RESUMO
CONTEXT: Seaweeds are rich in bioactive compounds in the form of vitamins, phycobilins, polyphenols, carotenoids, phycocyanins and polysaccharides; many of these are known to have advantageous applications in human health. 3-Hydroxy-4,7-megastigmadien-9-one (comp) was isolated from Ulva pertusa (U. pertusa) Kjellman (Ulvaceae), which is a familiar edible green seaweed. OBJECTIVE: This study evaluates the anti-inflammatory activity of comp in CpG DNA-stimulated bone marrow-derived dendritic cells (BMDCs). MATERIALS AND METHODS: For evaluating the effect of comp on cytokines production, BMDCs were treated with doses of comp (0, 0.5, 1, 2, 5, 10, 25 and 50 µM) for 1 h before stimulation with CpG DNA (1 µM). Cytokine production was measured by ELISA. Western blotting was conducted for evaluating effect of comp (50 µM) on MAPKs and NF-κB pathways. Luciferase reporter gene assay was conducted for effect of comp (0, 5, 10 and 25 µM) on transcriptional activity of AP-1 and NF-κB. RESULTS: Comp exhibited strong inhibition of interleukin (IL)-12 p40, IL-6 and TNF-α cytokine production with IC50 values of 6.02 ± 0.35, 27.14 ± 0.73, and 7.56 ± 0.21 µM, respectively. It blocked MAPKs and NF-κB pathways by inhibiting the phosphorylation of ERK1/2, JNK1/2, p38 and IκBα. In addition, it strongly inhibited the transcriptional activity of AP-1 and NF-κB with IC50 values of 8.74 ± 0.31 and 12.08 ± 0.24 µM, respectively. DISCUSSION AND CONCLUSION: Taken together, these data suggest that comp has a significant anti-inflammatory property and warrants further studies concerning the potential of comp for medicinal use.
Assuntos
Anti-Inflamatórios/farmacologia , Células Dendríticas/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Norisoprenoides/farmacologia , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor Toll-Like 9/antagonistas & inibidores , Ulva/química , Animais , Anti-Inflamatórios/isolamento & purificação , Ilhas de CpG , Citocinas/metabolismo , Células Dendríticas/enzimologia , Relação Dose-Resposta a Droga , Ativação Enzimática , Feminino , Genes Reporter , Células HEK293 , Humanos , Mediadores da Inflamação/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Norisoprenoides/isolamento & purificação , Oligonucleotídeos/genética , Oligonucleotídeos/metabolismo , Fosforilação , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Fatores de Tempo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Transcrição Gênica/efeitos dos fármacos , TransfecçãoRESUMO
This study was intended to assess the anti-inflammatory properties of 4-hydroxy-2,3-dimethyl-2-nonen-4-olide (Comp) isolated from Ulva pertusa Kjellman on production of pro-inflammatory cytokines. Comp revealed remarkable inhibitory effects on production of pro-inflammatory cytokines in bone marrow-derived dendritic cells (BMDCs). Comp pre-treatment in the CpG DNA-stimulated BMDCs exhibited strong inhibition of interleukin (IL)-12 p40 and IL-6 production with IC50 values ranging from 7.57 ± 0.2 to 10.83 ± 0.3, respectively. It revealed an inhibitory effect on the phosphorylation of ERK1/2, JNK1/2, and p38, and on activator protein (AP)-1 reporter activity. Comp displayed noteworthy inhibitory effects on phosphorylation and degradation of IκBα, and on NF-κB reporter activity. In summary, these data propose that Comp has substantial anti-inflammatory properties and warrants further study concerning its potential use as a therapeutic agent for inflammation-associated maladies.
Assuntos
Anti-Inflamatórios/farmacologia , Medula Óssea/efeitos dos fármacos , Ilhas de CpG/efeitos dos fármacos , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Inflamação/tratamento farmacológico , Ulva/química , Animais , Feminino , Interleucina-12/metabolismo , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismoRESUMO
Isorhamnetin (3-methylquercetin) is a flavonoid derived from the fruits of certain medicinal plants. This study investigated the photoprotective properties of isorhamnetin against cell damage and apoptosis resulting from excessive ultraviolet (UV) B exposure in human HaCaT keratinocytes. Isorhamnetin eliminated UVB-induced intracellular reactive oxygen species (ROS) and attenuated the oxidative modification of DNA, lipids, and proteins in response to UVB radiation. Moreover, isorhamnetin repressed UVB-facilitated programmed cell death in the keratinocytes, as evidenced by a reduction in apoptotic body formation, and nuclear fragmentation. Additionally, isorhamnetin suppressed the ability of UVB light to trigger mitochondrial dysfunction. Taken together, these results indicate that isorhamnetin has the potential to protect human keratinocytes against UVB-induced cell damage and death.
RESUMO
CONTEXT: Our previous work demonstrated that an ethyl acetate extract derived from Sargassum muticum (Yendo) Fenshol (SME) protected human HaCaT keratinocytes against ultraviolet B (UVB)-induced oxidative stress by increasing antioxidant activity in the cells, thereby inhibiting apoptosis. OBJECTIVE: The aim of the current study was to further elucidate the anti-apoptotic mechanism of SME against UVB-induced cell damage. MATERIALS AND METHODS: The expression levels of several apoptotic-associated and mitogen-activated kinase (MAPK) signaling proteins were determined by western blot analysis of UVB-irradiated HaCaT cells with or without prior SME treatment. In addition, the loss of mitochondrial membrane potential (Δψm) was detected using flow cytometry or confocal microscopy and the mitochondria membrane-permeate dye, JC-1. Apoptosis was assessed by quantifying DNA fragmentation and apoptotic body formation. Furthermore, cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. RESULTS: SME absorbed electromagnetic radiation in the UVB range (280-320 nm) of the UV/visible light spectrum. SME also increased Bcl-2 and Mcl-1 expression in UVB-irradiated cells and decreased the Bax expression. Moreover, SME inhibited the UVB-induced disruption of mitochondrial membrane potential and prevented UVB-mediated increases in activated caspase-9 and caspase-3 (an apoptotic initiator and executor, respectively) levels. Notably, treatment with a pan-caspase inhibitor enhanced the anti-apoptotic effects of SME in UVB-irradiated cells. Finally, SME reduced the UVB-mediated phosphorylation of p38 MAPK and JNK, and prevented the UVB-mediated dephosphorylation of Erk1/2 and Akt. DISCUSSION AND CONCLUSION: The present results indicate that SME safeguards HaCaT keratinocytes from UVB-mediated apoptosis by inhibiting a caspase-dependent signaling pathway.
Assuntos
Apoptose/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sargassum/química , Acetatos/química , Apoptose/efeitos da radiação , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Fragmentação do DNA/efeitos da radiação , Citometria de Fluxo , Humanos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Microscopia Confocal , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Raios Ultravioleta/efeitos adversosRESUMO
DWP208 is a sodium succinate form of ZYM-201 which is a triterpenoid glycoside isolated from Sanguisorba officinalis, a medicinal plant prescribed for various diseases, such as duodenal ulcers and bleeding in East Asian counties. We demonstrated that this compound is able to normalize the altered lipid metabolism induced by hyperglycemia and a high fat diet. In this study, we determined whether hyperlipidemic conditions induced with chronically treated alcohol can also be restored by DWP208. Similar to our previous results, orally administered DWP208 (1 to 10 mg/kg) also ameliorated the hyperlipidemia that was induced by alcohol. This compound reversed the alcohol-induced hyperlipidemia including (i) up-regulated hyperlipidemic parameters such as low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), atherosclerotic index (AI), triglyceride, and total cholesterol, and (ii) down-regulated hyperlipidemic parameters such as absolute body weight, superoxide dismutase (SOD) activity, and high-density lipoprotein (HDL) in serum and liver. According to our data, the ameliorative activity of DWP208 is due to its indirect anti-oxidative activity as a result of which lipid peroxide and hydroxyl radical levels were reduced and the activity of SOD was enhanced. Therefore, our data strongly suggest that DWP208 can be used as a remedy against alcohol-induced hyperlipidemia.
RESUMO
Sargassum muticum (S. muticum) is a brown edible alga and widely distributed in Korea. This report was designed to evaluate the anti-inflammatory properties of apo-9'-fucoxanthinone (APO-9') isolated from S. muticum on pro-inflammatory cytokine production. S. muticum extract (SME) exhibited significant inhibitory effects on pro-inflammatory cytokine production in bone marrow-derived macrophages (BMDMs) and dendritic cells (BMDCs). APO-9' pre-treatment in the CpG DNA-stimulated BMDMs and BMDCs showed a strong dose-dependent inhibitory effect on interleukin (IL)-12 p40, IL-6 and tumor necrosis factor (TNF)-α production with IC50 values ranging from 5.31 to 13.79. It exhibited a strong inhibitory effect on the phosphorylation of ERK1/2 and on activator protein (AP)-1 reporter activity. APO-9' pre-treatment exhibited significant inhibition of CpG DNA-induced production of inducible nitric oxide synthase. Taken together, these data suggest that SME and APO-9' have a significant anti-inflammatory property and warrant further studies concerning the potentials of SME and APO-9' for medicinal use.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sargassum/química , Animais , Linhagem Celular , Ilhas de CpG/efeitos dos fármacos , Células HEK293 , Humanos , Proteínas I-kappa B/metabolismo , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Phaeophyceae/química , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismoRESUMO
The aim of this study was to investigate the protective effects of the ethanol extract of the red algae Chondracanthus tenellus (Harvey) Hommersand (CTE) on cultured human keratinocyte cell line. The cellular protection conferred by CTE was evidenced by the ability of the extract to absorb ultraviolet B (UVB; 280-320 nm) and to scavenge the radical 1,1-diphenyl-2-picrylhydrazyl, as well as intracellular reactive oxygen species (ROS), induced by either hydrogen peroxide (H(2)O(2)) or UVB radiation. In addition, both superoxide anion generated by the xanthine/xanthine oxidase system and hydroxyl radical generated by the Fenton reaction (FeSO(4) + H(2)O(2)) were scavenged by CTE, as confirmed using electron spin resonance spectrometry. In the human keratinocyte cell line, CTE decreased the degree of injury resulting from UVB-induced oxidative stress to lipids, proteins, and DNA. CTE-treated cells also showed a reduction in UVB-induced apoptosis, as exemplified by fewer apoptotic bodies and less DNA fragmentation. Taken together, these results suggest that CTE confers protection on the human keratinocyte cell line against UVB-induced oxidative stress by absorbing UVB ray and scavenging ROS, thereby reducing injury to cellular constituents.
Assuntos
Radicais Livres , Queratinócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rodófitas/química , Raios Ultravioleta , Linhagem Celular , Espectroscopia de Ressonância de Spin Eletrônica , HumanosRESUMO
A new cyclic tetrapeptide (1), along with known congeners (2, 3), was isolated from the fungus Phoma sp. derived from the giant jellyfish Nemopilema nomurai. The absolute configuration of 1 was determined using the modified Mosher's method and Marfey's method. Compound 1 displayed a weak suppressive effect on the production of nitric oxide (NO) in murine macrophage cells (RAW264.7) without notable cytotoxicity.
Assuntos
Ascomicetos/química , Peptídeos Cíclicos/isolamento & purificação , Cifozoários/microbiologia , Animais , Linhagem Celular , Camundongos , Modelos Moleculares , Conformação Molecular , Peptídeos Cíclicos/químicaRESUMO
This study was conducted to evaluate the effect of Acanthopanax koreanum and acankoreoside J from A. koreanum on the promotion of hair growth. When immortalized rat vibrissa dermal papilla cells were treated with extract of A. koreanum leaves, the proliferation of dermal papilla cells significantly increased. In particular, acankoreoside J among several components, isolated from A. koreanum leaves, markedly promoted the proliferation of the dermal papilla cells. When rat vibrissa follicles were treated with an acankoreoside J, the hair-fiber lengths of the vibrissa follicles increased significantly. We further investigated ß-catenin pathway and cell cycle regulation with respect to the effect of acankoreoside J on the proliferation of the dermal papilla cells. Treatment with acankoreoside J results in an increase of nuclear ß-catenin level, and up-regulation of cyclin D1, cyclin E and CDK2, whereas, the expression of p27(kip1) was down-regulated in the dermal papilla cells. Taken together, these results suggest that acankoreoside J, a lupane-triterpene of A. koreanum, has the potential of promoting hair growth by promoting cell cycle progression of the dermal papilla cells, through the increase of nuclear ß-catenin, along with the up-regulation of cyclin D1, cyclin E and CDK2, and down-regulation of p27(kip1).
Assuntos
Eleutherococcus/química , Glicosídeos/farmacologia , Cabelo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Glicosídeos/isolamento & purificação , Cabelo/crescimento & desenvolvimento , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Masculino , Folhas de Planta , Ratos , Ratos Wistar , Triterpenos/isolamento & purificação , Regulação para Cima/efeitos dos fármacos , Vibrissas , beta Catenina/metabolismoRESUMO
Adipocyte dysfunction is associated with the development of obesity. In this study, artemisinic acid, which was isolated from Artemisia annua L., inhibited adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAMSCs) and its mechanism of action was determined. The mRNA levels of peroxidase proliferation-activated receptor (PPAR) γ and CCAAT/enhancer binding protein (C/EBP) α, late adipogenic factors, were reduced by artemisinic acid. Moreover, the mRNA levels of the PPAR γ target genes lipoprotein lipase, CD36, adipocyte protein, and liver X receptor were down-regulated by artemisinic acid. Artemisinic acid reduced expression of the C/EBP δ gene without impacting C/EBP ß. In addition, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that reduced expression of the C/EBP δ gene was mediated by inhibiting Jun N-terminal kinase (JNK). Additionally, artemisinic acid also reduced the expression of the adipogenesis-associated genes glucose transporter-4 and vascular endothelial growth factor. In addition to the interference of artemisinic acid with adipogenesis, artemisinic acid significantly attenuated tumor necrosis factor-α-induced secretion of interleukin-6 by undifferentiated hAMSCs, thus influencing insulin resistance and the inflammatory state characterizing obesity. Taken together, these findings indicate that inhibiting adipogenic differentiation of hAMSCs by artemisinic acid occurs primarily through reduced expression of C/EBP δ, which is mediated by the inhibition of JNK and suggest that aremisinic acid may be used as a complementary treatment option for obesity associated with metabolic syndrome.
Assuntos
Adipogenia/efeitos dos fármacos , Artemisininas/farmacologia , Proteína delta de Ligação ao Facilitador CCAAT/biossíntese , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Obesidade/tratamento farmacológico , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/fisiologia , Antígenos CD36/biossíntese , Antígenos CD36/genética , Diferenciação Celular , Linhagem Celular , Regulação para Baixo , Medicamentos de Ervas Chinesas/farmacologia , Proteínas de Ligação a Ácido Graxo/biossíntese , Proteínas de Ligação a Ácido Graxo/genética , Transportador de Glucose Tipo 4/biossíntese , Humanos , Resistência à Insulina , Interleucina-6/biossíntese , Interleucina-6/metabolismo , Lipase Lipoproteica/biossíntese , Lipase Lipoproteica/genética , Receptores X do Fígado , Células-Tronco Mesenquimais/fisiologia , Receptores Nucleares Órfãos/biossíntese , Receptores Nucleares Órfãos/genética , PPAR gama/biossíntese , PPAR gama/genética , RNA Mensageiro/biossíntese , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossínteseRESUMO
ZYM-201 is a methyl ester of a novel triterpenoid glycoside. It is isolated from SANGUISORBA OFFICINALIS, a widely used medicinal plant in Korea, China, and Japan, that is prescribed for various diseases such as diarrhea, chronic intestinal infections, duodenal ulcers, and bleeding. In this study, the antihyperlipidemic effect of the salt form (sodium succinate) of ZYM-201 was examined using streptozotocin (STZ)-treated hyperglycemic rats. Oral administration of ZYM-201 sodium succinate (3 to 10 mg/kg) resulted in recovery of the increased serum levels of triglyceride (TG) and total cholesterol (TC) back to normal levels. Elevated levels of serum lipoproteins, such as high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), were also significantly restored by this compound without altering 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity. Finally, ZYM-201 sodium succinate displayed antioxidative properties, including suppression of lipid peroxide and hydroxyl radical generation and upregulation of superoxide dismutase (SOD) activity. Therefore, our data strongly suggest that ZYM-201 sodium succinate can be used as a remedy for the treatment of diabetes-derived hyperlipidemic disorders such as atherosclerosis and vascular diseases.
Assuntos
Antioxidantes/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Glicosídeos/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Fitoterapia , Sanguisorba/química , Triterpenos/uso terapêutico , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Complicações do Diabetes/sangue , Complicações do Diabetes/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Radical Hidroxila/metabolismo , Hiperlipidemias/sangue , Hiperlipidemias/induzido quimicamente , Hipolipemiantes/isolamento & purificação , Hipolipemiantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Estreptozocina , Superóxido Dismutase/metabolismo , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
The aim of this study was to investigate the cytoprotective properties of the ethyl acetate fraction of Sargassum muticum (SME) against ultraviolet B (UVB)-induced cell damage in human keratinocytes (HaCaT cells). SME exhibited scavenging activity toward the 1,1-diphenyl-2-picrylhydrazyl radicals and hydrogen peroxide (H(2)O(2)) and UVB-induced intracellular reactive oxygen species (ROS). SME also scavenged the hydroxyl radicals generated by the Fenton reaction (FeSO(4) + H(2)O(2)), which was detected using electron spin resonance spectrometry. In addition, SME decreased the level of lipid peroxidation that was increased by UVB radiation, and restored the level of protein expression and the activities of antioxidant enzymes that were decreased by UVB radiation. Furthermore, SME reduced UVB-induced apoptosis as shown by decreased DNA fragmentation and numbers of apoptotic bodies. These results suggest that SME protects human keratinocytes against UVB-induced oxidative stress by enhancing antioxidant activity in cells, thereby inhibiting apoptosis.
Assuntos
Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Extratos Vegetais/farmacologia , Protetores contra Radiação/farmacologia , Sargassum/química , Raios Ultravioleta/efeitos adversos , Acetatos , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/metabolismo , Catalase/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Picratos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Sanguisorba officinalis, a well known and valuable medicinal plant in Korea, China and Japan has been used traditionally for the treatment of inflammatory and metabolic diseases such as diarrhea, chronic intestinal infections, duodenal ulcers, and bleeding. We studied the anti-hyperlipidemic effects of a chemically modified triterpenoid glycoside (ZYM-201 sodium succinate) isolated from Sanguisorba officinalis in rats in which hyperlipidemia had been induced by dietary administration of cholesterol and cholic acid. Oral administration of ZYM-201 sodium succinate (1 to 10 mg/kg) dose-dependently attenuated the diet-induced increases in body and liver weights. At 10 mg/kg, this compound also reversed the enhancement of serum levels of triglycerides (TG) and total cholesterol back to normal levels. In addition, imbalances in both serum and hepatic values of high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) were prevented. Finally, this compound both blocked the generation of lipid peroxide and hydroxyl radicals and enhanced the activity of superoxide dismutase (SOD) in liver. Therefore, our data strongly suggest that ZYM-201 sodium succinate could play a role in modulating hyperlipidemic conditions, which could be used as a valuable remedy for the treatment of relevant disorders such as atherosclerosis and vascular diseases.
Assuntos
Dieta , Glicosídeos/farmacologia , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes , Triterpenos/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colesterol/sangue , Colesterol na Dieta/farmacologia , Gorduras na Dieta/farmacologia , Humanos , Radical Hidroxila/metabolismo , Lipase/sangue , Lipoproteínas/sangue , Fígado/efeitos dos fármacos , Masculino , Camundongos , Óxido Nítrico/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Colato de Sódio/farmacologia , Triglicerídeos/sangue , Células U937RESUMO
The aim of this study was to investigate the antioxidant properties of the ethanol extract of the flower of Camellia japonica (Camellia extract). Camellia extract exhibited 1,1-diphenyl-2-picrylhydrazyl radical and intracellular reactive oxygen species (ROS) scavenging activity in human HaCaT keratinocytes. In addition, Camellia extract scavenged superoxide anion generated by xanthine/xanthine oxidase and hydroxyl radical generated by the Fenton reaction (FeSO(4) + H(2)O(2)) in a cell-free system, which was detected by electron spin resonance spectrometry. Furthermore, Camellia extract increased the protein expressions and activity of cellular antioxidant enzymes, such as superoxide dismutase, catalase and glutathione peroxidase. These results suggest that Camellia extract exhibits antioxidant properties by scavenging ROS and enhancing antioxidant enzymes. Camellia extract contained quercetin, quercetin-3-O-glucoside, quercitrin and kaempferol, which are antioxidant compounds.
Assuntos
Antioxidantes/química , Camellia/química , Oxirredutases/metabolismo , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Camellia/metabolismo , Catalase/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Etanol/química , Flores/química , Flores/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Extratos Vegetais/farmacologia , Superóxido Dismutase/metabolismoRESUMO
Fucoidan, a sulfated polysaccharide, has various biological activities, such as anticancer, antiangiogenic and antiinflammatory effects; however, the mechanisms of action of fucoidan on anticancer activity have not been fully elucidated. The anticancer effects of fucoidan from Undaria pinnatifida on A549 human lung carcinoma cells were examined. Treatment of A549 cells with fucoidan resulted in potent antiproliferative activity. Also, some typical apoptotic characteristics, such as chromatin condensation and an increase in the population of sub-G1 hypodiploid cells, were observed. With respect to the mechanism underlying the induction of apoptosis, fucoidan reduced Bcl-2 expression, but the expression of Bax was increased in a dose-dependent manner compared with the controls. Furthermore, fucoidan induced caspase-9 activation, but decreased the level of procaspase-3. Cleavage of poly-ADP-ribose polymerase (PARP), a vital substrate of effector caspase, was found. The study further investigated the role of the MAPK and PI3K/Akt pathways with respect to the apoptotic effect of fucoidan, and showed that fucoidan activates ERK1/2 in A549 cells. Unlike ERK1/2, however, treatment with fucoidan resulted in the down-regulation of phospho-p38 expression. In addition, fucoidan resulted in the down-regulation of phospho-PI3K/Akt. Together, these results indicate that fucoidan induces apoptosis of A549 human lung cancer cells through down-regulation of p38, PI3K/Akt, and the activation of the ERK1/2 MAPK pathway.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Polissacarídeos/farmacologia , Undaria/química , Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/patologiaRESUMO
New 15-keto-prostaglandins (1-4) were isolated from the MeOH extract of the red alga, Gracilaria verrucosa. Their structures were determined to be prostaglandin B congeners (1-3) and a prostaglandin E congener (4) based on the NMR and MS data. Prostaglandins with a C-15 keto function are rare from natural sources. The presence of these metabolites in the alga is notable because 15-keto-prostaglandins (15-keto-PGs) are considered to be the metabolic products of regular prostaglandins in mammals. The occurrence of different prostaglandins in this alga might be due to the existence of different oxidative enzymes, as previously mentioned for oxygenated fatty acids of the red alga Gracilariopsis lemaneiformis. The antiinflammatory activity of these prostaglandins was examined by evaluating their inhibitory effects on nitric oxide production in lipopolysaccharide (LPS)-activated RAW264.7 murine macrophage cells. These prostaglandins showed weak activity on nitric oxide production.
Assuntos
Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/química , Descoberta de Drogas , Gracilaria/química , Prostaglandinas/análise , Prostaglandinas/química , Alprostadil/análogos & derivados , Alprostadil/análise , Alprostadil/química , Alprostadil/isolamento & purificação , Alprostadil/farmacologia , Animais , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Prostaglandinas/isolamento & purificação , Prostaglandinas/farmacologia , Prostaglandinas B/análise , Prostaglandinas B/química , Prostaglandinas B/isolamento & purificação , Prostaglandinas B/farmacologia , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosRESUMO
This study was conducted to evaluate the effect of Crinum asiaticum, a plant native to Jeju Island, Korea, on the promotion of hair growth. When rat vibrissa follicles were treated with a 95% ethanol (EtOH) extract of C. asiaticum, the hair-fiber lengths of the vibrissa follicles increased significantly. In addition, after daily topical application of the EtOH extract of C. asiaticum onto the back of C57BL/6 mice, anagen progression of the hair shaft was induced. Moreover, the extract increased the proliferation of immortalized vibrissa dermal papilla cells. When the vibrissa follicles in the anagen phase were treated with the extract, immunohistochemical analysis revealed that the extract was found to increase the expression of proliferating cell nuclear antigen (PCNA) in the bulb region of the 7-day cultured follicles. In particular, norgalanthamine, a principal of the extract, showed activity that increased the hair-fiber lengths of vibrissa follicles and the proliferation of dermal papilla cells. These results suggest that norgalanthamine, a principal of C. asiaticum, has the potential to promote hair growth via the proliferation of dermal papilla.
Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Crinum , Galantamina/análogos & derivados , Cabelo/crescimento & desenvolvimento , Extratos Vegetais/farmacologia , Animais , Células Cultivadas , Citoproteção/efeitos dos fármacos , Feminino , Galantamina/farmacologia , Cabelo/efeitos dos fármacos , Folículo Piloso/citologia , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Minoxidil/farmacologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Wistar , VibrissasRESUMO
Lindera erythrocarpa Makino (Lauraceae) is used as a traditional medicine for analgesic, antidote, and antibacterial purposes and shows anti-tumor activity. We studied the effects of Lindera erythrocarpa on the human ether-a-go-go-related gene (HERG) channel, which appears of importance in favoring cancer progression in vivo and determining cardiac action potential duration. Application of MeOH extract of Lindera erythrocarpa showed a dose-dependent decrease in the amplitudes of the outward currents measured at the end of the pulse (I(HERG)) and the tail currents of HERG (I(tail)). When the BuOH fraction and H(2)O fraction of Lindera erythrocarpa were added to the perfusate, both I(HERG) and I(tail) were suppressed, while the hexane fraction, CHCl(3) fraction, and EtOAc fraction did not inhibit either I(HERG) or I(tail). The potential required for half-maximal activation caused by EtOAc fraction, BuOH fraction, and H(2)O fraction shifted significantly. The BuOH fraction and H(2)O fraction (100 microg/mL) decreased g(max) by 59.6% and 52.9%, respectively. The H(2)O fraction- and BuOH fraction-induced blockades of I(tail) progressively decreased with increasing depolarization, showing the voltage-dependent block. Our findings suggest that Lindera erythrocarpa, a traditional medicine, blocks HERG channel, which could contribute to its anticancer and cardiac arrhythmogenic effect.
Assuntos
Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Lindera/química , Extratos Vegetais/metabolismo , Bloqueadores dos Canais de Potássio/metabolismo , Animais , Butanóis/química , Butanóis/metabolismo , Canais de Potássio Éter-A-Go-Go/metabolismo , Feminino , Humanos , Oócitos/citologia , Oócitos/fisiologia , Técnicas de Patch-Clamp , Xenopus laevisRESUMO
The antitumor activity of fucoidan from Fucus vesiculosus was investigated in human colon carcinoma cells. The crude fucoidan, a polysaccharide composed predominantly of sulfated fucose, markedly inhibited the growth of HCT-15 cells (human colon carcinoma cells). After HCT-15 cells were treated with fucoidan, several apoptotic events such as DNA fragmentation, chromatin condensation and increase of the population of sub-G1 hypodiploid cells were observed. In the mechanism of fucoidan-induced apoptosis, we examined changes in Bcl-2 and Bax protein expression levels and activation of caspases. Fucoidan decreased Bcl-2 expression, whereas the expression of Bax was increased in a time-dependent manner compared to the control. In addition, the active forms of caspase-9 and caspase-3 were increased, and the cleavage of poly(ADP-ribose) polymerase (PARP), a vital substrate of effector caspase, was observed. Furthermore, the induction of apoptosis was also accompanied by a strong activation of extracellular signal-regulated kinase (ERK) and p38 kinase and an inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt in a time-dependent manner. These findings provide evidence demonstrating that the pro-apoptotic effect of fucoidan is mediated through the activation of ERK, p38 and the blocking of the PI3K/Akt signal pathway in HCT-15 cells. These data support the hypothesis that fucoidan may have potential in colon cancer treatment.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Fucus/química , Extratos Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Antineoplásicos Fitogênicos/farmacologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
This study was conducted to evaluate the effect of Schisandra nigra, a plant native to Jeju Island, South Korea, on the promotion of hair growth. When rat vibrissa follicles were treated with 85% ethanol (EtOH) extract of S. nigra, the hair-fiber lengths of the vibrissa follicles increased significantly. In addition, after topical application of the EtOH extract of S. nigra onto the back of C57BL/6 mice every other day, anagen progression of the hair shaft was induced. Moreover, the extract increased both the expression of proliferating cell nuclear antigen (PCNA) in the bulb matrix region and the proliferation of immortalized vibrissa dermal papilla cells. In order to determine the mechanism by which S. nigra promotes hair growth, we examined its relationship with the transforming growth factor-beta2 (TGF-beta2) signal pathway, which is known to be a regulator of catagen induction. When the vibrissa follicles in the anagen phase were treated with S. nigra extract for 7 days, the expression of TGF-beta2 in the bulb matrix region was found to be lower than that of the control follicles that were expected to be in the anagen-catagen transition phase. These results suggest that S. nigra extract has the potential to promote hair growth via down regulation of TGF-beta2 and the proliferation of dermal papilla.