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In this study, we examined physiological functions as a key material to develop cosmeceuticals using extracts of Lagerstroemia macrocarpa Wall. Ex Kurz (L. macrocarpa). Initially, the L. macrocarpa extract was treated by different concentration and antioxidant assay (DPPH and ABTS) were performed to measure free radical scavenging ability. In the cytotoxicity experiment, the extract was treated into human epidermal keratinocytes with different concentrations to measure cytotoxicity. We found that the extract induces differentiation markers such as keratin (KRT)1, KRT2, KRT9, KRT10 in keratinocytes. Furthermore, the extract significantly induces involucrin (IVL), loricrin (LOR), claudin1 (CLDN1), and filaggrin (FLG) expression, suggesting that it may enhance skin barrier functions. Especially, the extract restored FLG expression inhibited by interleukin (IL)-4/IL-13 in in vitro atopic dermatitis-like model. Therefore, we expect L. macrocarpa extract will be an effective material to develop the therapeutic and cosmeceutical of atopic dermatitis.
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Dermatite Atópica , Lagerstroemia , Humanos , Lagerstroemia/metabolismo , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/metabolismo , Proteínas de Filamentos Intermediários/metabolismo , Proteínas de Filamentos Intermediários/farmacologia , Proteínas de Filamentos Intermediários/uso terapêutico , Estrutura Molecular , Queratinócitos , Extratos Vegetais/metabolismo , Transdução de Sinais , Fator de Transcrição STAT6/metabolismo , Fator de Transcrição STAT6/farmacologiaRESUMO
Objective: The hypothalamus regulates energy homeostasis, and its damage results in severe obesity. We aimed to investigate the multifaceted characteristics of hypothalamic obesity. Methods: We performed multidimensional analyses of brain structure/function and psychological and behavioral phenotypes in 29 patients with hypothalamic damage (HD) (craniopharyngioma) and 31 controls (non-functional pituitary adenoma). Patients underwent structural and functional magnetic resonance imaging and completed self-reports and cognitive tasks. Results: Patients with HD showed significantly higher postoperative weight gain than controls. The HD group also showed significant hypothalamic damage and lower neural activation in the left caudate nucleus in response to food images. The HD group had significantly higher food inattention, lower satiety, and higher restrained eating behavior. Within the HD group, higher restrained eating behavior was significantly associated with lower activation in the bilateral fusiform gyrus. Conclusion: These results suggest that hypothalamic damage contributes to weight gain by altering the brain response, attention, satiety, and eating behaviors. The present study proposes novel neuro-psycho-behavioral mechanisms targeted for patients with hypothalamic obesity.
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Doenças Hipotalâmicas , Hipotálamo , Humanos , Hipotálamo/patologia , Obesidade/complicações , Obesidade/diagnóstico por imagem , Obesidade/patologia , Neuroimagem , Doenças Hipotalâmicas/patologia , Aumento de Peso , Estudos de Coortes , CogniçãoRESUMO
BACKGROUND: Although recent studies comparing various dosages and intervals of vitamin D supplementation have been published, it is yet to be elucidated whether there is an appropriate dose or interval to provide benefit regarding fracture risk. We aimed to assess the published evidence available to date regarding the putative beneficial effects of vitamin D supplements on fractures and falls according to various dosages and intervals. METHODS: We performed a meta-analysis of randomized controlled studies reporting associations between vitamin D supplementation and the risks of fractures and falls in PubMed, EMBASE, and Cochrane library. Studies with supplements of ergocalciferol or calcitriol, those with a number of event ≤10, or those with a follow-up duration of less than 6 months were also excluded. RESULTS: Thirty-two studies were included in the final analysis. Vitamin D supplementation with daily dose of 800 to 1,000 mg was associated with lower risks of osteoporotic fracture and fall (pooled relative risk [RR], 0.87; 95% confidence interval [CI], 0.78 to 0.97 and RR, 0.91; 95% CI, 0.85 to 0.98), while studies with <800 or >1,000 mg/day did not. Also, among intervals, daily administration of vitamin D was associated with the reduced risk of falls, while intermittent dose was not. Also, patients with vitamin D deficiency showed a significant risk reduction of falls after vitamin D supplementation. CONCLUSION: Daily vitamin D dose of 800 to 1,000 IU was the most probable way to reduce the fracture and fall risk. Further studies designed with various regimens and targeted vitamin D levels are required to elucidate the benefits of vitamin D supplements.
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Fraturas por Osteoporose , Deficiência de Vitamina D , Acidentes por Quedas/prevenção & controle , Suplementos Nutricionais , Humanos , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Vitamina DRESUMO
Kurarinone (KR), a naturally occurring flavonoid in Sophora flavescens Aiton and a traditional herbal medicine, reportedly has anti-cancer activity against various cancer types both in vitro and in vivo. However, the cellular mechanism of KR remains unknown. Therefore, we aimed to elucidate the mechanism of cell cycle arrest induced by KR in human colorectal cancer cells. KR not only reduced cell proliferation but also induced G0/G1 arrest of colorectal cancer cell lines. The results of western blotting analysis showed that KR reduced the protein levels of cyclin D1/D3 and CDK4/6 by downregulating signaling proteins such as K-RAS, c-MYC, and p-extracellular signal-regulated kinase. Additionally, KR arrested the cell cycle in the G0/G1 phase in a p53-independent manner, and decreased the protein level of K-RAS by proteasomal degradation dependent on WDR76, an E3 ubiquitin ligase. From these results, we propose that KR could be a potent anti-cancer agent, acting through the degradation of K-RAS dependent on WDR76, regardless of the p53 status.
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Proteínas de Ciclo Celular , Neoplasias Colorretais , Proteínas de Ligação a DNA , Flavonoides , Apoptose , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Proteínas de Ligação a DNA/metabolismo , Flavonoides/farmacologia , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Proteínas Proto-Oncogênicas p21(ras) , Proteína Supressora de Tumor p53/metabolismoRESUMO
Peucedanum japonicum Thunberg (PJT) has been used in traditional medicine to treat colds, coughs, fevers, and other inflammatory diseases. The goal of this study was to investigate whether 3'-isovaleryl-4'-senecioylkhellactone (IVSK) from PJT has anti-inflammatory effects on lung epithelial cells. The anti-inflammatory effects of IVSK were evaluated using phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells and regular human lung epithelial cells as a reference. IVSK reduced the secretion of the inflammatory mediators interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1), and the mRNA expression of IL-6, IL-8, MCP-1, and IL-1ß. Additionally, it inhibited the phosphorylation of IκB kinase (IKK), p65, Iκ-Bα, and mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK in A549 cells stimulated with PMA. Moreover, the binding affinity of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) was significantly reduced in the luciferase assay, while nuclear translocation was markedly inhibited by IVSK in the immunocytochemistry. These findings indicate that IVSK can protect against inflammation through the AP-1 and NF-κB pathway and could possibly be used as a lead compound for the treatment of inflammatory lung diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Apiaceae/metabolismo , Células Epiteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Ésteres de Forbol/farmacologia , Células A549/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Quinase I-kappa B/metabolismo , Inflamação , Mediadores da Inflamação/metabolismo , Interleucina-1beta , Interleucina-8 , Proteínas Quinases Ativadas por Mitógeno/metabolismo , RNA Mensageiro/metabolismo , Fator de Transcrição AP-1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The study aimed to examine the effects of self-acupunctural hand massage using aromatic oil on the stress, fatigue, and vital signs of Korean middle-aged women. A quasi-experimental study using a pretest/posttest control group, nonsynchronized design was employed. The study participants consisted of 55 middle-aged women (27 in the experiment group and 28 in the control group), who visited a community center in Seoul, South Korea. Self-acupunctural hand massage using aromatic oil as an experimental intervention was performed once per day, 6 minutes per session for the left and right hands each, for 3 weeks. A questionnaire was designed to measure the general characteristics, stress, fatigue, and vital signs (blood pressure and pulse rate). There were significant differences in the degrees of stress, fatigue, and vital signs (blood pressure) between the 2 groups. Self-acupunctural hand massage using aromatic oil decreased the stress, fatigue, and vital signs (blood pressure) of Korean middle-aged women. Self-acupunctural hand massage using aromatic oil can be utilized as an effective nursing intervention for decreasing stress, fatigue, and vital signs (blood pressure) for middle-aged women in clinical practice.
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Fadiga , Massagem , Pressão Sanguínea/fisiologia , Fadiga/terapia , Feminino , Frequência Cardíaca , Humanos , Pessoa de Meia-Idade , Sinais VitaisRESUMO
Pyrus pyrifolia Nakai (P. pyrifolia) has been traditionally used in East Asia to treat diseases such as phlegm, cough, hangover, and fever. However, there is no investigation that evaluates the biological activities of the leaves of P. pyrifolia. This study aims at describing the anti-inflammatory effects of PP, a bioactive fraction from the leaves of P. pyrifolia, in lipopolysaccharide (LPS)-stimulated THP-1 cells. Initially, PP decreased the protein and RNA expression of TNF-α, MCP-1, IL-8, and IL-6 induced by LPS. Moreover, PP attenuated the phosphorylation of p38, JNK, and ERK. In addition, after stimulation with LPS, the degradation of IκB-α was suppressed by PP, and the phosphorylation of IκB-α and p65 was suppressed by PP. Additionally, PP increased HO-1, which controls the production of inflammatory molecules, by activating Nrf2. These results indicated that PP could be used as an anti-inflammatory drug to promote wellness.
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Among 276 herbal extracts, a methanol extract of Castanopsis cuspidata var. sieboldii stems was selected as an experimental source for novel acetylcholinesterase (AChE) inhibitors. Five compounds were isolated from the extract by activity-guided screening, and their inhibitory activities against butyrylcholinesterase (BChE), monoamine oxidases (MAOs), and ß-site amyloid precursor protein cleaving enzyme 1 (BACE-1) were also evaluated. Of these compounds, 4'-O-(α-L-rhamnopyranosyl)-3,3',4-tri-O-methylellagic acid (3) and 3,3',4-tri-O-methylellagic acid (4) effectively inhibited AChE with IC50 values of 10.1 and 10.7 µM, respectively. Ellagic acid (5) inhibited AChE (IC50 = 41.7 µM) less than 3 and 4. In addition, 3 effectively inhibited MAO-B (IC50 = 7.27 µM) followed by 5 (IC50 = 9.21 µM). All five compounds weakly inhibited BChE and BACE-1. Compounds 3, 4, and 5 reversibly and competitively inhibited AChE, and were slightly or non-toxic to MDCK cells. The binding energies of 3 and 4 (- 8.5 and - 9.2 kcal/mol, respectively) for AChE were greater than that of 5 (- 8.3 kcal/mol), and 3 and 4 formed a hydrogen bond with Tyr124 in AChE. These results suggest 3 is a dual-targeting inhibitor of AChE and MAO-B, and that these compounds should be viewed as potential therapeutics for the treatment of Alzheimer's disease.
Assuntos
Inibidores da Colinesterase/farmacologia , Ácido Elágico/isolamento & purificação , Ácido Elágico/farmacologia , Fagaceae/química , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Animais , Bioensaio , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fracionamento Químico , Inibidores da Colinesterase/farmacocinética , Diálise , Cães , Electrophorus , Ácido Elágico/farmacocinética , Células HL-60 , Humanos , Ligação de Hidrogênio , Cinética , Células Madin Darby de Rim Canino , Metanol , Simulação de Acoplamento Molecular , Inibidores da Monoaminoxidase/farmacocinética , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/químicaRESUMO
The trabecular bone score (TBS) was introduced as an indirect index of trabecular microarchitecture, complementary to bone mineral density (BMD), and is derived using the same dual energy X-ray absorptiometry images. Recently, it has been approved for clinical use in Korea. Therefore, we conducted a comprehensive review to optimize the use of TBS in clinical practice. The TBS is an independent predictor of osteoporotic fractures in postmenopausal women and men aged >50 years. The TBS is potentially useful in monitoring the skeletal effects of anabolic agents but not of antiresorptive agents. In postmenopausal women with type 2 diabetes mellitus, the TBS assesses osteoporotic fracture risk not captured by BMD. However, high body mass index and soft tissue thickness can cause underestimation of the TBS; however, this limitation has been improved in recent versions of the TBS software. However, a high precision error and low reproducibility limit the use of TBS. This review may provide information on the application of the TBS in clinical practice based on reliable evidence.
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Objective: Several attempts have been done to capture damaged hypothalamus (HT) using volumetric measurements to predict the development of hypothalamic obesity in patients with craniopharyngioma (CP). This study was to develop a novel method of HT volume measurement and examine the associations between postoperative HT volume and clinical parameters in patients with CP. Methods: We included 78 patients with adult-onset CP who underwent surgical resection. Postoperative HT volume was measured using T1- and T2-weighted magnetic resonance imaging (MRI) with a slice thickness of 3 mm, and corrected for temporal lobe volume. We collected data on pre- and postoperative body weights, which were measured at the time of HT volume measurements. Results: The corrected postoperative HT volume measured using T1- and T2-weighted images was significantly correlated (r=0.51 [95% confidence interval (CI) 0.32 to 0.67], P<0.01). However, HT volume was overestimated using T1-weighted images owing to obscured MR signal of the thalamus in patients with severe HT damage. Therefore, we used T2-weighted images to evaluate its clinical implications in 72 patients with available medical data. Postoperative HT volume was negatively associated with preoperative body weight and preoperative tumor volume (r=-0.25 [95% CI -0.45 to -0.04], P=0.04 and r=-0.26 [95% CI -0.40 to -0.15], P=0.03, respectively). In the subgroup analysis of CP patients who underwent primary surgery (n=56), pre- and postoperative body weights were negatively associated with HT volume (r=-0.30 [95% CI -0.53 to -0.03], P=0.03 and r=-0.29 [95% CI -0.53 to -0.02], P=0.03, respectively). Conclusions: Adult-onset CP patients showed negative associations between postoperative HT volume and preoperative/postoperative body weight using a new method of HT volume measurement based on T2-weighted images.
Assuntos
Craniofaringioma/diagnóstico por imagem , Craniofaringioma/cirurgia , Hipotálamo/diagnóstico por imagem , Hipotálamo/cirurgia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
This study aimed to determine the combined treatment effects of Mulligan sustained natural apophyseal glides (SNAGs) and low-level laser therapy (LLLT) on function, pain, and range of motion (ROM) in patients with chronic low back pain. A total of 49 adults participated in this study and were randomly divided into three groups (SNAGs with LLLT group, SNAGs group, and control group). The participants in the SNAGs with LLLT group received SNAGs for 10 min, LLLT for 10 min, and electrotherapy for 10 min. The SNAGs group received SNAGs for 10 min and electrotherapy for 20 min. The control group received electrotherapy for 30 min. All participants received the assigned treatment for 30 min a day, 3 times a week, for 4 weeks. We used the visual analogue scale (VAS) to measure pain, the modified-modified Schober test (MMST) to measure ROM, and the Roland Morris disability questionnaire (RMDQ) to measure physical disability. Compared to the pre-intervention values, the VAS and MMST scores significantly increased after the intervention in the SNAGs with LLLT group (p = 0.000) and the SNAGs group (p = 0.000). The RMDQ score significantly improved in the SNAGs with LLLT (p = 0.000), SNAGs (p = 0.000) and control (p = 0.025) group after the intervention. The inter-group differences were greater for the SNAGs with LLLT and SNAGs groups than for the control group (p = 0.001), and the difference was greater for the SNAGs with LLLT than for the SNAGs (p = 0.001) with respect to the VAS, MMST, and RMDQ scores. These results indicate that significant improvement in pain, function, and ROM may be achieved by a combination of SNAGs and LLLT to treat chronic low back pain.
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Until now, magnetic hyperthermia was used to remove solid tumors by targeting magnetic nanoparticles (MNPs) to tumor sites. In this study, leukemia cells in the bloodstream were directly removed by whole-body hyperthermia, using leukemia cell-specific MNPs. An epithelial cellular adhesion molecule (EpCAM) antibody was immobilized on the surface of MNPs (EpCAM-MNPs) to introduce the specificity of MNPs to leukemia cells. The viability of THP1 cells (human monocytic leukemia cells) was decreased to 40.8% of that in control samples by hyperthermia using EpCAM-MNPs. In AKR mice, an animal model of lymphoblastic leukemia, the number of leukemia cells was measured following the intravenous injection of EpCAM-MNPs and subsequent whole-body hyperthermia treatment. The result showed that the leukemia cell number was also decreased to 43.8% of that without the treatment of hyperthermia, determined by Leishman staining of leukemia cells. To support the results, simulation analysis of heat transfer from MNPs to leukemia cells was performed using COMSOL Multiphysics simulation software. The surface temperature of leukemia cells adhered to EpCAM-MNPs was predicted to be increased to 82 °C, whereas the temperature of free cells without adhered MNPs was predicted to be 38 °C. Taken together, leukemia cells were selectively removed by magnetic hyperthermia from the bloodstream, because EpCAM-modified magnetic particles were specifically attached to leukemia cell surfaces. This approach has the potential to remove metastatic cancer cells, and pathogenic bacteria and viruses floating in the bloodstream.
Assuntos
Hipertermia Induzida/métodos , Nanopartículas de Magnetita/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Animais , Anticorpos Imobilizados/administração & dosagem , Anticorpos Imobilizados/química , Linhagem Celular , Sobrevivência Celular , Modelos Animais de Doenças , Molécula de Adesão da Célula Epitelial/imunologia , Molécula de Adesão da Célula Epitelial/metabolismo , Humanos , Separação Imunomagnética , Nanopartículas de Magnetita/química , Camundongos , Camundongos Endogâmicos AKR , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismoRESUMO
Aim: To mitigate the side effects of medical treatment by Prussian blue (PB), a well-known adsorbent for radioactive cesium (Cs), PB-deposited magnetic nanoparticles (MNPs), were prepared and analyzed on the adsorbent capacity for Cs removal. Materials & methods: The PB-deposited MNPs were prepared by photo-deposition method and investigated for their Cs adsorption properties in vitro and in vivo. The distribution of the adsorbents was also evaluated in C57BL/6 mice. Results: PB-deposited MNPs provided an improved adsorbent capacity for Cs removal and reduced toxicity to blood cells compared with those of bulk PB. Conclusion: PB-deposited MNPs could be considered as an alternative of PB-based medicine to reduce the possible hazards caused by high dose of PB intake.
Assuntos
Radioisótopos de Césio/química , Compostos Férricos/química , Nanopartículas Metálicas/química , Reação do Azul da Prússia/métodos , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espectroscopia FotoeletrônicaRESUMO
Among the most critical needs of natural product chemistry is a complete library of pure reference substances. Some khellactone-type isomers of pharmacological importance are either still lacking reference substances or references are only available in limited amounts. To address this need, a recycling high-performance liquid chromatography (R-HPLC) strategy was adopted to improve the isomer separation efficiency from Peucedanum japonicum. Under the optimal isolation conditions, we obtained isomerically pure substances, particularly khellactone coumarins with different substituent groups. Isolated compounds attained purities greater than 98% as determined by ultra-performance liquid chromatography-charged aerosol detector (UPLC-CAD) and photodiode array (PDA). The structures of these compounds were identified according to their mass patterns and 2D NMR spectra. The proposed methods of single-column recycling obtained the same amount of product as conventional systems while being simple, increasing efficiency and reducing cost.
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Apiaceae/química , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/normas , Cumarínicos/análise , Cumarínicos/química , Camundongos , Extratos Vegetais/normas , Extratos Vegetais/toxicidade , Raízes de Plantas/química , Células RAW 264.7RESUMO
Cedrela odorata L. is a native plant of the Amazon region. The bark is used in folk remedies for the treatment of diarrhea, vomiting, fever and inflammation. Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease accompanied by itching. It is a complex disease involving environmental factors and genetic factors. In the present study, the anti-inflammatory and anti-allergic effects of C. odorata L. methanol extract (COEE) on tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated HaCaT keratinocyte cells were investigated. ELISA and RT-PCR analysis revealed that the extract had anti-inflammatory effects, and reduced the interleukin (IL)-6 and IL-8 levels of the HaCaT cells. In addition, COEE exhibited anti-allergic effects, comprising a reduction in the thymus and activation-regulated chemokine and macrophage-derived chemokine levels. In addition, pathway analysis and comparison with Bay11-7082 indicated that these effects are due to the inhibition of nuclear factor (NF)-κB in TNF-α/IFN-γ-induced HaCaT cells. Therefore, the results of the present study suggest that COEE has anti-inflammatory and anti-allergic properties in TNF-α and IFN-γ-stimulated HaCaT cells, which are associated with the inhibition of pro-inflammatory cytokines and chemokines via the NF-κB pathway.
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Oxidative stress, which is induced by reactive oxygen species (ROS), causes cellular damage which contributes to the pathogenesis of neurodegenerative diseases. Momordica charantia (MC), a traditional medicinal plant, is known to have a variety of health benefits, such as antidiabetic, anti-inflammatory, and antioxidant effects. However, it is unknown whether MC has protective effects against oxidative stress-induced neuronal cell death. The aim of this study was to investigate the potential action of MC on oxidative stress induced by H2O2. First, we tested whether the pretreatment of Momordica charantia ethanol extract (MCEE) attenuates H2O2-induced cell death in human neuroblastoma SK-N-MC cells. MCEE pretreatment significantly improved cell viability and apoptosis that deteriorated by H2O2. Further, MCEE ameliorated the imbalance between intracellular ROS production and removal through the enhancement of the intracellular antioxidant system. Intriguingly, the inhibition of apoptosis was followed by the blockage of mitochondria-dependent cell death cascades and suppression of the phosphorylation of the mitogen-activated protein kinase signaling (MAPKs) pathway by MCEE. Taken together, MCEE was shown to be effective in protecting against H2O2-induced cell death through its antioxidant and anti-apoptotic properties.
Assuntos
Antioxidantes/farmacologia , Morte Celular/efeitos dos fármacos , Momordica charantia , Neuroblastoma/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Peróxido de Hidrogênio , Mitocôndrias/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fitoterapia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Rhododendron album Blume (RA) has traditionally been used as an herbal medicine and is considered to have antiinflammatory properties. It is a wellknown medicine for treatment of allergic or atopic diseases. In the present study, the biological effects of an RA methanol extract (RAME) on inflammation were investigated in tumor necrosis factorα (TNFα)/interferonγ (IFNγ)stimulated human keratinocytes. The present study aimed to investigate the potential mechanisms by which RAME inhibited TNFα/IFNγinduced expression of chemokines [thymus and activation-regulated chemokine (TARC) and macrophagederived chemokine (MDC)] and cytokines [interleukin (IL)6 and IL8] through the nuclear factorκB (NFκB) pathway in human keratinocytes. The effects of RAME treatment on cell viability were investigated in TNFα/IFNγstimulated HaCaT cells. The expression of TARC, MDC, IL6 and IL8 was assessed using reverse transcriptionquantitative polymerase chain reaction analysis or ELISA, and its effect on the inhibitory mitogen-activated protein kinase pathway was also studied using western blot analysis. TNFα/IFNγ induced the expression of IL6, IL8, TARC and MDC in a dosedependent manner through NFκB and Janus kinase/signal transducers and activators of transcription (JAK/STAT) activation. Notably, treatment with RAME significantly suppressed TNF-α/IFN-γ-induced expression of IL6, IL8, TARC, and MDC. In addition, RAME treatment inhibited the activation of NFκB and the JAK/STAT pathway in TNFα/IFNγinduced HaCaT cells. These results suggest that RAME decreases the production of chemokines and proinflammatory cytokines by suppressing the NFκB and the JAK/STAT pathways. Consequently, RAME may potentially be used for treatment of atopic dermatitis.
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Interferon gama/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Rhododendron/química , Fatores de Transcrição STAT/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Eletroforese em Gel de Poliacrilamida , Humanos , Imuno-Histoquímica , Extratos Vegetais/químicaRESUMO
Acupuncture originated within the auspices of Oriental medicine, and today is used as an alternative method for treating various diseases and symptoms. The physiological mechanisms of acupuncture appear to involve the release of endogenous opiates and neurotransmitters, with the signals mediating through electrical stimulation of the central nervous system (CNS). Earlier we reported a nanoporous stainless steel acupuncture needle with enhanced therapeutic properties, evaluated by electrophysiological and behavioral responses in Sprague-Dawley (SD) rats. Herein, we investigate molecular changes in colorectal cancer (CRC) rats by acupuncture treatment using the nanoporous needles. Treatment at acupoint HT7 is found most effective at reducing average tumor size, ß-catenin expression levels, and the number of aberrant crypt foci in the colon endothelium. Surface modification of acupuncture needles further enhances the therapeutic effects of acupuncture treatment in CRC rats.
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Terapia por Acupuntura , Neoplasias Colorretais/terapia , Nanoporos , Agulhas , Pontos de Acupuntura , Animais , Pólipos do Colo/patologia , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Masculino , Nanoporos/ultraestrutura , Estadiamento de Neoplasias , Ratos Sprague-Dawley , Propriedades de Superfície , Carga Tumoral , beta Catenina/metabolismoRESUMO
Neem (Azadirachta indica A. Juss.) leaf has been reported to exert anti-inflammatory, antibacterial and antioxidant effects. The purpose of this study was to investigate the protective effects of neem leaf extract (NLE) against cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced pulmonary inflammation. Treatment with NLE significantly attenuated the infiltration of inflammatory cells, such as neutrophils and macrophages in bronchoalveolar lavage fluid (BALF). NLE also reduced the production of reactive oxygen species and the activity of neutrophil elastase in BALF. Moreover, NLE attenuated the release of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in BALF. NLE inhibited the recruitment of inflammatory cells and the expression of monocyte chemoattractant protein-1 (MCP-1) in the lungs of mice with CS- and LPS-induced pulmonary inflammation. NLE also decreased the expression of inducible nitric oxide synthase (iNOS) in the lungs of the mice CS- and LPS-induced pulmonary inflammation. Furthermore, treatment with NLE significantly attenuated the activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in the lungs mice exposed to CS and LPS. NLE also inhibited the phosphorylation of nuclear factor (NF)-κB and inhibitor of NF-κB (IκB) in the lungs of mice expose to CS and LPS. These findings thus suggest that NLE has potential for use in the treatment of chronic obstructive pulmonary disease.
Assuntos
Azadirachta/química , Extratos Vegetais/administração & dosagem , Pneumonia/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Líquido da Lavagem Broncoalveolar/química , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/genética , Lipopolissacarídeos/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , Extratos Vegetais/química , Folhas de Planta/química , Pneumonia/induzido quimicamente , Pneumonia/genética , Pneumonia/patologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/patologia , Espécies Reativas de Oxigênio/metabolismo , Fumar/efeitos adversos , Fator de Necrose Tumoral alfa/genéticaRESUMO
Physalis peruviana L. (PP) is a medicinal herb that has been confirmed to have several biological activities, including anticancer, antioxidant and anti-inflammatory properties. The aim of the present study was to evaluate the protective effect of PP on cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced pulmonary inflammation. Treatment with PP significantly reduced the influx of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and lung of mice with CS- and LPS-induced pulmonary inflammation. PP also decreased the levels of reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF. PP effectively attenuated the expression of monocyte chemoattractant protein-1 (MCP-1) and the activation of extracellular signal-regulated kinase (ERK) in the lung. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) activation and heme oxygenase-1 (HO-1) expression were increased by PP treatment. In an in vitro experiment, PP reduced the mRNA expression of TNF-α and MCP-1, and the activation of ERK in CS extract-stimulated A549 epithelial cells. Furthermore, PP increased the activation of Nrf2 and the expression of HO-1 in A549 cells. These findings suggest that PP has a therapeutic potential for the treatment of pulmonary inflammatory diseases, such as chronic obstructive pulmonary disease.