RESUMO
Visceral adipose tissue (VAT) dysfunction has been recently recognized as a potential contributor to the development of Alzheimer's disease (AD). This study aimed to explore the relationship between VAT metabolism and cerebral glucose metabolism in patients with cognitive impairment. This cross-sectional prospective study included 54 patients who underwent 18F-fluorodeoxyglucose (18F-FDG) brain and torso positron emission tomography/computed tomography (PET/CT), and neuropsychological evaluations. VAT metabolism was measured by 18F-FDG torso PET/CT, and cerebral glucose metabolism was measured using 18F-FDG brain PET/CT. A voxel-based analysis revealed that the high-VAT-metabolism group exhibited a significantly lower cerebral glucose metabolism in AD-signature regions such as the parietal and temporal cortices. In the volume-of-interest analysis, multiple linear regression analyses with adjustment for age, sex, and white matter hyperintensity volume revealed that VAT metabolism was negatively associated with cerebral glucose metabolism in AD-signature regions. In addition, higher VAT metabolism was correlated with poorer outcomes on cognitive assessments, including the Korean Boston Naming Test, Rey Complex Figure Test immediate recall, and the Controlled Oral Word Association Test. In conclusion, our study revealed significant relationships among VAT metabolism, cerebral glucose metabolism, and cognitive function. This suggests that VAT dysfunction actively contributes to the neurodegenerative processes characteristic of AD, making VAT dysfunction targeting a novel AD therapy approach.
Assuntos
Encéfalo , Disfunção Cognitiva , Fluordesoxiglucose F18 , Glucose , Gordura Intra-Abdominal , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Masculino , Feminino , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/diagnóstico por imagem , Glucose/metabolismo , Idoso , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Fluordesoxiglucose F18/metabolismo , Estudos Transversais , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Prospectivos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Testes NeuropsicológicosRESUMO
Background: Ginsenoside Rg3, a primary bioactive component of red ginseng, has anti-cancer effects. However, the effects of Rg3-enriched ginseng extract (Rg3RGE) on apoptosis and autophagy in breast cancer have not yet been investigated. In the present study, we explored the anti-tumor effects of Rg3RGE on breast cancer cells stimulated CoCl2, a mimetic of the chronic hypoxic response, and determined the operative mechanisms of action. Methods: The inhibitory mechanisms of Rg3RGE on breast cancer cells, such as apoptosis, autophagy and ROS levels, were detected both in vitro. To determine the anti-cancer effects of Rg3RGE in vivo, the cancer xenograft model was used. Results: Rg3RGE suppressed CoCl2-induced spheroid formation and cell viability in 3D culture of breast cancer cells. Rg3RGE promoted apoptosis by increasing cleaved caspase 3 and cleaved PARP and decreasing Bcl2 under the hypoxia mimetic conditions. Further, we identified that Rg3RGE promoted apoptosis by inhibiting lysosomal degradation of autophagosome contents in CoCl2-induced autophagy. We further identified that Rg3RGE-induced apoptotic cell death and autophagy inhibition was mediated by increased intracellular ROS levels. Similarly, in the in vivo xenograft model, Rg3RGE induced apoptosis and inhibited cell proliferation and autophagy. Conclusion: Rg3RGE-stimulated ROS production promotes apoptosis and inhibits protective autophagy under hypoxic conditions. Autophagosome accumulation is critical to the apoptotic effects of Rg3RGE. The in vivo findings also demonstrate that Rg3RGE inhibits breast cancer cell growth, suggesting that Rg3RGE has potential as potential as a putative breast cancer therapeutic.
RESUMO
This study focused on improving curcumin stability in various pHs and NaCl concentrations and reducing the strong scent of turmeric by the nanoemulsions system and further coating with water-soluble chitosan (WSC). Turmeric extract-loaded nanoemulsions (TE-NEs) were firstly prepared by mixing an oil phase containing turmeric extract, MCT oil, and lecithin, and an aqueous phase containing tween 80 using an ultrasonication method. TE-NEs were further coated with WSC in the ratio of TE-NEs and WSC (1:1 to 1:10). The optimum WSC-TE-NEs exhibited an average particle size of 182 nm, a PDI of 0.317, and a zeta potential of +30.42 mV when WSC-TE-NEs were prepared in the ratio of 1:1. The stability of the WSC-TE-NEs was also assessed by determining the remained curcumin content. The remained curcumin contents of the TE-NEs and the WSC-TE-NEs were higher than that of the turmeric extract (TE) at pH 2~7 and NaCl concentrations of 100~400 mM. Fourier transform infrared (FT-IR) spectra, transmission electron microscope (TEM), and confocal laser scanning microscope (CLSM) images confirmed that the TE-NEs were successfully encapsulated with a WSC coating. As a result of GC analysis, the content of aromatic-turmerone was significantly decreased in the TE-NEs and the WSC-TE-NEs compared to the pristine TE, but there was no significant difference between the TE-NEs and the WSC-TE-NEs. These results suggest that water-soluble chitosan-coated nanoemulsions may be suitable for improving the chemical stability and masking effect of curcumin to facilitate its application in food.
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4-O-Methyl-ascochlorin (MAC), a derivative of the prenyl-phenol antibiotic ascochlorin, promotes accumulation of HIF-1α. In this study, we investigated the molecular mechanisms of the effect of MAC on cell migration and mesenchymal epithelial transition (EMT) processes in breast cancer cells. MAC upregulated cell motility and migration regardless of cell viability, and promoted EMT features by regulating EMT-related proteins and transcription. In addition, the MAC-induced increase in the EMT was closely related to activation of HIF-1α expression. However, the MAC-induced EMT was not associated with AMPK phosphorylation or intracellular ROS, which stimulate HIF-1α expression. Similarly, HIF-1α-mediated autophagy induced by MAC was not related to EMT-related proteins. Inhibition of HIF-1α activity inhibited MAC-stimulated cell migration and increased MAC-induced cell death, indicating that HIF-1α activation is important for MAC-mediated cell migration and survival in breast cancer cells. Together, these results suggest that MAC can be used to investigate the link between HIF-1α activation and other oncogenes or tumor suppressors in breast cancer cells.
Assuntos
Neoplasias da Mama , Transição Epitelial-Mesenquimal , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , TerpenosRESUMO
Zizania latifolia exhibits anti-inflammatory and anti-allergic effects; however, the mechanisms behind these effects are unknown. Here the ethanol extract of Z. latifolia was partitioned using hexane, chloroform, ethyl acetate, butanol, and water. Subsequently, the anti-allergic effects of these fractions were evaluated in vitro. The results showed that the chloroform fraction of Z. latifolia inhibited the release of ß-hexosaminidase and tumor necrosis factor (TNF-α) from RBL-2H3 cells stimulated with dinitrophenyl-bovine serum albumin (DNP-BSA). In addition, this fraction suppressed the expression of cyclooxygenase-2 (COX-2) and inhibited the activation of mitogen-activated protein kinases (MAPKs). The results obtained suggest that the chloroform fraction of Z. latifolia inhibited mast cell-mediated allergic inflammatory responses.
RESUMO
In the present study, we hypothesized that defatted safflower seed which is known to be rich in polyphenols might influence adipogenesis and obesity-related disorders, and therefore the anti-adipogenic and hypolipidemic effects of ethanol extract from defatted safflower (Cathamus tinctorius L.) seeds (CSE) were investigated both in cultured 3T3-L1 preadipocytes and in C57BL/6J ob/ob mice fed a high-fat diet. CSE inhibited adipocyte differentiation of 3T3-L1 preadipocytes and decreased expression of the adipogenic transcription factors, SREBP1c and PPARγ, and their target genes. Six-week-old obese (ob/ob) mice were fed a high-fat diet and treated with CSE (50 or 100 mg/kg/day) by oral gavage for 6 weeks. Body fat mass (epididymal and perirenal white adipose tissues) in the CSE-treated groups was significantly lower than that in the high-fat diet control (HFD) group, whereas average daily food intake was not significantly different among the groups. Plasma and hepatic triglyceride levels and plasma low-density lipoprotein cholesterol level were also significantly lower in the CSE groups compared to the HFD group. These results suggest that CSE which decreases body fat mass and improves lipid profiles in plasma and liver, represents a potential treatment option for obesity and associated metabolic disorders, including hyperlipidemia.
Assuntos
Adipogenia/efeitos dos fármacos , Tecido Adiposo/metabolismo , Carthamus tinctorius , Lipoproteínas LDL/metabolismo , Obesidade/sangue , Extratos Vegetais/farmacologia , Triglicerídeos/metabolismo , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Tecido Adiposo/citologia , Animais , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Composição Corporal/efeitos dos fármacos , Peso Corporal , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Diferenciação Celular , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Obesidade/prevenção & controle , PPAR gama/metabolismo , Extratos Vegetais/uso terapêutico , Sementes/química , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismoRESUMO
Hydroquinone (HQ) is a well-known environmental carcinogen and exposure of humans to HQ can also occur through plant foods, cosmetics, and tobacco products. Although liver is a major organ metabolizing HQ and susceptible to its toxicity, role of HQ in metastatic progression of human hepatocellular carcinoma (HCC) remains unclear. In this study, we examined the effect of HQ on the invasion of HCC cells and its underlying molecular mechanisms. HQ strongly induced matrix metalloproteinase-9 (MMP-9) expression and secretion in HepG2 human hepatoma cells, which were well correlated with increased cell invasion. Mechanistic studies further demonstrated that HQ induced transcriptional activity of MMP-9 gene by activating activator protein-1 (AP-1), the well-known key element mediating MMP-9 gene expression, via MAP kinase (MAPK) signaling pathways. These results suggest that HQ may promote metastatic progression of HCC, although data on in vivo hydroquinone exposure and risk for HCC are contradictory.
Assuntos
Carcinoma Hepatocelular/patologia , Hidroquinonas/farmacologia , Neoplasias Hepáticas/patologia , Metaloproteinase 9 da Matriz/metabolismo , Fator de Transcrição AP-1/metabolismo , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/metabolismo , Indução Enzimática , Células Hep G2 , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/metabolismo , Metaloproteinase 9 da Matriz/biossínteseRESUMO
Methanol extract of Zizania latifolia was partitioned with EtOAc, n-BuOH, and H2O. From the EtOAc layers, a new flavonolignan along with a known flavone and three known flavonolignans, tricin (1), salcolin A (2), salcolin B (3), and salcolin C (4), were isolated through repeated silica gel and ODS column chromatography. The chemical structure of the new flavonolignan was determined to be tricin-4'-O-[erythro-ß-guaiacyl-(7â³-O-methyl)-glyceryl] ether and was named salcolin D (5) based on physicochemical and spectroscopic data, including FT-NMR and ESI-MS. All compounds were isolated for the first time from this plant. Compounds 2-5, tricin derivatives, all exhibited higher anti-inflammatory and anti-allergy activities than tricin. In particular, salcolin D (5) was shown to have the strongest inhibitory activity against LPS-induced NO production in RAW 264.7 cells as well as ß-hexosaminidase release in IgE-sensitized RBL-2H3 cells. These results suggest that the presence of tricin derivatives conveys allergy and inflammation treatment ability to Z. latifolia.
Assuntos
Antialérgicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Flavonoides/química , Poaceae/química , Animais , Antialérgicos/química , Anti-Inflamatórios não Esteroides/química , Linhagem Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Flavonas/química , Flavonas/farmacologia , Flavonoides/farmacologia , Flavonolignanos/química , Flavonolignanos/isolamento & purificação , Flavonolignanos/farmacologia , Imunoglobulina E/farmacologia , Lignanas/química , Lignanas/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , beta-N-Acetil-Hexosaminidases/antagonistas & inibidores , beta-N-Acetil-Hexosaminidases/metabolismoRESUMO
Ganoderma applanatum (GA) and related fungal species have been used for over 2000 years in China to prevent and treat various human diseases. However, there is no critical research evaluating the functionality of GA grown using submerged culture technology. This study aimed to evaluate the effects of submerged culture GA mycelium (GAM) and its active components (protocatechualdehyde [PCA]) on preadipocyte differentiation of 3T3-L1 cells. Mouse-derived preadipocyte 3T3-L1 cells were treated with differentiation inducers in the presence or absence of GAM extracts. We determined triglyceride accumulations, glycerol-3-phosphate dehydrogenase (GPDH) activities, and differentiation makers. PCA, the active component of GAM extract, was also used to treat 3T3-L1 cells. The MTT assay showed that the GAM extract (0.01-1 mg/mL) was not toxic to 3T3-L1 preadipocyte. Treatment of cells with GAM extracts and its active components significantly decreased the GPDH activity and lipid accumulation, a marker of adipogenesis, in a dose-dependent manner. Western blot analysis results showed that the protein expression levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1) were inhibited by the GAM extract. In addition, adipogenic-specific genes such as perilipin, fatty acid synthase (FAS), fatty acid transport protein 1 (FATP1), and fatty acid-binding protein 4 (FABP4) decreased in a dose-dependent manner. Quantitative high-performance liquid chromatography analysis showed that the GAM extract contained 1.14 mg/g PCA. GAM extracts suppressed differentiation of 3T3-L1 preadipocytes, in part, through altered regulation of PPARγ, C/EBPα, and SREBP1. These results suggest that GAM extracts and PCA may suppress adipogenesis by inhibiting differentiation of preadipocytes.
Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Ganoderma/química , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Regulação para Baixo/efeitos dos fármacos , Glicerolfosfato Desidrogenase/genética , Glicerolfosfato Desidrogenase/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Micélio/química , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/metabolismoRESUMO
Carnosol, an active constituent of rosemary, has been reported to possess anti-inflammatory and anticancer activities. However, the molecular mechanisms underlying the anticancer effects of carnosol remain poorly understood. In the present study, we found that carnosol significantly reduced the viability of human colon cancer (HCT116) cells in a concentration- and time-dependent manner. Treatment of cells with carnosol induced apoptosis, which was associated with activation of caspase-9 and -3 and the cleavage of poly-(ADP-ribose) polymerase (PARP). Incubation with carnosol elevated the expression of Bax and inhibited the levels of Bcl-2 and Bcl-xl. Carnosol induced expression of p53 and inhibited that of murine-double minute-2 (Mdm2). Moreover, carnosol generated reactive oxygen species (ROS), and pretreatment with N-acetyl cysteine abrogated carnosol-induced cleavage of caspase-3 and PARP. The constitutive phosphorylation, the DNA binding and reporter gene activity of signal transducer and activator of transcription-3 (STAT3) was diminished by treatment with carnosol. To further elucidate the molecular mechanisms of STAT3 inactivation, we found that carnosol attenuated the phosphorylation of Janus-activated kinase-2 (Jak2) and Src kinase. Pharmacological inhibition of Jak2 and Src inhibited STAT3 phosphorylation. Furthermore, carnosol attenuated the expression of STAT3 target gene products, such as survivin, cyclin-D1, -D2, and -D3. Taken together, our study provides the first report that carnosol induced apoptosis in HCT116 cells via generation of ROS, induction of p53, activation of caspases and inhibition of STAT3 signaling pathway.
Assuntos
Abietanos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Antineoplásicos/farmacologia , Caspase 3/biossíntese , Caspase 9/biossíntese , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/biossíntese , Ciclina D2/biossíntese , Ciclina D3/biossíntese , Proteínas de Ligação a DNA , Células HCT116 , Humanos , Proteínas Inibidoras de Apoptose/biossíntese , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/metabolismo , Fosforilação , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/biossíntese , Transdução de Sinais/efeitos dos fármacos , Survivina , Proteína Supressora de Tumor p53/biossíntese , Proteína X Associada a bcl-2/biossíntese , Proteína bcl-X/biossíntese , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/metabolismoRESUMO
Rosemary (Rosmarinus officinalis L.) has been used in folk medicine to treat headaches, epilepsy, poor circulation, and many other ailments. It was found that rosemary could act as a stimulant and mild analgesic and could reduce inflammation. However, the mechanisms underlying the anti-inflammatory effects of rosemary need more study to be established. Therefore, in this study, the effects of rosemary on the activation of nuclear factor kappa beta (NF-kB) and mitogen-activated protein kinases (MAPKs), the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)), and cytokine in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were investigated. A methanol extract of rosemary and its hexane fraction reduced NO generation with an IC(50) of 2.75 and 2.83 µg/ml, respectively. Also, the methanol extract and the hexane fraction inhibited LPS-induced MAPKs and NF-kB activation associated with the inhibition of iNOS or COX-2 expression. LPS-induced production of PGE(2) and tumour necrosis factor-alpha (TNF-α) were blocked by rosemary. Rosemary extract and its hexane fraction are important for the prevention of phosphorylation of MAPKs, thereby blocking NF-kB activation, which in turn leads to decreased expression of iNOS and COX-2, thus preventing inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Regulação para Baixo/efeitos dos fármacos , Inflamação/imunologia , Lipopolissacarídeos/imunologia , Extratos Vegetais/farmacologia , Rosmarinus/química , Linhagem Celular , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Humanos , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/imunologia , NF-kappa B/genética , NF-kappa B/imunologiaRESUMO
Atherosclerosis is a chronic and progressive inflammatory disease. Novel anti-inflammatory therapies may have promise as treatment strategies for cardiovascular risk reduction. Rosemary (Rosemarinus officinalis L.) has been used in folk medicine to treat headaches, epilepsy, poor circulation, and many other ailments. It was found that rosemary could act as a stimulant and mild analgesic and could reduce inflammation. However, the mechanisms underlying the anti-inflammatory and antiatherosclerotic effects of rosemary need more study. This study investigated effects of the rosemary components, carnosic acid (CA), and carnosol (CAR), on cell migration. Monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) were determined by Western blot and gelatin zymography, respectively, in RAW 264.7 macrophages and vascular smooth muscle cells (VSMCs). VSMC migration was assessed by a Matrigel migration assay. Active compounds of rosemary extracts were also analyzed using a reversed-phase high-performance liquid chromatography. MMP-9 and MCP-1 activities were markedly diminished with methanol extract (RM), n-hexane fraction (RH), and CA in RAW 264.7 cells. RM, RH, CA, and CAR suppressed tumor necrosis factor-alpha-induced VSMC migration by inhibiting MMP-9 expression. Chromatograms of RM- and RH-containing CA and CAR revealed higher CA contents of RM (9.4%, 93.85 µg/mg dry wt.) and, especially, RH (18.4%, 184.00 µg/mg dry wt.), which were appreciably elevated compared with the similar CAR content in RM and RH (3.7%, 37.30 µg/mg dry wt.; and 2.5%, 25.05 µg/mg dry wt., respectively). Rosemary, especially its CA component, has potential antiatherosclerosis effects related to cell migration.
Assuntos
Movimento Celular/efeitos dos fármacos , Quimiocina CCL2/genética , Metaloproteinase 9 da Matriz/genética , Miócitos de Músculo Liso/efeitos dos fármacos , Rosmarinus/química , Abietanos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Aterosclerose/tratamento farmacológico , Western Blotting , Linhagem Celular , Quimiocina CCL2/metabolismo , Cromatografia Líquida de Alta Pressão , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The antioxidant activities of fermented red ginseng (FRG) were investigated in vitro and in vivo. The contents of total polyphenol and total flavonoid in FRG extracts were 17.01±2.00 µg/mg and 18.42±3.97 µg/mg, respectively. These extracts were capable of directly scavenging α, α-diphenyl-picrylhydrazyl free radicals. The antioxidative effects of the FRG extracts in streptozotocin (STZ)-induced diabetic rats were also investigated. The activities of plasma alanine transaminase, aspartate transaminase, and γ-glutamyltransferase were significantly decreased by extract administration as compared to an STZ control group. Hepatic glutathione content depleted by STZ treatment was significantly increased by treatment of the FRG extracts, but the elevation of lipid peroxide content induced by STZ was significantly decreased by the extracts. Activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase decreased after STZ-treatment were recovered by the treatment of the FRG extracts. These results indicate that FRG extracts have antioxidative effets in STZ-induced diabetic rats.
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In the present study, the effect of an extract of immature Prunus salicina Lindl. cv. Soldam fruit on the viability and induction of apoptosis in human hepatocellular carcinoma HepG2 cells was investigated. The results showed that in comparison with other cancer cells, the growth inhibition exerted by immature plum extracts was greatest in HepG2. Apoptosis in HepG2 cells mediated by immature plums was associated with "death receptor signaling." Immature plum extracts significantly increased the activation of caspase-8, -10, and -3 and expression of the caspase-3 target proteins alpha-fodrin (induces membrane blebbing and cell shrinkage), poly(ADP-ribose) polymerase (a nuclear enzyme that is involved in DNA repair following DNA nicks), and DNA fragmentation factor (induces apoptotic DNA fragmentation). The total yield of identified polyphenols in immature plum extract was 10 g/kg dry weight. The major components, (-)-epicatechin and (-)-gallocatechin gallate, were 34.7% and 28.6% of total polyphenols, respectively. (+)-Catechin, (-)-epicatechin gallate, and (-)-catechin gallate were also found. On the basis of these results, the immature plum (P. salicina Lindl. cv. Soldam) and its active compound, (-)-epicatechin, are expected to be a natural resource for developing novel therapeutic agents for cancer prevention and treatment.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma/tratamento farmacológico , Catequina/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Extratos Vegetais/farmacologia , Prunus/química , Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma/metabolismo , Proteínas de Transporte/metabolismo , Caspases/metabolismo , Catequina/análise , Catequina/uso terapêutico , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/metabolismo , Frutas , Humanos , Neoplasias Hepáticas/metabolismo , Proteínas dos Microfilamentos/metabolismo , Extratos Vegetais/uso terapêutico , Poli(ADP-Ribose) Polimerases/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The goal of this study was to evaluate the anticancer effect of Prunus salicina Lindl. cv. Soldam at three maturity stages (immature, midmature and mature). In search for anticancer effects of immature plum extract (IPE), we have found its antimigrative property in (phorbol 12-myristate 13-acetate) PMA-induced HepG2 cells, and this effect is associated with inhibition of MMP-9 activity. IPE appeared to have a strong inhibitory effect on the PMA-induced MMP-9 secretion through suppression of the transcriptional activity of the MMP-9 gene independently of the TIMP gene in HepG2 cells. PMA induced the translocation of c-jun and p65 to the nucleus; however, IPE inhibited their nuclear translocations induced by PMA in HepG2 cells. These results clearly indicate that IPE suppresses both AP-1- and NF-kappaB-mediated MMP-9 gene transcriptional activity through inhibiting the nuclear translocations of AP-1 and NF-kappaB. These findings suggest that AP-1 and NF-kappaB activations through the ERK, p38 MAPK and JNK pathways appears to be required for the induction of MMP-9 expression by PMA in IPE, and IPE regulates PMA-stimulated MMP-9 expression by suppressing the p38 MAPK, JNK and ERK pathways. IPE leads to a decrease in the migration potential of HepG2 cells in vitro, and this suggests that the migration inhibition is correlated well with its inhibition of MMP-9 expression.
Assuntos
Carcinoma Hepatocelular/metabolismo , Expressão Gênica/efeitos dos fármacos , Metaloproteinase 9 da Matriz/genética , Extratos Vegetais/farmacologia , Prunus/química , Acetato de Tetradecanoilforbol/farmacologia , Transporte Biológico/efeitos dos fármacos , Western Blotting , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição AP-1/metabolismoRESUMO
In the present study, we investigated antimicrobial activity of Glycyrrhiza uralensis against various strains of methicillin-resistant Staphylococcus aureus (MRSA) (KCCM 11812, 40510, 40512). Glycyrrhiza uralensis was extracted by 80% MeOH and fractionated by organic solutions. The extract and fractions showed antimicrobial activity against standard S. aureus as well as MRSA. In the minimum inhibitory concentration test, G. uralensis showed 0.25 mg mL(-1) in hexane fraction and 0.10-0.12 mg mL(-1) in chloroform fraction. Especially, chloroform fraction showed 2.5 times higher antimicrobial activity than penicillin. Furthermore, chloroform fraction correlated with MRSA gene expression (MecA, MecI, MecRI, FemA). These results suggest that G. uralensis may have potent antimicrobial activity and thus, this medicinal herb can be a suitable phytotherapeutic agent for treating MRSA infections.
Assuntos
Glycyrrhiza uralensis/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Staphylococcus aureus Resistente à Meticilina/metabolismo , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Proteínas de Ligação às Penicilinas , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Proteínas Repressoras/biossíntese , Proteínas Repressoras/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Eclipta prostrata (Linn) has been used as a traditional medicinal plant to prevent lipidemia and atherosclerosis in Asia. However, its functional properties and the underlying mechanism of action have not been clearly defined. This study was conducted to elucidate the biological basis for hypolipidemic and antioxidant activities of E. prostrata. Charles River Sprague-Dawley CD rats (specific pathogen-free/viral antibody-free Crj/Bgi male, 180 +/- 10 g) were fed experimental diets supplemented with 0 mg (control), 25 mg (E25), 50 mg (E50), or 100 mg (E100) of a freeze-dried butanol fraction of E. prostrata per kilogram of diet for 6 weeks. Serum triacylglycerol and total cholesterol levels were significantly lower in the E50 and E100 groups by 9.8% to 19.0% and by 10.7% to 13.4%, respectively, and low-density lipoprotein-cholesterol levels were significantly reduced in the same groups by 10.3% to 13.0% compared with the untreated control group. The E50 and E100 groups also showed significantly increased high-density lipoprotein-cholesterol levels (13.0%-19.1%) compared with the control group. Atherogenic indices were decreased by 9.8% to 30.5% in all groups fed diets supplemented with E. prostrata. Furthermore, serum hydroxyl radical, lipid peroxide, and oxidized protein levels were significantly decreased in the E50 and E100 groups. These results clearly demonstrate the effects of E. prostrata on serum lipid and oxidative metabolism in rats. The health-promoting effects of E. prostrata, which were demonstrated in this study in a rat model, may have implications for atherosclerosis and hypercholesterolemia in humans.
Assuntos
Antioxidantes/análise , Eclipta/química , Lipídeos/sangue , Extratos Vegetais/administração & dosagem , Animais , Butanóis , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta , Radical Hidroxila/sangue , Peróxidos Lipídicos/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangueRESUMO
This study was carried out to investigate the chemopreventive effects of immature plum extracts. The methanol extract of immature plums (plum 1), that are picked at 20-40 days before final harvest, has remarkably inhibited the growth of hepatoma HepG2 cells. The effects of immature plum extracts on hepatotoxicity in benzo(alpha)pyrene (B(alpha)P, carcinogen)-treated mice were investigated. Male ICR mice were pretreated with immature plum extracts (2.5 or 5 g/kg bw/day, for 5 days, i.p.) before treatment with B(alpha)P(0.5 mg/kg bw, i.p., single dose). The activities of serum aminotransferase, cytochrome P450 (CYPs) and the hepatic content of lipid peroxide were increased on B(alpha)P-treatment group than control, but those levels were significantly decreased by the pretreatment of immature plum extracts. The primary CYPs involved in the metabolism and bioactivation of B(alpha)P are CYP1A1. The pretreatment of immature plum extracts inhibited the induction of CYP1A1 expression. The activities of glutathione peroxidase, superoxide dismutase and catalase were decreased by the pretreatment of immature plum extracts more than with B(alpha)P alone. Whereas, the hepatic content of glutathione and glutathione S-transferase activity depleted by B(alpha)P was significantly increased (p > 0.05). These results suggest that immature plum extracts may counteract toxic effects of carcinogens, such as B(alpha)P, and therefore possess the chemopreventive efficacy.
Assuntos
Anticarcinógenos/farmacologia , Carcinoma Hepatocelular/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Prunus/química , Animais , Benzo(a)pireno/toxicidade , Carcinógenos/toxicidade , Carcinoma Hepatocelular/induzido quimicamente , Catalase/metabolismo , Linhagem Celular Tumoral , Citocromo P-450 CYP1A1/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Relação Dose-Resposta a Droga , Frutas/química , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Peróxidos Lipídicos/metabolismo , Fígado/enzimologia , Neoplasias Hepáticas/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos ICR , Superóxido Dismutase/metabolismo , Transaminases/metabolismoRESUMO
This study was performed to investigate the effect of ethanol extract from Saururus chinensis (Lour.) Baill on liver function, plasma lipid composition and antioxidant system with high-fat diet for 4 weeks. Rats were divided into the following five groups; untreated control group (normal), treated with 0.5% SE (normal + 0.5% SE), high-fat group (high-fat), high-fat group treated with 0.1% SE (high-fat + 0.1% SE), or 0.5% SE (high-fat + 0.5% SE). Weight gains showed a tendency to decrease in rat with high-fat + SE. Plasma total cholesterol showed a tendency to decrease with ethanol extract from S. chinensis (Lour.) Baill. LDL-cholesterol contents were lower in ethanol extract group than that of control group. Aspartate amino transferase and alanine amino transferase activities were increased by high-fat diet, and were decreased by 0.5% SE. Lipid peroxide level showed a tendency to increase in high-fat diet group than that of normal group. In ethanol extract from S. chinensis (Lour.) Baill groups, lipid peroxide level decreased significantly and SOD activity was also decreased progressively. These results demonstrated that the ethanol extract of S. chinensis (Lour.) Baill lowered serum cholesterol levels, tissue lipid contents and accumulation of cholesterol in the rat.
Assuntos
Antioxidantes/metabolismo , Gorduras na Dieta/farmacologia , Etanol/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Extratos Vegetais/farmacologia , Saururaceae/química , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Colesterol/metabolismo , Dieta , Gorduras na Dieta/administração & dosagem , Relação Dose-Resposta a Droga , Flavonas/química , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Fenóis/química , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Baço/patologiaRESUMO
The goal of this study was to evaluate the anticancer effect of Prunus salicina Lindl. cv. Soldam at three maturity stages (immature, midmature and mature stages). Previous studies have shown that this fruit (plums) possesses hematopoiesis effects, prevents osteoporosis and has anti-mutagenic effects. An acetone extract of immature P. salicina Lindl. cv. Soldam fruit contained higher levels of total phenolics and condensed tannins than midmature and mature plums. The results showed that an acetone extract of immature plums possesses cytotoxic effects, which are related to the activity of the total polyphenols in the fruits. Apoptosis in MDA-MB-231 cells mediated by the immature plums was associated with an increase in Bax levels and a reduction in Bcl-2 levels and the cleavage of caspase 3, caspase 7, caspase 9 and poly-(ADP-ribose) polymerase. These results indicate that immature fruit of P . salicina Lindl. cv. Soldam can be regarded as a safe and promising new dietary source for decreasing the risk of developing breast cancer.