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1.
Bioorg Chem ; 143: 107066, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38185009

RESUMEN

Repeated chromatography of the CH2Cl2 and EtOAc soluble fractions from the methanol extract of Belamcanda chinensis root yielded six new sucrosephenylpropanoid esters (1-6) and twenty-one known compounds (7-27). The structures of 1-6 were elucidated using diverse nuclear magnetic resonance (NMR) techniques and high-resolution mass spectrometry (HRMS) data analysis, together with chemical methods. All the twenty-seven isolated compounds were evaluated for their anti-osteoclastogenic activities. Preliminary screening results revealed that compounds 1 and 19 exhibited strong effects against RANKL-induced osteoclast formation in RAW264.7 cells. In addition, the treatment of mouse bone marrow macrophages (BMMs) with compounds 1 and 19 significantly decreased RANKL-induced TRAP-positive multinucleated osteoclast formation in a concentration-dependent manner without affecting cell viability. Further bioassay investigation showed that compounds 1 and 19 inhibited the expression of some osteoclast-specific marker genes and the transcription factor nuclear factor of activated T cells cytoplasmic 1 (NFATc1) in response to RANKL. To the best of our knowledge, this is the first investigation of anti-osteoclastogenic activity for compounds isolated from B. chinensis.


Asunto(s)
Resorción Ósea , Isoflavonas , Animales , Ratones , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismo , Resorción Ósea/prevención & control , Diferenciación Celular , Factores de Transcripción NFATC/efectos de los fármacos , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Osteoclastos , Osteogénesis/efectos de los fármacos , Isoflavonas/química , Isoflavonas/farmacología , Raíces de Plantas/química
2.
Bioorg Med Chem Lett ; 30(8): 127049, 2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-32111435

RESUMEN

One achiral tetra-aryl cyclobutane [rheundulin A (1)] and three stilbene glycosides [rheundulins B-D (2-4)] were isolated from the methanol extract of Rheum undulatum L., along with eight known compounds (5-12). Structural determination of the new compounds (1-4) was accomplished using comprehensive spectroscopic methods. Compound 1 represents the first example of a dimeric stilbene linked via a cyclobutane ring from the Rheum genus. All isolates were screened for their inhibition against α-glucosidase. Among them, stilbene derivatives (5 and 6) showed strong inhibitory effects on α-glucosidase with IC50 values of 0.5 and 15.4 µM, respectively, which were significantly higher than that of the positive control, acarbose (IC50 = 126.8 µM). Rheundulin A (1) showed moderate α-glucosidase inhibition with an IC50 value of 80.1 µM. In addition, kinetic analysis and molecular docking simulation of the most active compound (5) with α-glucosidase were performed for the first time. Kinetic studies revealed that compound 5 competitively inhibited the active site of α-glucosidase (Ki = 0.40 µM), while 6 had a mixed-type inhibitory effect against α-glucosidase (Ki = 15.34 µM). Molecular docking simulations of 5 and 6 demonstrated negative-binding energies, indicating high proximity to the active site and tight binding to α-glucosidase enzyme.


Asunto(s)
Ciclobutanos/farmacología , Inhibidores de Glicósido Hidrolasas/farmacología , Extractos Vegetales/farmacología , Rheum/química , Rizoma/química , Estilbenos/farmacología , alfa-Glucosidasas/metabolismo , Ciclobutanos/química , Ciclobutanos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Humanos , Cinética , Simulación del Acoplamiento Molecular , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Estilbenos/química , Estilbenos/aislamiento & purificación , Relación Estructura-Actividad
3.
J Nat Prod ; 83(2): 323-332, 2020 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-31944695

RESUMEN

Seven new stilbene glycosides including three dimers (1-3) and four monomers (4-7) were isolated from the roots of Polygonum multiflorum along with nine previously identified stilbenes (8-16). In addition, two deglucosylated stilbenes, 2a and 3a, were also obtained as new dimeric stilbenes. The structures of the purified phytochemicals were elucidated by interpreting their spectroscopic data (NMR, HRMS, and ECD). To the best of our knowledge, this represents the first isolation of a phenylpropanoid (C6-C3) substituted with a stilbene unit (7) from the Polygonaceae family. In an in vitro enzyme assay with human recombinant protein tyrosine phosphatase-1B (PTP1B), compounds 2-5 showed weak PTP1B inhibition with an IC50 value range of 27.4-37.6 µM, while three deglucosylated stilbenes 2a, 3a, and 8a exhibited IC50 values of 2.1, 1.9, and 12.1 µM, respectively. The inhibition modes and binding mechanism of selected inhibitors (2a and 3a) were investigated using kinetic methods and molecular docking simulations.


Asunto(s)
Inhibidores Enzimáticos/química , Fallopia multiflora/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Estilbenos/química , Inhibidores Enzimáticos/aislamiento & purificación , Glicósidos/química , Humanos , Simulación del Acoplamiento Molecular , Fitoquímicos , Raíces de Plantas/química , Polygonaceae/química , Polygonum/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Proteína Tirosina Fosfatasa no Receptora Tipo 1/química , Estilbenos/aislamiento & purificación
4.
Int J Mol Sci ; 21(24)2020 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-33327489

RESUMEN

Albanol B (ABN-B), an arylbenzofuran derivative isolated from mulberries, has been shown to have anti-Alzheimer's disease, anti-bacterial and antioxidant activities. The aim of this study was to investigate the anti-cancer effect of this compound against lung cancer cells. The results show that ABN-B inhibited the proliferation of four human lung cancer cell lines (A549, BZR, H1975, and H226) and induced apoptosis, based on the cleavage of caspase-7 and PARP (poly (ADP-ribose) polymerase), as well as the downregulation of Bcl-2. ABN-B also induced cell cycle arrest at G2/M by down-regulating the expression of CKD1 (cyclin-dependent kinase 1) and cyclin B1, but up-regulating p21 (cyclin-dependent kinase inhibitor 1) expression. Notably, ABN-B increased the production of mitochondrial reactive oxygen species (ROS); however, treatment with mito-TEMPO (a specific mitochondrial antioxidant) blocked ABN-B-induced cell cycle arrest at G2/M and apoptosis, as well as the up-regulation of p21 and down-regulation of CDK1 and cyclin B1 induced by ABN-B. At the molecular level, ABN-B-induced mitochondrial ROS production increased the phosphorylation levels of AKT (protein kinase B) and ERK1/2 (extracellular signal-regulated kinase 1/2), while the inhibition of these kinases blocked the ABN-B-induced up-regulation of p21 and down-regulation of CDK1 and cyclin B1. Moreover, ABN-B significantly suppressed tumor growth in Ex-3LL (Lewis lung carcinoma) tumor-bearing mice. Taken together, these results suggest that ABN-B can exert an anti-cancer effect by inducing apoptosis and cell cycle arrest at G2/M through mitochondrial ROS production in lung cancer cells.


Asunto(s)
Benzofuranos/química , Flavonoides/química , Mitocondrias/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Benzofuranos/farmacología , Flavonoides/farmacología , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Proteína de la Leucemia Promielocítica con Dedos de Zinc/metabolismo , Especies Reactivas de Oxígeno/metabolismo
5.
Bioorg Chem ; 83: 105-110, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30343203

RESUMEN

Of the 32 Trichosanthes species in China, T. kirilowii Maxim. is the most renowned species used in traditional Chinese medicine and has diverse pharmacological properties. However, most of the phytochemical studies of T. kirilowii have focused on the fruits and seeds. In our investigation of the chemical constituents of T. kirilowii roots, two previously undescribed sterols [trichosanhemiketal A and B (1 and 2)], together with 13 known compounds, were isolated and their structures were elucidated. To the best of our knowledge, this represents the first isolation of compounds with a 13,14-seco-13,14-epoxyporiferastane (1-2) skeleton from the Cucurbitaceae family. The anti-inflammatory activity of the isolated compounds was determined through an analysis of their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells. Of the compounds, 4, 5, 6, and 8 showed significant inhibitory activities, with IC50 values of 8.5, 15.1, 25.4, and 28.5 µM, respectively. In addition, compound 4 inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression in a concentration-dependent manner.


Asunto(s)
Ciclooxigenasa 2/metabolismo , Inhibidores Enzimáticos/farmacología , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Raíces de Plantas/química , Trichosanthes/química , Animales , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Humanos , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Conformación Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/metabolismo , Células RAW 264.7 , Relación Estructura-Actividad
6.
Clin Infect Dis ; 64(5): 656-663, 2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28034883

RESUMEN

Background: Early prediction of severe dengue could significantly assist patient triage and case management. Methods: We prospectively investigated 7563 children with ≤3 days of fever recruited in the outpatient departments of 6 hospitals in southern Vietnam between 2010 and 2013. The primary endpoint of interest was severe dengue (2009 World Health Organization Guidelines), and predefined risk variables were collected at the time of enrollment to enable prognostic model development. Results: The analysis population comprised 7544 patients, of whom 2060 (27.3%) had laboratory-confirmed dengue; nested among these were 117 (1.5%) severe cases. In the multivariate logistic model, a history of vomiting, lower platelet count, elevated aspartate aminotransferase (AST) level, positivity in the nonstructural protein 1 (NS1) rapid test, and viremia magnitude were all independently associated with severe dengue. The final prognostic model (Early Severe Dengue Identifier [ESDI]) included history of vomiting, platelet count, AST level. and NS1 rapid test status. Conclusions: The ESDI had acceptable performance features (area under the curve = 0.95, sensitivity 87% (95% confidence interval [CI], 80%-92%), specificity 88% (95% CI, 87%-89%), positive predictive value 10% (95% CI, 9%-12%), and negative predictive value of 99% (95% CI, 98%-100%) in the population of all 7563 enrolled children. A score chart, for routine clinical use, was derived from the prognostic model and could improve triage and management of children presenting with fever in dengue-endemic areas.


Asunto(s)
Pacientes Ambulatorios , Dengue Grave/diagnóstico , Dengue Grave/epidemiología , Algoritmos , Biomarcadores , Niño , Preescolar , Virus del Dengue/clasificación , Virus del Dengue/genética , Femenino , Humanos , Masculino , Nomogramas , Oportunidad Relativa , Vigilancia de la Población , Pronóstico , Estudios Prospectivos , Curva ROC , Dengue Grave/virología , Evaluación de Síntomas , Factores de Tiempo , Vietnam/epidemiología
7.
Bioorg Med Chem Lett ; 27(13): 2946-2952, 2017 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-28506750

RESUMEN

A phytochemical investigation into the bark of Erythrophleum fordii yielded four new compounds, two new cassaine diterpenoids (erythrofordin T and U, 1 and 2) and two new cassaine diterpenoid amines (erythroformine A and B, 6 and 7), as well as nine known compounds. We report for the first time the isolation of erythrofordin V (3) from a natural source and that of the remaining eight known diterpenoids (4-5, 8-13) from E. fordii. All structures were elucidated using spectroscopic analysis. Cytotoxic activity of the isolated compounds (1-13) was examined in vitro against three non-small cell lung cancer cell lines (A549, NCI-H1975, and NCI-H1229) using the MTT assay. Cassaine diterpene amines (6-10, 12, 13) exhibited potent cytotoxic activity against all three cell lines with IC50 values between 0.4µM and 5.9µM. Erythroformine B (7) significantly induced apoptosis in all three cancer cells in a concentration-dependent manner.


Asunto(s)
Alcaloides/farmacología , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Diterpenos/farmacología , Fabaceae/química , Neoplasias Pulmonares/tratamiento farmacológico , Corteza de la Planta/química , Abietanos , Alcaloides/química , Alcaloides/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Diterpenos/química , Diterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias Pulmonares/patología , Estructura Molecular , Relación Estructura-Actividad
8.
Acta Paediatr ; 106(10): 1608-1616, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28685899

RESUMEN

AIM: This study presents results from an intervention designed to improve identification and response to abusive head trauma in a tertiary paediatric hospital in Vietnam. METHODS: One hundred and sixteen healthcare professionals (paediatric medical and nursing staff) completed a clinical training programme and participated in its evaluation. A pre-post-test and follow-up design was used to evaluate the outcomes. Questionnaires were used to collect data prior to training, at six weeks and at six months. Generalised linear modelling was used to examine changes in diagnostic skills and knowledge of the consequences of shaken baby syndrome (SBS) (a form of abusive head trauma), its prevention and treatment. RESULTS: At baseline, awareness and knowledge reflected no former abusive head trauma training. Following the intervention, participants had an increased awareness of shaken baby syndrome and the potential consequences of shaking infants and had acquired techniques to inform parents how to manage the crying infant. CONCLUSION: The intervention was effective in raising awareness of shaken baby syndrome and its consequences amongst the participating healthcare professionals in Vietnam. Training can improve detection and prevention of abusive head trauma, and the intervention has the potential to be adapted for similar settings internationally.


Asunto(s)
Síndrome del Bebé Sacudido/diagnóstico , Competencia Clínica , Humanos , Estudios Longitudinales , Prevención Secundaria , Síndrome del Bebé Sacudido/prevención & control , Vietnam
9.
Bioorg Med Chem Lett ; 26(12): 2788-2794, 2016 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-27156775

RESUMEN

Detailed phytochemical investigation from the root bark of Morus alba resulted in the isolation of eleven new compounds, including seven 2-arylbenzofuran derivatives (morusalfurans A-G), three flavonoids (morusalnols A-C), and one geranylated stilbene (morusibene A), as well as 22 known compounds. The structures of the identified compounds were elucidated based on a comprehensive analysis of spectroscopic data and Mosher's method. Compounds 2, 3, 6-8, 11, 23, 24, and 29 showed potent inhibition of PL in comparison with the positive control treatment (orlistat, IC50=0.012µM), with IC50 values ranging from 0.09 to 0.92µM.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Lipasa/antagonistas & inhibidores , Páncreas/efectos de los fármacos , Corteza de la Planta/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Humanos , Lipasa/metabolismo , Estructura Molecular , Páncreas/enzimología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Relación Estructura-Actividad
10.
J Med Virol ; 87(6): 904-12, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25648607

RESUMEN

Genetic variability makes influenza virus to escape the immunity and causes yearly epidemics. Monitoring those changes is necessary for vaccine selection. In addition, H3N2 viruses were considered to be seeded from Southeast Asia before spreading globally. This study described the molecular epidemiology of influenza A during the post-pandemic season 2010-2011 in Vietnam. Nasopharyngeal samples were collected from children with respiratory infections at Children's Hospital 2, Ho Chi Minh City. The HA, NA, M genes were amplified, sequenced and analyzed. Thirty-five of 1,082 (3.2%) patients were positive for influenza A, including 14 pandemic H1N1 2009 (H1N1pdm09) and 21 H3N2 infections. H3N2 was dominant in the rainy season (May-October 2010) while H1N1pdm09 was dominant in the dry season (November 2010-April 2011). Phylogenetic analysis showed that Vietnamese H1N1pdm09 sequences in 2010-2011 formed the distinct cluster, with other contemporary Asian and 2012-American sequences, suggesting a possible common ancestor. All were oseltamivir-sensitive except two strains carrying S247N and D199N in NA which reduced the neuraminidase inhibitor susceptibility. The Vietnamese H3N2 viruses in mid-2010 belonged to the emerging subclade Perth10/2010, which then spread worldwide in 2011. The Vietnamese influenza viruses were well matched with the Southern Hemisphere vaccine formulation. Mutations at antigenic sites were also identified in these viruses. Surveillance of influenza viruses in tropical countries is important not only for development of their prevention and control strategies but also for earlier identification of the newly emerged strains that may be selected for future vaccine.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Gripe Humana/epidemiología , Gripe Humana/virología , Adolescente , Antivirales/farmacología , Antivirales/uso terapéutico , Niño , Preescolar , Femenino , Genes Virales , Hospitalización , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/tratamiento farmacológico , Masculino , Epidemiología Molecular , Filogenia , Estaciones del Año , Análisis de Secuencia de ADN , Factores de Tiempo , Vietnam/epidemiología
11.
Trop Med Int Health ; 18(12): 1444-51, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24134427

RESUMEN

OBJECTIVE: To assess the proportion of, and reasons for, households not utilising the policy of free healthcare for children under 6 years of age (FCCU6) for hospitalisation with diarrhoea, and assess the risk of catastrophic expenditure for households that forgo FCCU6 and pay out of pocket. METHODS: Invoices detailing insurance information and charges incurred from 472 hospitalised diarrhoeal cases in one paediatric hospital in Ho Chi Minh City were retrieved. Hospital charges and the utilisation of elective services were analysed for patients utilising and not utilising FCCU6. Associations between socio-economic factors with non-utilisation of FCCU6 were evaluated. RESULTS: Overall, 29% of patients were FCCU6 non-users. The FCCU6 non-users paid a median hospital charge of $29.13 (interquartile range, IQR: $18.57-46.24), consuming no more than 1.4% of a medium-income household's annual income. Seventy per cent of low-income FCCU6 non-users utilised less-expensive elective services, whereas only 43% of medium income patients and 21% of high-income patients did (P = 0.036). Patients from larger households and those with a parent working in government were more likely to use FCCU6. CONCLUSIONS: The rate of FCCU6 non-usage in this study population was 29%. A significant proportion of those that did not use FCCU6 was from lower income households and may perceive a justifiable cost-benefit ratio when forgoing FCCU6. Although a single diarrhoeal hospitalisation is unlikely to induce a catastrophic expenditure, FCCU6 non-usage may disproportionately increase the risk of catastrophic expenditure for lower income households over multiple illnesses.


Asunto(s)
Diarrea/epidemiología , Hospitalización/estadística & datos numéricos , Cobertura Universal del Seguro de Salud/estadística & datos numéricos , Factores de Edad , Preescolar , Diarrea/economía , Diarrea/terapia , Femenino , Financiación Personal/estadística & datos numéricos , Costos de la Atención en Salud/estadística & datos numéricos , Política de Salud , Hospitales Pediátricos/estadística & datos numéricos , Humanos , Renta/estadística & datos numéricos , Lactante , Masculino , Centros de Atención Terciaria/economía , Centros de Atención Terciaria/estadística & datos numéricos , Cobertura Universal del Seguro de Salud/organización & administración , Vietnam/epidemiología
12.
Pract Lab Med ; 37: e00339, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37886110

RESUMEN

Backgrounds and aims: The aim of this study is to provide a good approach for a quantitative EQA scheme assigned value with limited resources. Materials and methods: Twelve lyophilized EQA items were distributed to participants in 2021 from North to Southeast Vietnam to measure the concentration of nine parameters, including glucose, urea, creatinine, cholesterol, triglyceride, uric acid, AST, ALT, and GGT. The consensus value of the expert group and all participants were calculated and statistically compared to choose the most appropriate consensus value. Results: Fifty-nine laboratories attended the EQA scheme, including an expert group using automatic biochemistry analyzers (AAs) and all participants with auto and semi-auto biochemistry (SAA) analyzers. Consensus values of six per nine parameters were different between the two groups for at least two EQA items, including glucose, creatinine, cholesterol, uric acid, AST, and ALT. The coefficients of variation of glucose, urea, creatinine, triglycerides, uric acid, and GGT in the expert group were significantly lower than those in all the participants. Conclusion: Using the consensus values of expert groups as the assigned values of the EQA program is a relevant strategy to increase testing quality in developing countries with limited resources, such as Vietnam.

13.
Egypt Heart J ; 75(1): 75, 2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37642755

RESUMEN

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker used for the diagnosis of heart failure. There is a relationship between NT-proBNP levels and body mass index (BMI). The study aimed to explore the impact of BMI on NT-proBNP concentrations and to examine whether other factors independent of or combined with BMI affect NT-proBNP values in patients with heart failure. RESULTS: A total of 293 participants were recruited. The mean age was 68.9 ± 13.2 years, males accounted for 46.4% of the total cohort, the mean BMI was 23.1 ± 4.0 kg/m2, and the median NT-proBNP level was 3776 (1672-8806) pg/ml. There was an inverse relationship between BMI and log NT-proBNP (r = - 0.29; p < 0.001, Spearman correlation). Each standard deviation increase in BMI (4 kg/m2) was associated with a 7% decrease in NT-proBNP values in the total cohort. The independent inverse determinants of NT-proBNP other than BMI were male gender and eGFR, while the variables directly correlated to NT-proBNP were LVEF ≤ 40% and NYHA class III-IV heart failure. CONCLUSIONS: There is an inverse association between BMI and NT-proBNP levels. However, the correlation is weak, and there are other variables that have a significant impact on the NT-proBNP values as well. The NT-proBNP levels are still valuable in the diagnosis of heart failure regardless of BMI status.

14.
Phytochemistry ; 213: 113769, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37343738

RESUMEN

Four undescribed compounds (two 1,5-anhydro-d-glucitol derivatives and two galloyl derivatives) and fourteen known compounds were isolated and structurally identified from leaves of Acer ginnala Maxim. (Amur maple). Structures and absolute configurations of the four undescribed compounds were determined using extensive analysis of NMR spectroscopic, HRESI-MS, modified Mosher ester method, and comparison with spectroscopic data of known compounds. Bioactivity evaluation revealed that the isolated 1,5-anhydro-d-glucitol derivative, galloylated flavonol rhamnosides, and galloylated flavanols had inhibitory effects on both protein tyrosine phosphatase-1B (PTP1B, IC50 values ranging of 3.46-12.65 µM) and α-glucosidase (IC50 values ranging of 0.88-6.06 µM) in comparison with a positive control for PTP1B (ursolic acid, IC50 = 5.10 µM) or α-glucosidase (acarbose, IC50 = 141.62 µM). A combination of enzyme kinetic analysis and molecular docking provided additional evidence in favor of their inhibitory activities and mechanism. These data demonstrate that A. ginnala Maxim. together with its constituents are promising sources of potent candidates for developing novel anti-diabetic medications.


Asunto(s)
Acer , Inhibidores Enzimáticos , Inhibidores Enzimáticos/química , alfa-Glucosidasas/metabolismo , Acer/química , Acer/metabolismo , Flavonoides/metabolismo , Sorbitol/química , Sorbitol/farmacología , Simulación del Acoplamiento Molecular , Cinética , Hojas de la Planta/química , Inhibidores de Glicósido Hidrolasas/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 1
15.
Phytochemistry ; 197: 113100, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35144153

RESUMEN

In this study, we present the first investigation of Hedera rhombea Bean fruit, which led to the isolation of six undescribed compounds including two megastigmane glucosides, two rare 1,4-dioxane neolignanes, and two quinic acid derivatives, together with 26 known compounds. Their structures and absolute configurations were elucidated by extensive analysis of NMR spectroscopic data, HRMS, and ECD calculations. This is the first report on the isolation of methyl 3-O-caffeoyl-5-O-p-coumaroylquinate from a natural source. Among the isolated compounds, falcarindiol and caffeoyltryptophan showed significant PTP1B inhibition with IC50 values of 7.32 and 16.99 µM, respectively, compared to those of the positive controls [sodium orthovanadate (IC50 = 17.96 µM) and ursolic acid (IC50 = 4.53 µM)]. These two compounds along with several other compounds displayed significant α-glucosidase inhibitions with IC50 values ranging from 12.88 to 91.89 µM, stronger than that of the positive control (acarbose, IC50 = 298.07 µM). Enzyme kinetic analysis indicated that caffeoyltryptophan and falcarindiol displayed competitive and mixed-type PTP1B inhibition, respectively, whereas the α-glucosidase inhibition type was mixed-type for caffeoyltryptophan and uncompetitive (rarely reported for a-glucosidase inhibitors) for falcarindiol. In addition, molecular docking results showed that these active compounds exhibited good binding affinities toward both PTP1B and α-glucosidase with negative binding energies. The results of the present study demonstrate that these active compounds might be beneficial in the treatment of type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hedera , Frutas/química , Inhibidores de Glicósido Hidrolasas/química , Hedera/metabolismo , Cinética , Simulación del Acoplamiento Molecular , Estructura Molecular , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , alfa-Glucosidasas/metabolismo
16.
Fitoterapia ; 162: 105294, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36058474

RESUMEN

One new 1,4-bis-phenyl-1,4-butanedione glycoside (14), one new eudesmane-type sesquiterpenoid (16), and 16 known compounds were isolated from the leaves and stems of Nelumbo nucifera Gaertn. The structures of the isolated compounds were elucidated by interpretation of their 1D and 2D NMR spectroscopic and HRESIMS data. Time-dependent density functional theory calculations and Electronic Circular Dichroism (ECD) spectroscopy was used to determine absolute configurations of the new eudesmane-type sesquiterpenoid (16). All the isolated compounds were examined for their antiosteoclastogenic activity. Preliminarily results of the TRAP staining on RAW 264.7 cells indicated that compounds 1 and 11 possess potential inhibitory effects on RANKL-induced osteoclast formation. Further bioassay investigation was carried out to reveal that compounds 1 and 11 suppressed RANKL-induced osteoclast formation in a concentration-dependent manner with the inhibition up to 55% and 78% at the concentration of 10 µM, respectively. In addition, the structure-activity relationship analysis showed that the 1,3-dioxole substitute and the double bond at C-6a/C-7 in the aporphine skeleton may be responsible for the antiosteoclastogenic activity. The findings provided valuable insights for the discovery and structural modification of aporphine alkaloids as the antiosteoclastogenic lead compounds.


Asunto(s)
Alcaloides , Aporfinas , Lotus , Nelumbo , Sesquiterpenos de Eudesmano , Alcaloides/farmacología , Aporfinas/farmacología , Dioxoles , Glicósidos/análisis , Estructura Molecular , Nelumbo/química , Hojas de la Planta/química
17.
Clin Lab ; 57(5-6): 397-401, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21755831

RESUMEN

BACKGROUND: Rubella virus (RV) infection during the first trimester of pregnancy often leads to severe birth defects known as congenital rubella syndrome (CRS). METHODS: A premature newborn male was clinically diagnosed as CRS with cataracts, congenital heart defects, microcephaly, hepatosplenomegaly, and thrombocytopenia. The infection was confirmed serologically and molecularly. RESULTS: The RV was characterized and clustered with the 2B genotype. CONCLUSIONS: The integrated description of clinical features, serological and molecular data provide a baseline for diagnosis and control of rubella and CRS in Vietnam. This is the first report of molecular investigation of wildtype RV strain in Vietnam, thus contributing to the documentation of RV's worldwide distribution.


Asunto(s)
Anomalías Múltiples/etiología , Enfermedades del Prematuro/virología , Virus de la Rubéola/aislamiento & purificación , Rubéola (Sarampión Alemán)/congénito , Anomalías Múltiples/virología , Adulto , Catarata/congénito , Catarata/etiología , ADN Viral/genética , Femenino , Retardo del Crecimiento Fetal/etiología , Cardiopatías Congénitas/etiología , Humanos , Recién Nacido , Recien Nacido Prematuro , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Microcefalia/etiología , Datos de Secuencia Molecular , Filogenia , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Primer Trimestre del Embarazo , Rubéola (Sarampión Alemán)/epidemiología , Rubéola (Sarampión Alemán)/transmisión , Rubéola (Sarampión Alemán)/virología , Virus de la Rubéola/clasificación , Virus de la Rubéola/genética , Vietnam/epidemiología
18.
J Agric Food Chem ; 69(44): 12994-13005, 2021 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-34694780

RESUMEN

As part of our continuous program to identify new potential candidates for controlling osteolytic bone diseases from natural products, the alkaloid fraction of barley (Hordeum vulgare var. hexastichon) grass (HVA) significantly inhibited RANKL-induced osteoclast formation and protected mice from LPS-induced bone loss. A phytochemical investigation of HVA afforded nine indole alkaloids, including one new compound [hordeumin A (1)] and eight known analogues (2-9). Of them, four (1, 2, 4, and 5) were anti-osteoclastogenic compounds. Of these four, compound 5 significantly suppressed RANKL-induced osteoclast formation, actin ring formation, and bone resorption in a concentration-dependent manner. It also suppressed the RANKL-induced NF-κB and MAPK signaling pathways and the activation of c-Fos and NFATc1. Compound 5 also reduced the expression levels of osteoclast-specific marker genes, including TRAP, CtsK, DC-STAMP, OSCAR, and MMP9. Our findings suggest that HVA and its alkaloid constituents could be valuable candidates for the prevention and treatment of osteolytic bone diseases.


Asunto(s)
Resorción Ósea , Hordeum , Animales , Resorción Ósea/tratamiento farmacológico , Diferenciación Celular , Alcaloides Indólicos , Ratones , FN-kappa B , Factores de Transcripción NFATC , Osteoclastos , Osteogénesis , Poaceae , Ligando RANK/genética
19.
Phytochemistry ; 188: 112791, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34082339

RESUMEN

An undescribed 1,3-diphenylpropane derivative, kazinol V and six undescribed prenylated flavonoids, broussonols F-H and broussonols K-M were isolated from the roots of Broussonetia kazinoki Siebold, together with 12 known compounds. This is the first report of the isolation and structure determination of broussonol I from a natural source. The chemical structure of the undescribed compounds was determined using conventional NMR and HRMS data. Absolute configurations were assigned using time-dependent density functional theory calculations and Electronic Circular Dichroism (ECD) spectroscopy. The isolated compounds were screened for their effects on RANKL-induced osteoclast formation using RAW264.7 cells. Among them, broussonols F, G, and K showed strong, dose-dependent antiosteoclastogenic activities. Broussonol K exhibited the most potent inhibitory activity and possessed bone resorption suppressive activity.


Asunto(s)
Broussonetia , Animales , Flavonoides/farmacología , Ratones , Extractos Vegetales , Células RAW 264.7
20.
Fitoterapia ; 151: 104880, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33711431

RESUMEN

Xanthones (9H-xanthene-9-ones) are considered to be very promising compounds due to a variety of interesting biological and pharmacological activities. In this study, column chromatography of the methanol extract of the Garcinia mangostana L. pericarps resulted in the isolation of four new xanthones (garcinoxanthones SV, 1-4) and five known analogs including garcinone E (5), 11-hydroxy-1-isomangostin (6) mangostenone E (7), 1,3,6,7-tetrahydroxyxanthone (8), and α-mangostin (9). The structures of the new compounds were elucidated by NMR, HRESIMS, and ECD spectra. Compound 8 (1,3,6,7-tetrahydroxyxanthone) was found from the G. mangostana pericarps for the first time. All the isolated compounds (1-8) were evaluated for their 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and cytotoxicity in vitro against three human cancer cell lines including SK-LU-1, MCF7, and HT-29 cell lines. Compounds 3, 5, and 8 exhibited significant DPPH scavenging capacity with IC50 values of 68.55, 63.05, and 28.45 µM, respectively, in comparison with ascorbic acid (IC50 = 48.03 µM). Compounds 5 and 8 showed moderate cytotoxic effects against the three human cancer cell lines with IC50 value ranges of 19.86-27.38 µM.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Garcinia mangostana/química , Xantonas/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Frutas/química , Células HT29 , Humanos , Células MCF-7 , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Vietnam , Xantonas/aislamiento & purificación
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