RESUMO
BACKGROUND: Investigating neural correlates in recovered patients with psychosis is important in terms of identifying biological markers associated with recovery status or predicting a possible future relapse. We sought to examine thalamic nuclei volumes and thalamus-centered functional connectivity (FC) in recovered patients with psychosis who discontinued their medication. METHODS: Thirty patients with psychosis who satisfied the criteria for full recovery and 50 healthy controls (HC) matched for age, sex, and education underwent magnetic resonance imaging and clinical evaluation. The recovered patients were divided into the maintained and relapsed subjects according to their clinical status on the follow-ups. Thalamic nuclei volumes and thalamus-centered FC were measured between the recovered patients and HC. Correlations between the thalamic nuclei or altered FC, and clinical symptoms and cognitive functioning were explored. RESULTS: Modest cognitive impairments and reduced thalamic nuclei volumes were evident in the recovered patients. Moreover, we found altered thalamo-cortical connectivity and its associations with negative symptoms and cognitive functioning in the recovered patients compared with HC. CONCLUSION: These findings suggest that there are still cognitive impairments, and aberrant neuronal changes in the recovered patients. The implication of differential FC patterns between the maintained and the relapsed patients remain to be further explored.
Assuntos
Disfunção Cognitiva , Transtornos Psicóticos , Humanos , Transtornos Psicóticos/complicações , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/patologia , Tálamo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Cognição , Vias Neurais/diagnóstico por imagemRESUMO
Virtual reality (VR) technology can be a supporting tool to enhance mindfulness. Recently, many research using VR-based mindfulness (VBM) has been carried out in various psychiatric disorders but not in psychosis. We investigated safety and effects of virtual reality-based mindfulness (VBM) in patients with psychosis as a pilot study. Sixty-four patients were randomly assigned to VBM or to VR control. For VBM, education and meditation videos were provided. For VR control, 3-dimensional natural scenes were shown. Both programs consisted of 8 weekly sessions, each lasting about 30 min. Pre- and post-assessments were performed using the experiences questionnaire (EQ), psychotic symptom rating scales-delusion (PSYRATS-D), PSYRATS-auditory hallucinations (AH), motivation and pleasure scale-self rating (MAP-SR) and etc. The safety questionnaire was also surveyed after 1st and 8th session. Physiological measures such as skin conductance level (SCL), heart rate (HR) and RR interval, were collected during the VR interventions. Limited individuals participated in the safety questionnaire and physiological measures. All the results were presented in mean and standard deviation. We did not observe significant results in group x time interaction and main effects of group and time in the decentering and clinical scales. However, within group comparison showed that patients randomized to VBM showed increased decentering (p = 0.029) and decreased amount (p = 0.032) and duration of preoccupation (p = 0.016) in the PSYRATS-D. For the feelings and motivations about close caring relationships of the MAP-SR, we observed a significant group x time interaction (p = 0.027). The frequency of VR sickness was high but its severity was mild. There were significant differences only in HR over time in the VBM group (p = 0.01). These results suggest that VBM was not more effective in reducing decentering and psychiatric symptoms than VR control but its adversity was modest.
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BACKGROUND: Few studies have investigated functional connectivity (FC) in patients with psychotic disorder not otherwise specified (PNOS). We sought to identify distinct FC differentiating PNOS from schizophrenia (SZ). METHODS: In total, 49 patients with PNOS, 42 with SZ, and 55 healthy controls (HC) matched for age, sex, and education underwent functional magnetic resonance imaging (fMRI) brain scans and clinical evaluation. Using six functional networks consisting of 40 regions of interest (ROIs), we conducted ROI to ROI and intra- and inter-network FC analyses using resting-state fMRI (rs-fMRI) data. Correlations of altered FC with symptomatology were explored. RESULTS: We found common brain connectomics in PNOS and SZ including thalamo-cortical (especially superior temporal gyrus) hyperconnectivity, thalamo-cerebellar hypoconnectivity, and reduced within-thalamic connectivity compared to HC. Additionally, features differentiating the two patient groups included hyperconnectivity between the thalamic subregion and anterior cingulate cortex in PNOS compared to SZ and hyperconnectivity of the thalamic subregions with the posterior cingulate cortex and precentral gyrus in SZ compared to PNOS. CONCLUSIONS: These findings suggest that PNOS and SZ exhibit both common and differentiating changes in neuronal connectivity. Furthermore, they may support the hypothesis that PNOS should be treated as a separate clinical syndrome with distinct neural connectomics.
Assuntos
Conectoma , Transtornos Psicóticos , Esquizofrenia , Humanos , Mapeamento Encefálico , Tálamo/diagnóstico por imagem , Conectoma/métodos , Imageamento por Ressonância Magnética , EncéfaloRESUMO
Spirulina maxima is a marine microalga that has been promoted worldwide as a super food. This study was conducted to evaluate its ability to improve memory in the older adults using Spirulina maxima 70% ethanol extract (SM70EE). This randomized, double-blind, placebo-controlled clinical trial comprised 80 volunteers recruited from Jeonbuk National University Hospital in Jeonju, Republic of Korea, who were randomly assigned to two groups. The participants received either 1 g/day of SM70EE or a placebo without otherwise changing their diet or physical activity. The participants were examined at baseline and after a 12-week interval to determine whether there were changes in their results for visual learning, visual working memory, and verbal learning tests from the Korean version of the Montreal Cognitive Assessment, brain-derived neurotrophic factor and beta-amyloid levels, and total antioxidant capacity. Compared to the placebo group, the treatment group showed a significant improvement in visual learning and visual working memory test results and enhanced vocabulary. SM70EE use was shown to improve memory, with no adverse effects. Its efficacy in alleviating Alzheimer's disease symptoms was verified for the first time through this clinical trial. SM70EE could play a role in the management of patients with dementia. This trial is registered with registration number of clinical research information service (CRIS: KCT0006161).
Assuntos
Disfunção Cognitiva , Spirulina , Idoso , Antioxidantes/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo , Disfunção Cognitiva/tratamento farmacológico , Método Duplo-Cego , Etanol , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
The goal of treatment for mild cognitive impairment (MCI) is to reduce the existing clinical symptoms, delay the progression of cognitive impairment and prevent the progression to Alzheimer's disease (AD). At present, there is no effective drug therapy for AD treatment. However, early intake of dietary supplements may be effective in alleviating and delaying the MCI. This study aims to evaluate the effects of sesame oil cake extract (SOCE) supplementation on cognitive function in aged 60 years or older adults with memory impairment. A total of 70 subjects received either SOCE (n = 35) or placebo (n = 35) for 12 weeks based on random 1:1 assignment to these two groups. Cognitive function was evaluated by a computerized neurocognitive function test (CNT), and changes in the concentrations of plasma amyloid ß (Aß) proteins and urine 8-OHdG (8-hydroxy-2'-deoxyguanosine) were investigated before and after the experiment. Verbal learning test index items of the CNT improved markedly in the SOCE group compared to the placebo group (p < 0.05). Furthermore, plasma amyloid-ß (1-40) and amyloid-ß (1-42) levels in the SOCE group decreased significantly compared to that in the placebo group (p < 0.05). There was no statistically significant difference in urine 8-OHdG between the two groups (p > 0.05). Collectively, intake of SOCE for 12 weeks appears to have a beneficial effect on the verbal memory abilities and plasma ß-amyloid levels of older adults with memory impairment.
Assuntos
Suplementos Nutricionais , Memória/efeitos dos fármacos , Extratos Vegetais/farmacologia , Óleo de Gergelim/farmacologia , Idoso , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/metabolismo , Cognição/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Dioxóis , Método Duplo-Cego , Ingestão de Alimentos , Feminino , Furanos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
Coffee is one of the widely sales beverage worldwide and contains numerous phytochemicals that are beneficial to health. Kahweol acetate (KA), a coffee-specific diterpene, exhibits anti-tumoric properties in human tumoric cells. However, the effect of KA on the metastasis and invasion of cancer cells and the underlying mechanisms remain unclear. The objectives of this study were to estimate the anti-tumor activity of KA and reveal the possible molecular mechanisms. KA markedly inhibited the cell proliferation enhanced by phorbol 12-myristate 13-acetate (PMA) in human fibrosarcoma cells. As well as, KA attenuated PMA-induced cell migration and invasion in a concentration-dependent manner. KA suppressed PMA-enhanced activation of matrix metalloproteinase-9 (MMP-9) through suppression of nuclear factor kappa B (NF-κB) activation. KA repressed the PMA-induced phosphorylation of Akt, c-Jun N-terminal kinase (JNK) 1/2, and p38 MAPK, which are signaling molecules upstream of MMP-9 expression. In summary, we demonstrated that the anti-tumor effects of KA might occur through the inhibition of Akt/JNK1/2/p38 MAPK phosphorylation and downregulation of NF-κB activation, leading to a decrease in MMP-9 expression. Thus, KA is a useful chemotherapeutic agent that may contribute to prevent to the metastatic tumor.
Assuntos
Café/química , Diterpenos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Acetato de Tetradecanoilforbol/toxicidade , Transcrição Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , Fibrossarcoma/patologia , Humanos , Invasividade Neoplásica/prevenção & controle , Metástase Neoplásica/prevenção & controleRESUMO
Pseudoshikonin I (PSI), a novel biomaterial isolated from Lithospermi radix, has been recognized as an herbal medicine for the treatment of infectious and inflammatory diseases. Bone remodeling maintains a balance through bone resorption (osteoclastogenesis) and bone formation (osteoblastogenesis). Bone formation is generally attributed to osteoblasts. However, the effects of PSI on the bone are not well known. In this study, we found that the ethanol extracts of PSI induced osteoblast differentiation by increasing the expression of bone morphogenic protein 4 (BMP 4). PSI positively regulates the transcriptional expression and osteogenic activity of osteoblast-specific transcription factors such as Runx2 and Osterix. To identify the signaling pathways that mediate PSI-induced osteoblastogenesis, we examined the effects of serine-threonine kinase inhibitors that are known regulators of Osterix and Runx2. PSI-induced upregulation of Osterix and Runx2 was suppressed by treatment with AKT and PKA inhibitors. These results suggest that PSI enhances osteoblast differentiation by stimulating Osterix and Runx2 via the AKT and PKA signaling pathways. Thus, the activation of Runx2 and Osterix is modulated by PSI, thereby demonstrating its potential as a treatment target for bone disease.
Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core/genética , Etanol/farmacologia , Lithospermum/química , Osteoblastos/citologia , Fator de Transcrição Sp7/genética , Animais , Proteína Morfogenética Óssea 4/metabolismo , Remodelação Óssea , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Camundongos , Naftoquinonas/química , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Extratos Vegetais/farmacologia , Fator de Transcrição Sp7/metabolismo , Transcrição Gênica/efeitos dos fármacosRESUMO
Platycodon grandiflorum has been healthy effects due to its various nutritious compounds and is considered as a functional food. Platycodon grandiflorum root-derived saponins (CKS) have been reported to show a variety of effects including anti-inflammatory and anti-oxidative activity. Although CKS have been studied on various bioactivities, the inhibitory effect of CKS on non-alcoholic steatohepatitis (NASH) is not examined. In this study, the inhibitory effects on HFD-induced NASH by CKS were determined. CKS suppressed HFD-induced hepatic lipid peroxidation level, collagen deposition, pro-fibrogenic and pro-inflammatory cytokines expression. CKS treatment suppressed HFD-induced COX-2 expression via inhibition of NF-κB p65 nuclear translocation and IκBα degradation. CKS treatment restored HFD-reduced Nrf2-mediated antioxidant enzymes expression. Furthermore, CKS treatment reinstated HFD-reduced peroxisomal proliferator-activated receptor alpha (PPARα)-regulated acyl-coA oxidase and carnitine-palmitoyl-coA transferase-1 expression. These findings suggest that CKS reduces HFD-induced NASH by up-regulation of Nrf2-mediated anti-oxidant enzymes and PPARα-regulated fatty acid oxidation.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Platycodon , Saponinas/uso terapêutico , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Relação Dose-Resposta a Droga , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Saponinas/isolamento & purificação , Saponinas/farmacologiaRESUMO
We investigated the inhibitory effects of Platycodon grandiflorum root-derived saponins (Changkil saponins: CKS) on ovalbumin-induced airway inflammation in mice. CKS suppressed leukocytes number, IgE, Th1/Th2 cytokines, and MCP-1 chemokine secretion in bronchoalveolar lavage fluid. Also, ovalbumin-increased MUC5AC, MMP-2/9, and TIMP-1/-2 mRNA expression, NF-κB activation, leukocytes recruitment, and mucus secretion were inhibited by CKS treatment. Moreover, the active component of CKS, platyconic acid A (PA), suppressed PMA-induced MUC5AC mRNA expression (from 2.1 ± 0.2 to 1.1 ± 0.1) by inhibiting NF-κB activation (from 2.3 ± 0.2 to 1.2 ± 0.1) via Akt (from 3.7 ± 0.3 to 2.1 ± 0.2) (p < 0.01) in A549 cells. Therefore, we demonstrate that CKS or PA suppressed the development of respiratory inflammation, hyperresponsiveness, and remodeling by reducing allergic responses, and they may be potential herbal drugs for allergen-induced respiratory disease prevention.
Assuntos
Anti-Inflamatórios/administração & dosagem , Pulmão/imunologia , Platycodon/química , Saponinas/administração & dosagem , Triterpenos/administração & dosagem , Animais , Linhagem Celular , Citocinas/genética , Citocinas/imunologia , Feminino , Humanos , Pulmão/efeitos dos fármacos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/imunologia , Camundongos , Camundongos Endogâmicos ICR , Mucina-5AC/genética , Mucina-5AC/imunologia , Ovalbumina/efeitos adversos , Raízes de Plantas/química , Acetato de Tetradecanoilforbol/efeitos adversos , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/imunologiaRESUMO
PURPOSE: The consequences of precipitously rising allergic skin inflammation rates worldwide have accelerated the risk of atopic dermatitis (AD). Natural product-based agents with good efficacy and low risk of side effects offer promising prevention and treatment strategies for inflammation-related diseases. We have already reported that Platycodon grandiflorum root-derived saponins (Changkil saponins, CKS) have many pharmacological effects, including anti-inflammatory and anti-allergic effects, but its influence on AD remains unclear. Therefore, we evaluated the inhibitory effect of CKS, mainly platycodin D, on AD-like skin symptoms in mice and the possible mechanisms in cells. METHODS: Mice were sensitized and challenged with 2,4-dinitrochlorobenzene (DNCB). Four weeks after challenge, mice were treated with oral administration of CKS for 4 weeks. In addition, cells were used to evaluate the effect of CKS, mainly platycodin D, on the TARC expression regulated mechanism. RESULTS: CKS attenuated DNCB-induced dermatitis severity, serum levels of IgE and TARC, and mRNA expression of TARC, TNF-α, IFN-γ, IL-4, IL-5, and IL-13 in mice. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells and mast cells in the ears. Moreover, CKS and platycodin D inhibited TNF-α/IFN-γ-induced TARC expression through the suppression of NF-κB and STAT1 and induction of Nrf2/ARE-mediated hemeoxygenase-1 (HO-1) expression in cells. CONCLUSION: We suggest that CKS and platycodin D inhibited the development of AD-like skin symptoms by regulating cytokine mediators and may be an effective alternative therapy for AD-like skin symptoms.
Assuntos
Antialérgicos/farmacologia , Dermatite Atópica/tratamento farmacológico , Extratos Vegetais/farmacologia , Platycodon/química , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Antialérgicos/química , Antialérgicos/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Dermatite Atópica/induzido quimicamente , Dinitroclorobenzeno/efeitos adversos , Regulação da Expressão Gênica , Genes Reporter , Heme Oxigenase-1/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Humanos , Imunoglobulina E/sangue , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Camundongos , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Fator de Transcrição STAT1/efeitos dos fármacos , Fator de Transcrição STAT1/metabolismo , Saponinas/química , Saponinas/isolamento & purificação , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Transforming growth factor ß (TGFß) is a multifunctional cytokine that induces growth arrest, tissue fibrosis, and epithelial-mesenchymal transition (EMT) through activation of Smad and non-Smad signaling pathways. EMT is the differentiation switch by which polarized epithelial cells differentiate into contractile and motile mesenchymal cells. Our previous studies have shown that saponins from the roots of Platycodon grandiflorum (CKS) have antiinflammatory, antioxidant, antimetastatic, and hepatoprotective effects. In this study, we investigated the inhibitory effect of CKS on TGFß1-induced alterations characteristic of EMT in human lung carcinoma A549 cells. We found that CKS-treated cells displayed inhibited TGFß1-mediated E-cadherin downregulation and Vimentin upregulation and also retained epithelial morphology. Furthermore, TGFß1-increased Snail expression, a repressor of E-cadherin and an inducer of the EMT, was reduced by CKS. CKS inhibited TGFß1-induced phosphorylation of Akt, ERK1/2, and glycogen synthase kinase-3ß (GSK-3ß). Inhibition of PI3K/Akt and ERK1/2 also blocked TGFß1-induced GSK-3ß phosphorylation and Snail activation. Furthermore, TGFß1-increased Snail expression was reduced by selective inhibitors of Akt and ERK1/2. Moreover, CKS treatment attenuated TGFß1-induced Smad2/3 phosphorylation and upregulated Smad7 expression. These results indicate that pretreatment with the CKS inhibits the TGFß1-induced EMT through PI3K/Akt, ERK1/2, GSK-3ß and Smad2/3 in human lung carcinoma cells.
Assuntos
Repressão Epigenética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Platycodon/química , Saponinas/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Regulação para Baixo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismoRESUMO
Saponins from the roots of Platycodon grandiflorum (Changkil saponins, CKS) have antioxidant and hepatoprotective properties. This study investigated the effects of CKS on AMP-activated protein kinase (AMPK) activation and hepatic lipogenesis in HepG2 cells. CKS suppressed high-glucose-induced lipid accumulation and inhibited high-glucose-induced fatty acid synthase (FAS) and sterol regulatory element binding protein-1c (SREBP-1c) expression in HepG2 cells. Moreover, the use of a pharmacological AMPK inhibitor revealed that AMPK is essential for the suppression of SREBP-1c expression in CKS-treated cells. Finally, the activation of calcium/calmodulin-dependent kinase kinase ß (CaMKKß) and SIRT1 was necessary for CKS-enhanced activation of AMPK. These results indicate that CKS prevents lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through SIRT1 and CaMKKß/AMPK activation. Using CKS to target AMPK activation may provide a promising approach for the prevention lipogenesis.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Regulação para Baixo/efeitos dos fármacos , Glucose/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/metabolismo , Extratos Vegetais/farmacologia , Platycodon/química , Saponinas/farmacologia , Sirtuína 1/genética , Proteínas Quinases Ativadas por AMP/genética , Ativação Enzimática/efeitos dos fármacos , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Sirtuína 1/metabolismo , Receptor fas/genética , Receptor fas/metabolismoRESUMO
Ginseng contains many bioactive constituents, including various ginsenosides that are believed to have anti-allergic, anti-oxidant, and immunostimulatory activities; however, its effects on atopic dermatitis (AD) remain unclear. In the current study, we hypothesized that cultivated ginseng (CG) would inhibit 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in NC/Nga mice by regulating the T helper (Th)1/Th2 balance. Also, CG inhibits TNF-α/IFN-γ-induced thymus- and activation-regulated chemokine (TARC) expression through nuclear factor-kappa B (NF-κB)-dependent signaling in HaCaT cells. CG ameliorated DNCB-induced dermatitis severity, serum levels of IgE and TARC, and mRNA expression of TARC, TNF-α, IFN-γ, IL-4, IL-5, and IL-13 in mice. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells in the ears. Furthermore, CG suppressed the TNF-α/IFN-γ-induced mRNA expression of TARC in HaCaT cells. CG inhibited TNF-α/IFN-γ-induced NF-κB activation. These results suggest that CG inhibited the development of the AD-like skin symptoms by modulating Th1 and Th2 responses in the skin lesions in mice and TARC expression by suppressing TNF-α/IFN-γ-induced NF-κB activation in keratinocytes, and so may be a useful tool in the therapy of AD-like skin symptoms.
Assuntos
Quimiocina CCL17/metabolismo , Dermatite Atópica/tratamento farmacológico , Dinitroclorobenzeno/efeitos adversos , Interferon gama/farmacologia , Panax/química , Fator de Necrose Tumoral alfa/farmacologia , Animais , Linhagem Celular , Quimiocina CCL17/sangue , Quimiocina CCL17/genética , Dermatite Atópica/etiologia , Dermatite Atópica/patologia , Humanos , Imunoglobulina E/sangue , Interleucina-13/genética , Interleucina-13/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Interleucina-5/genética , Interleucina-5/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/patologia , Masculino , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Pele/efeitos dos fármacos , Pele/patologia , Equilíbrio Th1-Th2/efeitos dos fármacosRESUMO
The purpose of this study was to investigate the anti-fibrotic effects of the aqueous extract of the Platycodi Radix root (Changkil: CK) on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. DMN treatment for 4 weeks led to marked liver fibrosis as assessed by serum biochemistry, histopathological examination, and hepatic lipid peroxidation and collagen content. CK significantly inhibited DMN-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, fibrosis score, and hepatic malondialdehyde and collagen content. CK also inhibited DMN-induced reductions in rat body and liver weights. Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited DMN-induced increases in matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-α (TNF-α) mRNA, and collagen type I and α-smooth muscle actin protein. DMN-induced cyclooxygenase-2 (COX-2) expression and nuclear factor-kappa B (NF-κB) activation was reduced by CK treatment. Furthermore, CK induced activation of nuclear erythroid 2-related factor 2 (Nrf2)-mediated antioxidant enzymes such as γ-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutathione-S-transferase (GST) in HepG2 cells. These results demonstrated that CK attenuates DMN-induced liver fibrosis through the activation of Nrf2-mediated antioxidant enzymes.
Assuntos
Antioxidantes/farmacologia , Dimetilnitrosamina/efeitos adversos , Cirrose Hepática/patologia , Extratos Vegetais/farmacologia , Actinas/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Colágeno Tipo I/metabolismo , Ciclo-Oxigenase 2/metabolismo , Glutamato-Cisteína Ligase/metabolismo , Glutationa Transferase/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Células Hep G2 , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Masculino , Malondialdeído/sangue , Metaloproteinase 13 da Matriz/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Raízes de Plantas/química , Platycodon , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
S-Allyl cysteine (SAC), a nontoxic garlic compound, has a variety of pharmacological properties, including antioxidant and hepatoprotective properties. In this report, we provide evidence that SAC prevented free fatty acid (FFA)-induced lipid accumulation and lipotoxicity in hepatocytes. SAC significantly reduced FFA-induced generation of reactive oxygen species, caspase activation and subsequent cell death. Also, SAC mitigated total cellular lipid and triglyceride accumulation in steatotic HepG2 cells. SAC significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells. Additionally, SAC down-regulated the levels of sterol regulatory element binding protein-1 (SREBP-1) and its target genes, including ACC and fatty acid synthase. Use of a specific inhibitor showed that SAC activated AMPK via calcium/calmodulin-dependent kinase kinase (CaMKK) and silent information regulator T1. Our results demonstrate that SAC activates AMPK through CaMKK and inhibits SREBP-1-mediated hepatic lipogenesis. Therefore, SAC has therapeutic potential for preventing nonalcoholic fatty liver disease.
Assuntos
Cisteína/análogos & derivados , Ácidos Graxos não Esterificados/efeitos adversos , Lipogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/genética , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Sobrevivência Celular , Cisteína/farmacologia , Regulação para Baixo , Ácidos Graxos não Esterificados/administração & dosagem , Fígado Gorduroso/prevenção & controle , Alho/química , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Hepatopatia Gordurosa não Alcoólica , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismoRESUMO
Several studies have demonstrated that the Chinese herb Gastrodia elata Blume can protect against amyloid beta-peptide (Aß)-induced cell death. To investigate the possible therapeutic effects of Gastrodia elata Blume on Alzheimer's disease, we established a rat model of Alzheimer's disease by injecting Aß25-35 into bilateral hippocampi. These rats were intragastrically administered 500 or 1 000 mg/kg Gastrodia elata Blume per day for 52 consecutive days. Morris water maze tests showed that Gastrodia elata Blume treatment significantly improved the spatial memory of Alzheimer's disease rats. Congo red staining revealed that Gastrodia elata Blume significantly reduced the number of amyloid deposits in the hippocampus of these rats. Western blot analysis showed that choline acetyltransferase expression in the medial septum and hippocampus was significantly increased by the treatment of Gastrodia elata Blume, while Ellman method showed significant decrease in the activity of acetylcholinesterase in all three regions (prefrontal cortex, medial septum and hippocampus). These findings suggest that long-term administration of Gastrodia elata Blume has therapeutic potential for Alzheimer's disease.
RESUMO
The objective of this study was to investigate the occurrence of aflatoxins in herbal medicines distributed in South Korea. A total of 700 herbal medicine samples (10 samples each for 70 types of herbal medicine) were analyzed by an enzyme-linked immunosorbent assay (ELISA) for aflatoxin B(1) (AFB(1)), and levels of total aflatoxins were quantified and confirmed by liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). The levels of recovery of the methods were 84.30 to 102.68% (ELISA for AFB(1)) and 72.17 to 90.92% (LC-MS/MS for total aflatoxins). Fifty-eight (8.29%) of 700 samples were AFB(1) positive by ELISA, and 17 (2.43%) of them were finally confirmed as positive for total aflatoxins by LC-MS/MS. Total aflatoxin levels in the herbal medicines were from 4.51 to 108.42 µg/kg. Among the 17 samples, the AFB(1) content of 6 samples (11.95 to 73.27 µg/kg) and the total aflatoxin content of 10 (12.12 to 108.42 µg/kg) samples exceeded the legal limits set by the Korea Food and Drug Administration for AFB(1) (10 µg/kg) and by the European Commission for total aflatoxins (10 µg/kg), respectively. These results demonstrate the risk to consumers of herbal medicine contamination by aflatoxins and encourage further studies to investigate the transfer rate of mycotoxins to decoction, which is the final product for consumption.
Assuntos
Aflatoxinas/isolamento & purificação , Contaminação de Alimentos/análise , Plantas Medicinais/química , Cromatografia Líquida , Qualidade de Produtos para o Consumidor , Contaminação de Medicamentos , Ensaio de Imunoadsorção Enzimática , Humanos , República da Coreia , Espectrometria de Massas em TandemRESUMO
Cultivated ginseng (CG) (Panax ginseng C.A. Meyer), an herb used in Korean herbal medicine, has been widely used in China and Japan to treat fatigue and to enhance resistance to many diseases. It contains many bioactive constituents, including various ginsenosides that are believed to have antioxidant, immunostimulatory, and antiaging activities. Previous studies have revealed that treatment with Panax ginseng is significantly associated with reduced photoaging, but the underlying mode of action has not been elucidated. In this study, we hypothesized that CG inhibits ultraviolet B (UVB)-induced collagenase activation through mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB)/activator protein-1 (AP-1)-dependent signaling in human skin fibroblasts. HS68 cells were treated with CG, followed by irradiation with UVB. Those effects were assessed by semiquantitative polymerase chain reaction, Western blotting, and enzymic activity assays. We found that CG increased cell viability and inhibited the production of reactive oxygen species in HS68 cells exposed to UVB irradiation. Pretreatment of HS68 cells with CG inhibited UVB-induced production of matrix metalloproteinase (MMP) 1 and MMP-13. Western blot analysis further revealed that CG markedly suppressed the enhancement of collagen degradation in UVB-exposed HS68 cells. Cultivated ginseng also suppressed UVB-induced activation of NF-κB, c-Jun, and c-Fos and the phosphorylation of MAPKs, which are upstream modulators of NF-κB and AP-1. These results indicate that CG inhibits UVB-induced collagenolytic MMP production by interfering with MAPK/AP-1 and NF-κB signaling and thus may be useful in the prevention and treatment of skin photoaging.
Assuntos
Fibroblastos/efeitos dos fármacos , Inibidores de Metaloproteinases de Matriz , Panax/química , Extratos Vegetais/farmacologia , Transdução de Sinais , Pele/efeitos dos fármacos , Raios Ultravioleta , Western Blotting , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , China , Colagenases/metabolismo , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Japão , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Pele/citologia , Pele/metabolismo , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos dos fármacos , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismoRESUMO
Atopic dermatitis (AD) is a chronic, relapsing, and inflammatory skin disease associated with eczematous symptoms and IgE hyperproduction. Psidium guajava is an important food crop and medicinal plant with anti-oxidant, anti-inflammatory, and anti-allergic activities, supporting its traditional uses. Our previous studies have shown that P. guajava extract inhibits Th2 chemokine expression by suppressing the activation of NF-κB and STAT1 co-stimulated with TNF-α and INF-γ. In this study, we investigated the inhibitory effect of P. guajava water extract (PGW) on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in NC/Nga mice. Treatment of cream containing PGW onto DNCB-induced AD-like skin lesions in NC/Nga mice ameliorated lesion intensity scores, levels of IgE, thymus and activation-regulated chemokine (TARC), TNF-α, and IL-4 in serum and ears. In contrast, PGW increased level of the immunosuppressive cytokine IL-10. Histological analyses demonstrated decreased thickening of the epidermis/dermis as well as dermal infiltration by inflammatory cells. These results suggest that cream containing PGW may be a potential therapeutic modality for AD and adjunctive agent to control pruritus in AD.
Assuntos
Dermatite Atópica/induzido quimicamente , Dinitroclorobenzeno/toxicidade , Extratos Vegetais/farmacologia , Psidium/química , Animais , Sequência de Bases , Citocinas/metabolismo , Primers do DNA , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Imunoglobulina E/metabolismo , Masculino , Camundongos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Água/químicaRESUMO
Platycodi Radix has been used to treat chronic diseases, such as bronchitis, asthma, and hyperlipidemia. In this study, we examined the effect of an aqueous extract, Changkil (CK), from the root of Platycodi Radix on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions. Administration of CK onto DNCB-induced AD-like skin lesions in NC/Nga mice ameliorated lesion intensity scores, levels of IgE, thymus and activation-regulated chemokine (TARC), TNF-α, and IL-4 in serum and ears. In contrast, CK increased level of the immunosuppressive cytokine IL-10. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells in the ears. CK also suppressed TNF-α/IFN-γ-induced mRNA expression and production of TARC in HaCaT cells. CK exerts beneficial effects on AD symptoms, suggesting that CK is an effective potential therapeutic agent for AD.