Clin Nutr ; 16(1): 30-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17215178

RESUMO

To confirm the cytotoxic effect of instant curry containing combined spices on cancer cells in vivo, cancer was induced by transplanting cancer cells to mice, and the development of cancer upon feeding pure curry were examined. The concentration of lipid peroxide in the groups transplanted with cancer cells which were fed with normal feed was 19.6 nM, and it was increased as the amount of pure curry was increased. The concentration of cytochrome P-450 was decreased in the group transplanted with cancer cells which were fed with pure curry and the group without the transplant which were fed with pure curry when compared with the groups which were fed with normal feed. The activity of cytochrome P-450 was decreased as the concentration of cytochrome P-450 was decreased in the groups transplanted with cancer cells. However, it was increased in the groups without cancer cell transplant when over 2% of pure curry was fed. The amount of glutathione was increased in the groups transplanted with cancer cells when over 2% of pure curry was fed. The activities of glutathione peroxidase and glutathione S-transferase were decreased in the groups transplanted with cancer cells which were fed with over 1% of pure curry, and were restored to the level of the group without cancer cell transplant which were fed with normal feed. The superoxide dismutase activity in the groups transplanted with cancer cells was restored to the level of the group without cancer cell transplant which was fed with normal feed when over 1% of pure curry was fed.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Curcumina/química , Fígado/enzimologia , Neoplasias Experimentais/tratamento farmacológico , Animais , Bioensaio , Sistema Enzimático do Citocromo P-450/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos , Glutationa Peroxidase/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Neoplasias Experimentais/enzimologia , Superóxido Dismutase/metabolismo , Células Tumorais Cultivadas/transplante
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