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Purple rice, locally known as "Cam" rice, is cultivated in the southern region of Vietnam. The bran of "Cam" rice is often disregarded and underutilized; nevertheless, it harbours substantial nutritive value, particularly in terms of antioxidant compounds. Additionally, sonication, an emerging and "green" technological approach, has been employed to augment the extraction efficiency of these antioxidants. This research is aimed at optimizing and maximizing the antioxidant recovery capacity including phenolic and total flavonoid compounds, along with their antioxidant activities, through the assistance of ultrasound waves. The effect of the extract on the starch digestion process was also investigated. The study employed the Box-Behnken experimental design, encompassing three variables: extraction time (20-40 minutes), temperature (60-80°C), and solvent-to-material ratio (8 : 1 to 12 : 1). Analysis was conducted on total phenolic compounds, total flavonoid content, and antioxidant activities. Results demonstrated that the peak yield of antioxidant compounds and their corresponding activities were attained at an extraction duration of 29.38 minutes, a temperature of 69°C, and a solvent-to-material ratio of 9.92. Under these optimal conditions, the yields were as follows: total phenolic compounds at 60.821 mg GAE/g, total flavonoid compounds at 3.2696 mg QE/g, percentage inhibition of DPPH at 74.778%, and FRAP value at 54.112 µmol Fe (II)/g. The established models were validated and exhibited a strong alignment between predicted and actual values, with disparities of less than 3% under optimal conditions. Furthermore, the extract was codigested with cooked corn starch, revealing a dose-dependent effect on starch digestibility. The sluggishness of digestion rate was observed when 20 mg of the extract was supplemented to 200 mg of cooked corn starch. This suggests that rice bran extract holds promise as an effective ingredient for mitigating starch digestion, particularly beneficial for individuals dealing with diabetes.
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The discovery of insulin in 1921 introduced a new branch of research into insulin activity and insulin resistance. Many discoveries in this field have been applied to diagnosing and treating diseases related to insulin resistance. In this mini-review, the authors attempt to synthesize the updated discoveries to unravel the related mechanisms and inform the development of novel applications. Firstly, we depict the insulin signaling pathway to explain the physiology of insulin action starting at the receptor sites of insulin and downstream the signaling of the insulin signaling pathway. Based on this, the next part will analyze the mechanisms of insulin resistance with two major provenances: the defects caused by receptors and the defects due to extra-receptor causes, but in this study, we focus on post-receptor causes. Finally, we discuss the recent applications including the diseases related to insulin resistance (obesity, cardiovascular disease, Alzheimer's disease, and cancer) and the potential treatment of those based on insulin resistance mechanisms.
Assuntos
Doença de Alzheimer , Resistência à Insulina , Humanos , Insulina , Transdução de Sinais , Sítios de LigaçãoRESUMO
One new neolignan (1) and one new phenolic compound (2), together with four known compounds (3-6) were isolated from the heartwood of Mansonia gagei. Their structures were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR and HRESIMS. The absolute configuration of 2 was established based on the DP4+ protocol and by comparison of experimental and calculated ECD spectra. All isolated compounds were evaluated by DPPH assay for antioxidant activity, while compounds 3-6 were assayed using the MTT-based colorimetric assay for cytotoxicity against lung cancer cell line A549. In terms of antioxidant activity, 1 and 3 exhibited stronger activity (IC50 14.91 ± 1.10 and 17.46 ± 0.16 µM, respectively) than the positive control, ascorbic acid (IC50 30.20 ± 0.47 µM). Among the compounds tested for cytotoxicity, compound 3 showed the highest activity, with an IC50 value of 26.04 ± 2.95 µM.
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Bio-guided fractionation of the 80% ethanol extract of the aerial parts of Elsholtzia penduliflora W. W. Smith (Lamiaceae) led to the isolation of seven new triterpene glycosides, i.e., pendulosides A-G (1-7), and one known compound (8). Their structures were determined based on extensive spectroscopic analysis, including one- and two-dimensional nuclear magnetic resonance spectroscopy, high-resolution electrospray ionization mass spectroscopy, and the results of hydrolytic cleavage. Compounds 1, 3-5, and 7-8 were tested for cytotoxic activity against two human cancer cell lines in vitro using the MTT assay method. Among them, two compounds (3 and 7) displayed significant cytotoxicities against human lung cancer (A549) cells with IC50 values of 9.01 ± 1.52 µM and 6.18 ± 1.06 µM, respectively, and human breast cancer (MCF-7) cells with IC50 values of 10.98 ± 1.76 µM and 6.82 ± 1.09 µM, respectively. The results suggest that compounds 3 and 7 might be useful for the therapeutic study of cancer.
Assuntos
Antineoplásicos Fitogênicos , Antineoplásicos , Lamiaceae , Triterpenos , Antineoplásicos/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Etanol , Glicosídeos/química , Glicosídeos/farmacologia , Humanos , Estrutura Molecular , Componentes Aéreos da Planta , Extratos Vegetais/farmacologia , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Background: Second-hand smoking (SHS) is associated with many health problems. However, its prevalence in the community population aged 15 years and older in Vietnam is unknown. Objectives: To quantify the prevalence of SHS in Vietnamese communities aged 15 and above. Methods: This is a meta-analysis that reviewed studies of the prevalence of SHS in Vietnam published in MEDLINE, Scopus, Pubmed and the WHO library database between 1 January 2010 and 31 December 2019. MedCalc was used to perform all the analyses, and publication bias was determined using funnel plots and Egger regression asymmetry tests. Q-test and I2 statistic were used to identify heterogeneity across studies. Results: There were 7 articles that met our inclusion criteria 2 surveys at the national level, 3 Cross-sectional studies and 2 Case-control studies) involving 184 921 participants. According to the meta-analysis, the overall random-effects pooled prevalence of SHS was 54.6% (95% CIs: 44.900-64.154) with a high level of heterogeneity (P = .0001, Q = 2245.60, I 2 = 99.73%). It is noteworthy that the pooled prevalence of SHS rose throughout the course of the survey years. Our research found no evidence of publication bias. Conclusions: Vietnam has ratified the implementation the WHO Framework Convention on Tobacco Control (FCTC) in 2004, there are still a large number of people who are adversely impacted by SHS. Given the tremendous cost that SHS imposes on health systems, our results underscore the critical need for the Vietnamese government to expedite an implementation of a set of stronger tobacco control practices, thus reducing the incidence of smoking-related illnesses and fatalities.
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The study aimed to evaluate the contribution of the FTO A/T polymorphism (rs9939609) to the prediction of the future type 2 diabetes (T2D). A population-based prospective study included 1443 nondiabetic subjects at baseline, and they were examined for developing T2D after 5-year follow-up. Cox proportional hazards model was used to evaluate the hazard ratio (HR) of rs9939609 to the future T2D in the models adjusted for the confounding factors including socio-economic status, lifestyle factors (smoking and drinking history, sporting habits, and leisure time), and clinical patterns (obese status, blood pressures, and dyslipidemia) at baseline. The area under receiver operating characteristic curve (AUC) was used to measure the power to predict individuals with T2D. The FTO-rs9939609 polymorphism was a significant predictor of future T2D in the model unadjusted, and it remained significant in the final model after adjustment for the confounding factors, showing an additive effect of the A-allele (HR = 1.35, 95% CI = 1.02-1.78, P = 0.036, AUC = 0.676). For normoglycemic subjects at baseline, the similar final adjusted model reported the increased HR per A-allele (HR = 1.50, 95% CI = 1.09-2.07, P = 0.012, AUC = 0.697). Five-year changes in BMI, waist circumference, and systolic blood pressure did not remove the contribution of rs9939609 to increased HR of T2D. The population attributable risk for risk genotype was 13.6%. In conclusion, the study indicates that the FTO-rs9939609 polymorphism is an important genetic predictor for future T2D in Vietnamese population.
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato , Diabetes Mellitus Tipo 2 , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Estudos ProspectivosRESUMO
We sampled nasal-pharyngeal throat swabs from 96,123 asymptomatic individuals at risk of SARS-CoV-2 infection, and generated 22,290 pools at collection, each containing samples from two to seven individuals. We detected SARS-CoV-2 in 24 pools, and confirmed the infection in 32 individuals after resampling and testing of 104 samples from positive pools. We completed the testing within 14 days. We would have required 64 days to complete the screening for the same number of individuals if we had based our testing strategy on individual testing. There was no difference in cycle threshold (Ct) values of pooled and individual samples. Thus, compared with individual sample testing, our approach did not compromise PCR sensitivity, but saved 77% of the resources. The present strategy might be applicable in settings, where there are shortages of reagents and the disease prevalence is low, but the demand for testing is high.
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COVID-19/epidemiologia , Programas de Rastreamento , SARS-CoV-2 , Teste de Ácido Nucleico para COVID-19 , Surtos de Doenças , Humanos , Nasofaringe/virologia , Manejo de Espécimes , Vietnã/epidemiologiaRESUMO
Pleuropulmonary blastoma (PPB) is a rare malignant tumor in childhood cancer. This type of tumor is difficult to identify and can easily be misdiagnosed. The International PPB protocol is a complicated and aggressive protocol. It is not easily applicable to developing countries where hospitals do not have enough resources. Here we present a challanging case of a patient successfully treated in Vietnam, using limited medical resources. The patient (22 month old, male) was diagnosed with congenital cystic adenomatoid malformation in his 1st hospital admission. After 6 months of onset, the patient was diagnosed with PPB type II in the fourth hospitalization following analysis of a lung CT scan and a pathology report. After the aggressive chemotherapy regimen, the patient had two episodes of severe neutropenia and infection from which he recovered. The patient received chemotherapy and surgery treatment at our hospital, but received radiation under general anesthesia and rehabilitation therapy to improve respiration at another hospital over 600 km away. It has been 1.5 years after entering remission, and he is starting kindergarten. Lung CT scan and pathology should be analyzed to avoid missing diagnosis of PPB in patients with cystic or mixed cystic and solid lung lesions. Biopsies from cases of suspected PPB should be sent for expert pathology review. Two factors important to the successful application of the protocol are good supportive care and the multidisciplinary collaboration between medical facilities to provide proper resources during treatment. We hope to recreate more successful outcomes not only in Vietnam but also in all developing countries.
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Blastoma Pulmonar/diagnóstico , Blastoma Pulmonar/terapia , Humanos , Lactente , Masculino , VietnãRESUMO
The roots of Abrus precatorius (AP, Fabaceae) have traditionally been used in Vietnam and China for the treatment of inflammatory diseases such as stomatitis, asthma, bronchitis, and hepatitis. Therefore, in this study, we isolated 4-methoxylonchocarpin (ML), an anti-inflammatory compound present in AP, and studied its anti-inflammatory effects in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. In lipopolysaccharide (LPS)-stimulated macrophages, ML was found to inhibit nuclear factor (NF)-κB activation and tumor necrosis factor (TNF) and interleukin (IL)-6 expression by inhibiting LPS binding to Toll-like receptor 4 (TLR4) in vitro. Oral administration of ML in mice with TNBS-induced colitis suppressed colon shortening and colonic myeloperoxidase activity. ML treatment significantly inhibited the activation of nuclear factor (NF)-κB and phosphorylation of transforming growth factor ß-activated kinase 1 in the colon. Treatment with ML also inhibited TNBS-induced expression of IL-1ß, IL-17A, and TNF. While ML reduced the TNBS-induced expression of M1 macrophage markers such as arginase-2 and TNF, it was found to increase the expression of M2 macrophage markers such as arginase-1 and IL-10. In conclusion, oral administration of ML attenuated colitis in mice by inhibiting the binding of LPS to TLR4 on immune cells and increasing the polarization of M1 macrophages to M2 macrophages.
Assuntos
Abrus/imunologia , Anti-Inflamatórios/uso terapêutico , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Flavonas/uso terapêutico , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Diferenciação Celular , Células Cultivadas , Colite/induzido quimicamente , Colo/imunologia , Flavonas/química , Inflamação/induzido quimicamente , Interleucina-6 , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Ácido TrinitrobenzenossulfônicoRESUMO
Efforts to reduce tobacco use among school children need to be based on understanding of access to cigarettes by these subjects because previous studies indicated that enforcement of laws for controlling tobacco sales seems to not affect teen/school children because they can obtain cigarettes from different sources. This paper aims to describe access to and availability of cigarettes among school students (aged 13-15 years old) according to the data from GYTS Vietnam 2014. In GYTS, a national school-based survey of students of grades 8-10, our findings showed that about 15% school children are current smokers who smoke at home, and that they could easily buy cigarettes from stores (63.2%), or someone else (27.8%), or street vendors (9%). Notably, over 85% of school children answered that they were not refused because of their age. This high percentage was nearly the same in the North (85.7%), the Centre (92.5%), and the South (89.7%) of Viet Nam. These findings show that it is quite easy for school children to obtain cigarettes and this is a crucial challenge for policy makers aiming to reduce tobacco use among youth in general and school-age students in particular.
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Comportamento do Adolescente/psicologia , Comércio/estatística & dados numéricos , Fumar/epidemiologia , Produtos do Tabaco/provisão & distribuição , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Tabagismo/epidemiologia , Adolescente , Saúde Global , Humanos , Masculino , Vigilância da População , Prevalência , Instituições Acadêmicas , Fumar/psicologia , Estudantes/psicologia , Inquéritos e Questionários , Tabagismo/psicologia , Vietnã/epidemiologiaRESUMO
This study, using C57BL/6J mice with streptozotocin (STZ)-induced diabetes, aimed to determine whether Bifidobacterium species (spp.) both induces the expressions of proteins in the insulin signaling pathway and enhances the expressions of certain adipocytokines. The protein expressions of IκB kinase alpha (IKKα), IκB kinase beta (IKKß), nuclear factor-kappaB inhibitor alpha (IκBα), and the mitogen-activated protein kinase (MAPK) pathway were also investigated. Oral administration of Bifidobacterium spp. reduced blood glucose levels significantly and increased the protein expressions of insulin receptor beta, insulin receptor substrate 1, protein kinase B (Akt/PKB), IKKα, and IκBα. Extracellular-signal-regulated kinase 2 (ERK2) showed increased expression. Bifidobacterium spp. also induced the adiponectin expression and decreased both macrophage chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) expression. In addition, IKKß, c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase expressions showed no significant changes in both groups. In conclusion, Bifidobacterium spp. may be the promising bacteria for treating diabetes.
Assuntos
Bifidobacterium/fisiologia , Glicemia/metabolismo , Diabetes Mellitus Experimental/dietoterapia , Regulação da Expressão Gênica/efeitos dos fármacos , Insulina/sangue , Probióticos/farmacologia , Adiponectina/genética , Adiponectina/metabolismo , Administração Oral , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Insulina/genética , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Estreptozocina , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The intestinal microbiome might be an important contributor to the development of type 2 diabetes. This study was designed to test the hypothesis that oral administration of Bifidobacterium species (spp.) (including B. longum, B. bifidum, B. infantis, and B. animalis) may both ameliorate insulin resistance and reduce the expressions of inflammatory adipocytokines. Male Swiss-Webster mice fed a high-fat diet with or without oral administration of Bifidobacterium spp. for 5 weeks were subjected to an insulin tolerance test and an oral glucose tolerance test. Plasma levels of glucose at 30, 60, 90 and 120 min after insulin injection or glucose administration were significantly lower in the Bifidobacterium spp. than in the control group (P < 0.05), showing the beneficial effect of oral administration on insulin resistance in obese Swiss mice. In addition, Bifidobacterium spp. increased the adiponectin mRNA level and decreased those of monocyte chemoattractant protein 1 and interleukin 6 in non-diabetic C57BL/6J mice fed a normal diet, indicating a molecular mechanism which may ameliorate the inflammatory state, thereby reducing insulin resistance. In conclusion, oral administration of Bifidobacterium spp. improves insulin resistance and glucose tolerance in obese mice by reducing inflammation, as it does in the lean state.
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Adipocinas/genética , Adiponectina/genética , Bifidobacterium/fisiologia , Resistência à Insulina , Administração Oral , Animais , Quimiocina CCL2/genética , Diabetes Mellitus Tipo 2 , Dieta Hiperlipídica , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Interleucina-6/genética , Masculino , Camundongos , RNA Mensageiro/genéticaRESUMO
The rhizome of Polygala tenuifolia WILLD (PT, family Polygalaceae) has been used in traditional Chinese medicine for inflammation, dementia, amnesia, neurasthenia and cancer. The phosphoinositide 3-kinase (PI3K)/Akt inhibitor(s) was isolated from PT by using the cytoprotective phenotype of human immunodeficiency virus type 1 (HIV-1) Tat-transduced CHME5 cells against lipopolysaccharide/cycloheximide. We isolated 9 constituents (1)-(9) from ethyl acetate fraction of PT, which potently showed anti-cytoprotective effect against HIV-1 TAT-transduced cells. Of them, (9R)-(-)-9-peptandecanolide (2), a new compound named poligapolide, most potently abolished the cytoprotective effect of HIV-1 Tat-transduced CHME5 cells. The compound (2) inhibited the phosphorylation of Akt and its downstream molecule, glycogen synthase kinase-3 beta (GSK3ß) in PI3K/Akt cell survival signaling pathway, but did not suppress the phosphorylation of PI3K and pyruvate dehydrogenase lipoamide kinase isozyme 1. Based on these finding, poligapolide may abolish the cytoprotective phenotype of HIV-1 Tat-transduced CHME5 cells by inhibiting Akt phosphorylation in PI3K/Akt pathway.
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Lactonas/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Polygala/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Rizoma/química , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cicloeximida/antagonistas & inibidores , Cicloeximida/farmacologia , Relação Dose-Resposta a Droga , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Estrutura Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/isolamento & purificação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genéticaRESUMO
PURPOSE: CKD-516 is a benzophenone analog in which the B ring is modified by replacement with a carbonyl group. The study assessed CKD-516 as a vascular disrupting agent or anti-cancer drug. METHODS: To assess the effect of S516 on vascularization, we analyzed the effect on human umbilical vein endothelial cells (HUVECs). To determine the inhibition of cell proliferation of S516, we used H460 lung carcinoma cells. The alteration of microtubules was analyzed using immunoblot, RT-PCR and confocal imaging. To evaluate the anti-tumor effects of gemcitabine and/or CKD-516, H460 xenograft mice were treated with CKD-516 (2.5 mg/kg) and/or gemcitabine (40 mg/kg), and tumor growth was compared with vehicle-treated control. For histologic analysis, liver, spleen and tumor tissues from H460 xenograft mice were obtained 12 and 24 h after CKD-516 injection. RESULTS: Cytoskeletal changes of HUVECs treated with 10 nM S516 were assessed by immunoblot and confocal imaging. S516 disrupted tubulin assembly and resulted in microtubule dysfunction, which induced cell cycle arrest (G2/M). S516 markedly enhanced the depolymerization of microtubules, perhaps due to the vascular disrupting properties of S516. Interestingly, S516 decreased the amount of total tubulin protein in HUVECs. Especially, S516 decreased mRNA expression α-tubulin (HUVECs only) and ß-tubulin (HUVECs and H460 cells) at an early time point (4 h). Immunocytochemical analysis showed that S516 changed the cellular microtubule network and inhibited the formation of polymerized microtubules. Extensive central necrosis of tumors was evident by 12 h after treatment with CKD-516 (2.5 mg/kg, i.p.). In H460 xenografts, CKD-516 combined with gemcitabine significantly delayed tumor growth up to 57 % and 36 % as compared to control and gemcitabine alone, respectively. CONCLUSION: CKD-516 is a novel agent with vascular disrupting properties and enhances anti-tumor activity in combination with chemotherapy.
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Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzofenonas/farmacologia , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Valina/análogos & derivados , Animais , Antineoplásicos/administração & dosagem , Benzofenonas/administração & dosagem , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Mutantes , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Neoplasias/patologia , Tubulina (Proteína)/metabolismo , Carga Tumoral/efeitos dos fármacos , Valina/administração & dosagem , Valina/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , GencitabinaRESUMO
Malignant gliomas are the most common and fatal brain tumors in adults. In particular, the strong invasiveness of glioma cells into the normal brain tissue makes eradication of glioma very difficult. Matrix metalloproteinases (MMPs) play a pivotal role in glioma invasion, and thus controlling MMP expression has been suggested as an important therapeutic target for brain tumors. In the present study, we investigated the effect of protopanaxatriol ginsenoside Rh1 on MMP expressions in human astroglioma U87MG and U373MG cells. RT-PCR analysis showed that Rh1 inhibits the mRNA expressions of MMP-1, -3, and -9 in PMA-stimulated U87MG and U373MG cells. Rh1 also suppressed the promoter activities of MMP-1, -3 and -9. The ELISA, Western blot, and zymographic analyses revealed that Rh1 inhibits the protein expression and/or enzymatic activity of MMP-1, -3 and -9. In accordance with the strong inhibitory effects of Rh1 on MMPs, Rh1 efficiently inhibited the invasion and migration of U87MG and U373MG glioma cells as demonstrated by Matrigel invasion assay and wound healing assay. Further mechanistic studies revealed that Rh1 inhibits MAPK and PI3K/Akt signaling pathways and downstream transcription factors such as NF-κB and AP-1, which play an important role in MMP gene expressions. The data collectively suggest that ginsenoside Rh1 may have a therapeutic potential for malignant gliomas.
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Astrocitoma/enzimologia , Neoplasias Encefálicas/enzimologia , Metaloproteinases da Matriz/efeitos dos fármacos , Invasividade Neoplásica/prevenção & controle , Metástase Neoplásica/prevenção & controle , Inibidores de Proteases/farmacologia , Sapogeninas/farmacologia , Astrocitoma/patologia , Sequência de Bases , Western Blotting , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Humanos , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Microglial activation plays an important role in neurodegenerative diseases. Thus, controlling microglial activation is considered to be a promising therapeutic target for neurodegenerative diseases. In the present study, we found that lancemaside A, a triterpenoid saponin isolated from Codonopsislanceolata, inhibited iNOS and proinflammatory cytokines in LPS-stimulated BV2 microglial cells. By analyzing molecular mechanisms underlying the anti-inflammatory effects of lancemaside A, we found that lancemaside A selectively inhibited LPS-induced JNK phosphorylation among the three types of MAP kinases. A JNK-specific inhibitor, SP600125, like lancemaside A, significantly inhibited not only NO, TNF-α, and IL-6 productions, but also NF-κB and AP-1 activities, suggesting that JNK inhibition is largely involved in the anti-inflammatory mechanism of lancemaside A. Interestingly, both the lancemaside A and SP600125 inhibited ROS production by suppressing the expression and/or phosphorylation of NADPH oxidase subunit proteins, such as p47(phox), p67(phox), and gp91(phox). The antioxidant effects of lancemaside A and SP600125 appear to be related with an increase of hemeoxygenase-1 expression by both agents. Finally, we demonstrated the neuroprotective effects of lancemaside A and SP600125 in microglia-neuron coculture systems. Collectively, our data suggest that JNK pathway plays a key role mediating anti-inflammatory effects of lancemaside A in LPS-stimulated microglia.
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Anti-Inflamatórios não Esteroides/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Saponinas/farmacologia , Animais , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Interleucina-6/antagonistas & inibidores , Lipopolissacarídeos , Camundongos , Microglia/enzimologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng (family Araliaceae) is traditionally used as a remedy for cancer, inflammation, stress and aging. AIM OF STUDY: To explore whether ginsenosides Rg5 and Rh3, the main constituents of heat-processed ginseng (the root of Panax ginseng), could protect memory deficit. MATERIALS AND METHODS: We isolated ginsenosides Rh3 and Rg5 from heated-processed ginseng treated with and without human feces, respectively. Then we investigated their protective effects on memory impairment using the passive avoidance, Y-maze and Morris water maze tasks in mice. Memory deficit was induced in mice by the intraperitoneal injection of scopolamine. RESULTS: Ginsenosides Rg5 or Rh3 increased the latency time reduced by scopolamine in passive avoidance test. Treatment with ginsenoside Rg5 or Rh3 significantly reversed the lowered spontaneous alteration induced by scopolamine in Y-maze task. Ginsenoisde Rg5 or Rh3 (10 mg/kg) significantly shortened the escape latencies prolonged by treatment with scopolamine on the last day of training trial sessions in Morris water maze task. Furthermore, ginsenosides Rg5 and Rh3 inhibited acetylcholinesterase activity in a dose-dependent manner, with IC50 values of 18.4 and 10.2 µM, respectively. The inhibitory potency of ginsenoside Rh3 is comparable with that of donepezil (IC50=9.9 µM). These ginsenosides also reversed hippocampal brain-derived neurotrophic factor (BDNF) expression and cAMP response element-binding protein (CREB) phosphorylation reduced by scopolamine. Of them, ginsenoside Rh3 more potently protected memory deficit. CONCLUSIONS: Ginsenoside Rg5 and its metabolite ginsenoside Rh3 may protect memory deficit by inhibiting AChE activity and increasing BDNF expression and CREB activation.
Assuntos
Ginsenosídeos/uso terapêutico , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Acetilcolinesterase/metabolismo , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ginsenosídeos/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Camundongos , Camundongos Endogâmicos ICR , Fármacos Neuroprotetores/farmacologia , EscopolaminaRESUMO
Alcohol consumption is associated with a wide range of health and social consequences. It is also associated with a number of risk taking behaviours. These include illicit drug use and unsafe sex. Alcohol consumption appears to be increasing in Vietnam. The purpose of this paper is to examine the patterns of alcohol consumption and its relationship with a number of other risk taking behaviours amongst young people. Information was also obtained concerning leisure activities and use of health care. The paper also sets out to examine possible gender differences in relation to alcohol consumption and risk behaviour and to propose the development and implementation of alcohol monitoring and prevention programs in Vietnam. The study involved a cross-sectional, community survey using a standardised interview. This was conducted during face-to-face interviews with 1,408 young people aged 10-19 years. Respondents were recruited randomly through the lists of the households from 12 selected communes in three areas in Northern Vietnam. The findings presented here were part of a larger health risk behaviour survey. Levels of alcohol use were low. Overall, 16.5% of participants were experienced drinkers, and only 4% of them were current drinkers. Males were significantly more likely than females to report drinking. This study also showed that rates of alcohol consumption were associated with age, education, geographical area, gender, tobacco smoking, involvement in violence, watching television, computer use and playing computer games, wearing safety helmets and use of health services. Alcohol consumption tended to increase with age for both males and females. Alcohol and its effects on young people are clearly a growing public health issue in Vietnam. Because of this, more detailed behavioral research should be conducted into the relationship between alcohol consumption and other risky behaviours amongst young people. It is also recommended that alcohol harm reduction policies should be implemented and integrated into measures to reduce levels of other health problems such as HIV/AIDS and non communicable diseases. Such policies should ideally be evidence-based and evaluated.
RESUMO
Phosphatidylinositol 3-kinase (PI3K)/Akt inhibitors were isolated from the rhizome of Polygala tenuifolia WILLD (PT, Polygalaceae), which has been used in traditional Chinese medicine for inflammation, dementia, amnesia, neurasthenia and cancer, by activity-guided fractionation. For the assay of PI3K/Akt pathway, cytoprotective Tat-transduced CHME5 cells, which are the cytoprotective phenotype against lypopolysaccharide (LPS)/cycloheximide (CHX), were used. We isolated 4 anti-cytoprotective compounds, clionasterol (1), ethyl cholestan-22-enol (2), 3-O-ß-D-glucosyl ethyl cholestan-22-enol (3), and 3-O-ß-D-glucopyranosyl clionasterol (4) from EtOAc fraction of PT against Tat-transduced CHME5 cells. Of them, (1) and (2) most potently abolished cytoprotective effect of Tat-transduced CHME5 cells. These constituents (1) and (2) inhibited the activation of 3-phosphoinositide-dependent kinase 1 (PDK1) and its downstream molecules, Akt/glycogen synthase kinase (GSK)3ß, in PI3K/Akt cell survival signaling pathway, but did not suppress the activation of PI3K. Based on these finding, (1) and (2) may abolish the cytoprotective phenotype of Tat-transduced CHME5 cells by inhibiting PDK1 phosphorylation in PI3K/Akt pathway.
Assuntos
Colestanóis/farmacologia , Citoproteção/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Extratos Vegetais/farmacologia , Polygala/química , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Sitosteroides/farmacologia , Linhagem Celular , Colestanóis/isolamento & purificação , Cicloeximida , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Produtos do Gene tat/metabolismo , Humanos , Lipopolissacarídeos , Extratos Vegetais/química , Rizoma/química , Transdução de Sinais/efeitos dos fármacos , Sitosteroides/isolamento & purificação , Proteínas Virais/metabolismoRESUMO
INTRODUCTION: Laboratory capacity is needed in central Viet Nam to provide early warning to public health authorities of respiratory outbreaks of importance to human health, for example the outbreak of influenza A(H1N1) pandemic in 2009. Polymerase chain reaction (PCR) procedures established as part of a capacity-building process were used to conduct prospective respiratory surveillance in a region where few previous studies have been undertaken. METHODS: Between October 2008 and September 2010, nose and throat swabs from adults and children (approximately 20 per week) presenting with an acute respiratory illness to the Ninh Hoa General Hospital were collected. Same-day PCR testing and result reporting for 13 respiratory viruses were carried out by locally trained scientists. RESULTS: Of 2144 surveillance samples tested, 1235 (57.6%) were positive for at least one virus. The most common were influenza A strains (17.9%), with pandemic influenza A(H1N1) 2009 and seasonal H3N2 strain accounting for 52% and 43% of these, respectively. Other virus detections included: rhinovirus (12.4%), enterovirus (8.9%), influenza B (8.3%), adenovirus (5.3%), parainfluenza (4.7%), respiratory syncytial virus (RSV) (3.9%), human coronavirus (3.0%) and human metapneumovirus (0.3%). The detection rate was greatest in the 0-5 year age group. Viral co-infections were identified in 148 (6.9%) cases. DISCUSSION: The outbreak in 2009 of the influenza A(H1N1) pandemic strain provided a practical test of the laboratory's pandemic plan. This study shows that the availability of appropriate equipment and molecular-based testing can contribute to important individual and public health outcomes in geographical locations susceptible to emerging infections.