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OBJECTIVE: The aim of this study was to determine the associations between dietary diversity and risk of dyslipidemia in Japanese workers. METHODS: The cross-sectional study included 1399 participants aged 20-63 years and the longitudinal study included 751 participants aged 20-60 years in 2012-2013 (baseline) who participated at least once from 2013 to 2017 with cumulative participation times of 4.9 times. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity score (DDS) was determined using the Quantitative Index for Dietary Diversity. Dyslipidemia was diagnosed when at least one of the following conditions was met: hypertriglyceridemia, high LDL-cholesterol, low HDL-cholesterol, high non-HDL-cholesterol, and a history of dyslipidemia. Multivariable logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for dyslipidemia with control of confounding factors in cross-sectional analysis. Generalized estimating equations were used for calculating the ORs (95% CI) for dyslipidemia in the follow-up period according to the DDS at baseline with control of confounding factors in longitudinal analysis. RESULTS: Cross-sectional analysis showed that the highest DDS reduced the odds of dyslipidemia in men (OR [95% CI] in Tertile 3: 0.67 [0.48-0.95], p value = 0.023). In longitudinal analysis, a moderate DDS reduced the risk of dyslipidemia (OR [95% CI] in Tertile 2: 0.21 [0.07-0.60], p value = 0.003) in women. CONCLUSIONS: The results of cross-sectional analysis in this study suggest that the higher diversity of diet might reduce the presence of dyslipidemia in men and the results of longitudinal analysis suggest that a moderate DDS might reduce the risk of dyslipidemia in women. Further studies are needed since the results of cross-sectional and longitudinal analyses in this study were inconsistent.
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Soluble epoxide hydrolase (sEH) is essential for converting epoxy fatty acids, such as epoxyeicosatrienoic acids (EETs), into their dihydroxy forms. EETs play a crucial role in regulating blood pressure, mediating anti-inflammatory responses, and modulating pain, making sEH a key target for therapeutic interventions. Current research is increasingly focused on identifying sEH inhibitors from natural sources, particularly marine environments, which are rich in bioactive compounds due to their unique metabolic adaptations. In this study, the sEH inhibitory activities of ten cembranoid diterpenes (1-10) isolated from the soft coral Sinularia maxima were evaluated. Among them, compounds 3 and 9 exhibited considerable sEH inhibition, with IC50 values of 70.68 µM and 78.83 µM, respectively. Enzyme kinetics analysis revealed that these two active compounds inhibit sEH through a non-competitive mode. Additionally, in silico approaches, including molecular docking and molecular dynamics simulations, confirmed their stability and interactions with sEH, highlighting their potential as natural therapeutic agents for managing cardiovascular and inflammatory diseases.
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Antozoos , Diterpenos , Epóxido Hidrolasas , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Epóxido Hidrolasas/antagonistas & inhibidores , Epóxido Hidrolasas/metabolismo , Antozoos/química , Animales , Diterpenos/farmacología , Diterpenos/química , Diterpenos/aislamiento & purificación , Cinética , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/químicaRESUMEN
The aim of this work was to evaluate the conformity of intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), and verify the accuracy of the planning and delivery system used in this work based on the AAPM TG-119 protocol. The Eclipse 13.6 treatment planning system (TPS) was used to plan the TG-119 test suite, which included four test cases: MultiTarget, Prostate, Head/Neck, and C-Shape for IMRT and VMAT techniques with 6 MV and 10 MV acceleration voltages. The results were assessed and discussed in terms of the TG-119 protocol and the results of previous studies. In addition, point dose and planar dose measurements were done using a semiflex ion chamber and an electronic portal imaging device (EPID), respectively. The planned doses of all test cases met the criteria of the TG-119 protocol, except those for the spinal cord of the C-Shape hard case. There were no significant differences between the treatment planning doses and the doses given in the TG-119 report, with p-values ranging from 0.974 to 1 (p > 0.05). Doses to the target volumes were similar in the IMRT and VMAT plans, but the organs at risk (OARs) doses were different depending on the test case. The planning results showed that IMRT is more conformal than VMAT in certain cases. For the point dose measurements, the confidence limit (CLpoint) of 0.030 and 0.021 were better than the corresponding values of 0.045 and 0.047 given in the TG-119 report for high-dose and low-dose areas, respectively. Regarding the planar dose measurements, the CLplanar value of 0.38 obtained in this work was lower than that given in the TG-119 report (12.4). It is concluded that the dosimetry measurements performed in this study showed better confidence limits than those provided in the TG 119 report. IMRT remains more conformal in certain circumstances than the more progressive VMAT. When selecting the method of delivering a dose to the patient, several factors must be considered, including the radiotherapy technique, energy, treatment site, and tumour geometry.
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Three undescribed solalodine-type glycoalkaloids, named solanigrinoside A-C (1-3), and six known compounds (4-9) were isolated from the whole plants of Solanum nigrum. Their structures were elucidated based on analysis of HR-ESI-MS, 1D- and 2D-NMR spectral data, and comparison with those reported in literatures. The solanigrinoside A-C (1-3), solasodine (4), and 3-acetoxysolasodine (5) exhibited cytotoxic effects against LU-1, Hep-G2, and MCF-7 cells with IC50 values in range from 4.6â µM to 56.2â µM. Compound 2 showed the significant cytotoxic activity with corresponding IC50 values of 5.7â µM, 7.9â µM, and 4.6â µM, respectively.
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Antineoplásicos Fitogénicos , Ensayos de Selección de Medicamentos Antitumorales , Alcaloides Solanáceos , Solanum nigrum , Humanos , Solanum nigrum/química , Alcaloides Solanáceos/farmacología , Alcaloides Solanáceos/química , Alcaloides Solanáceos/aislamiento & purificación , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Supervivencia Celular/efectos de los fármacos , Conformación MolecularRESUMEN
Soluble epoxide hydrolase (sEH) inhibitory activity guided fractionation and isolation of two new isocucurbic acid derivatives (1 and 2) and nine known compounds (3-11) from the flowers of Chrysanthemum indicum L. Their structures were elucidated on the basis of spectroscopic data interpretation and comparison with those reported in previous studies. Luteolin (3), acacetin-7-O-ß-D-glucopyranoside (6), and methyl 3,4-di-O-caffeoylquinate (10) displayed sEH inhibitory activities with IC50 values ranging from 13.7±3.6 to 20.8±0.4â µM. Enzyme kinetic analysis revealed that 3, 6, and 10 were non-competitive inhibitors with Ki values of 14.8±0.5, 31.2±0.8, and 3.9±0.2â µM, respectively. Additionally, molecular docking studies indicated compound 10 had the ability to form six hydrogen bonds at sEH active site, resulting binding energy as low as -9.58â Kcal/mol.
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AIMS: The study aimed at determining 5-year incidence and prediction nomogram for new-onset type 2 diabetes (T2D) in a middle-aged population in Vietnam. METHODS: A population-based prospective study was designed to collect socio-economic, anthropometric, lifestyle and clinical data. Five-year T2D incidence was estimated and adjusted for age and sex. Hazard ratio (HR) for T2D was investigated using discrete-time proportional hazards model. T2D prediction model entering the most significant risk factors was developed using the multivariable logistic-regression algorithm. The corresponding prediction nomogram was constructed and checked for discrimination, calibration and clinical usefulness. RESULTS: The age- and sex-adjusted incidence was 21.0 cases (95% CI: 12.2-40.0) per 1000 person-years in people with mean BMI of 22.2 (95% CI: 21.9-22.7 kg/m2 ). The HRs (95% CI) for T2D were 1.14 (1.05-1.23) per 10 mmHg systolic blood pressure, 1.05 (1.03-1.08) per 1 cm waist circumference, 1.40 (1.13-1.73) per 1 mmol/L fasting blood glucose, 1.77 (1.15-2.71) per sleeping time (<6 h/day vs 6-7 h/day) and 2.12 (1.25-3.61) per residence (urban vs rural). The prediction nomogram for new-onset T2D had a good discrimination (area under curve: 0.711, 95% CI: 0.666-0.755) and fit calibration (mean absolute error: 0.009). For the predicted probability thresholds between 0.03 and 0.36, the nomogram showed a positive net benefit, without increasing the number of false positives. CONCLUSION: This study highlighted an alarmingly high incidence of T2D in a middle-aged population with a normal range BMI in Vietnam. The individual prediction nomogram with decision curve analysis for new-onset T2D would be valuable for early detection, intervention and treatment of the condition.
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Índice de Masa Corporal , Diabetes Mellitus Tipo 2/epidemiología , Nomogramas , Vigilancia de la Población , Adulto , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Factores de Riesgo , Factores de Tiempo , Vietnam/epidemiologíaRESUMEN
The spike protein (S) of porcine epidemic diarrhea virus (PEDV), in particular, the C-terminal domain of the S1 subunit (S1-CTD), which contains the conserved CO-26K-equivalent (COE) region (aa 499-638), which is recognized by neutralizing antibodies, exhibits a high degree of genetic and antigenic diversity. We analyzed 61 PEDV S1-CTD sequences (630 nt), including 26 from samples collected from seven provinces in northern Vietnam from 2018 to 2019 and 35 other sequences, representing the G1a and 1b, G2a and 2b, and recombinant (G1c) genotypes and vaccines. The majority (73.1%) of the strains (19/26) belonged to subgroup G2b. In a phylogenetic analysis, seven strains were clustered into an independent, distinct subgenogroup named dsG with strong nodal support (98%), separate from both G1a and G1b as well as G2a, 2b, and G1c. Sequence analysis revealed distinct changes (513T>S, 520G>D, 527V>(L/M), 591L>F, 669A>(S/P), and 691V>I) in the COE and S1D regions that were only identified in these Vietnamese strains. This cluster is a new antigenic variant subgroup, and further studies are required to investigate the antigenicity of these variants. The results of this study demonstrated the continuous evolution in the S1 region of Vietnamese PEDV strains, which emphasizes the need for frequent updates of vaccines for effective protection.
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Infecciones por Coronavirus , Virus de la Diarrea Epidémica Porcina , Enfermedades de los Porcinos , Animales , Anticuerpos Neutralizantes , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/veterinaria , Filogenia , Glicoproteína de la Espiga del Coronavirus/genética , Porcinos , Vietnam/epidemiologíaRESUMEN
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.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Diabetes Mellitus Tipo 2 , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Estudios ProspectivosRESUMEN
OBJECTIVES: In this study, the gut microbiome of healthy adult honeybees, Apis cerana, was investigated by sequencing the V3 - V4 region in 16S rRNA gene using Illumina Miseq platform. RESULTS: The total of 37,853 reads for 16S rRNA gene were obtained and 30,121 (79.6%) reads were valid with 25,291 (84.0%) reads that were classified into 116 species belonging to four major phyla. The relative abundances of the bacterial isolates in honeybee samples were phylum Proteobacteria (70.7%), Actinobacteria (10.7%), Firmicutes (10.3%), and Bacteroidetes (8.4%), respectively. Lactic acid bacteria comprised 18.95% with 10 groups including Bifidobacterium asteroides, B. indicum, Fructobacillus fructosus, Lactobacillus apinorum, L. apis, L. helsingborgensis, L. kimbladii, L. kullabergensis, and L. kunkeei. CONCLUSIONS: The presence of beneficial bacteria in the gut highlighted their role in the honeybee and suggested that they can be promising candidates for the development of probiotics for health improvement, infection control and disease management of honeybees.
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Bacterias/clasificación , Abejas/microbiología , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN/métodos , Animales , Bacterias/genética , Bacterias/aislamiento & purificación , ADN Bacteriano/genética , ADN Ribosómico/genética , Microbioma Gastrointestinal , Secuenciación de Nucleótidos de Alto Rendimiento , Filogenia , VietnamRESUMEN
Cholinesterases (ChEs) are enzymes that break down neurotransmitters associated with cognitive function and memory. We isolated cinnamic acids (1 and 2), indolinones (3 and 4), and cycloartane triterpenoid derivatives (5-19) from the roots of Cimicifuga dahurica (Turcz.) Maxim. by chromatography. These compounds were evaluated for their inhibitory activity toward ChEs. Compound 1 was determined to have an IC50 value of 16.7 ± 1.9 µM, and to act as a competitive inhibitor of acetylcholinesterase (AChE). Compounds 3, 4 and 14 were found to be noncompetitive with IC50 values of 13.8 ± 1.5 and 6.5 ± 2.5 µM, and competitive with an IC50 value of 22.6 ± 0.4 µM, respectively, against butyrylcholinesterase (BuChE). Our molecular simulation suggested each key amino acid, Tyr337 of AChE and Asn228 of BuChE, which were corresponded with potential inhibitors 1, and 3 and 4, respectively. Compounds 1 and 4 were revealed to be promising compounds for inhibition of AChEs and BuChEs, respectively.
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Acetilcolinesterasa/metabolismo , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Cimicifuga/química , Simulación del Acoplamiento Molecular , Raíces de Plantas/química , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/aislamiento & purificación , Simulación por Computador , Técnicas In Vitro , Estructura MolecularRESUMEN
This study was designed to search for novel anti-cancer compounds from natural plants. The 70% ethanolic extract from the rizhomes of Cimicifuga dahurica (Turcz.) Maxim. (Ranunculaceae) was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells. A phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of one new phenolic amide glycoside 3, two new lignan glycosides 4 and 7, one new 9,19-cycloartane triterpenoid glycoside 6, and thirteen known constituents 1, 2, 5, and 8â»17. The structures of 3, 4, 6, and 7 were established using contemporary NMR methods and from their HRESIMS data. The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit. Five among the 17 isolated compounds showed significant anti-proliferative effects (p ≤ 0.05), wherein compound 7 showed the most significant anti-proliferative and cell cycle arresting effect (p ≤ 0.05) which followed a dose dependent manner. Western blot protein expression analysis showed a down expression of c-Myc and cyclin D1 which further elucidated the anti-proliferation mechanism of compound 7 while apoptotic effects were found in association with Bcl-2 family protein expression variations. Conclusively this study reports the isolation and identification of 17 compounds from C. dahurica, including four novel molecules, in addition to the fact that compound 7 possesses significant anti-proliferative and apoptotic effects in vitro that may require further exploration.
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Neoplasias de la Mama/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Cimicifuga/química , Extractos Vegetales/farmacología , Neoplasias de la Mama/patología , Femenino , Humanos , Lignanos/química , Células MCF-7 , Fenoles/química , Extractos Vegetales/químicaRESUMEN
The aim of this study was to search for potential therapeutic agents by identifying novel inhibitors of soluble epoxide hydrolase (sEH) from natural plants using an in silico approach. We found that an ethanolic extract from the roots of Cimicifuga dahurica (Turcz.) Maxim. significantly inhibited sEH in vitro. In a phytochemical investigation using assay-guided fractionation of the dichloromethane extract of C. dahurica, we isolated two new indolinone alkaloids (5 and 6) and five related constituents (1-4, and 7) and established their structures based on an extensive analysis using 1D and 2D NMR, and MS methods. All of the isolated compounds inhibited sEH enzymatic activity in a dose-dependent manner, with IC50 values ranging from 0.8±0.0 to 2.8±0.4µM. A kinetic analysis of compounds 1-7 revealed that compound 2 was non-competitive; 1, 3, and 7 were mixed-type; and 4-6 were competitive inhibitors. Molecular docking was employed to further elucidate their receptor-ligand binding characteristics. These results demonstrated that compounds from C. dahurica are potential sEH inhibitors.
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Alcaloides/química , Alcaloides/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Epóxido Hidrolasas/antagonistas & inhibidores , Fenoles/química , Fenoles/farmacología , Cimicifuga/química , Descubrimiento de Drogas , Epóxido Hidrolasas/metabolismo , Humanos , Indoles/química , Indoles/farmacología , Simulación del Acoplamiento Molecular , SolubilidadRESUMEN
A phytochemical assay-guided fractionation of the 95% ethanol extract of Cimicifuga dahurica roots afforded 29 9,19-cycloartane triterpenoid glycosides, including the new cimiricasides A-F (1-6). The structures of 1-6 were established using contemporary NMR methods and from the HRESIMS data, and the sugar moiety in each case was confirmed by acid hydrolysis and subsequent GC/MS analysis. Compounds 2, 4, 5, 7-9, 18, 25, and 29 showed soluble epoxide hydrolase inhibitory effects with IC50 values of 0.4 ± 0.1 to 24.0 ± 0.2 µM. The compounds were analyzed by enzyme kinetic studies to explore the binding mode between the ligand and receptor. Compounds 4 (mixed type), 8, 18, and 29 (noncompetitive type) bound to a preferred allosteric site, while compounds 2, 5, 7, 9, and 25 had competitive interactions at the active site. The binding mechanism of selected inhibitors was investigated using molecular docking and dynamics simulations.
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Cimicifuga/química , Epóxido Hidrolasas/efectos de los fármacos , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Raíces de Plantas/química , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Cromatografía de Gases y Espectrometría de Masas , Glicósidos/química , Simulación del Acoplamiento Molecular , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , República de Corea , Triterpenos/químicaRESUMEN
Sacbrood virus (SBV) is one of the most common viral infections of honeybees. The entire genome sequence for nine SBV infecting honeybees, Apis cerana and Apis mellifera, in Vietnam, namely AcSBV-Viet1, AcSBV-Viet2, AcSBV-Viet3, AmSBV-Viet4, AcSBV-Viet5, AmSBV-Viet6, AcSBV-Viet7, AcSBV-Viet8, and AcSBV-Viet9, was determined. These sequences were aligned with seven previously reported complete genome sequences of SBV from other countries, and various genomic regions were compared. The Vietnamese SBVs (VN-SBVs) shared 91-99% identity with each other, and shared 89-94% identity with strains from other countries. The open reading frames (ORFs) of the VN-SBV genomes differed greatly from those of SBVs from other countries, especially in their VP1 sequences. The AmSBV-Viet6 and AcSBV-Viet9 genome encodes 17 more amino acids within this region than the other VN-SBVs. In a phylogenetic analysis, the strains AmSBV-Viet4, AcSBV-Viet2, and AcSBV-Viet3 were clustered in group with AmSBV-UK, AmSBV-Kor21, and AmSBV-Kor19 strains. Whereas, the strains AmSBV-Viet6 and AcSBV-Viet7 clustered separately with the AcSBV strains from Korea and AcSBV-VietSBM2. And the strains AcSBV-Viet8, AcSBV-Viet1, AcSBV-Viet5, and AcSBV-Viet9 clustered with the AcSBV-India, AcSBV-Kor and AcSBV-VietSBM2. In a Simplot graph, the VN-SBVs diverged stronger in their ORF regions than in their 5' or 3' untranslated regions. The VN-SBVs possess genetic characteristics which are more similar to the Asian AcSBV strains than to AmSBV-UK strain. Taken together, our data indicate that host specificity, geographic distance, and viral cross-infections between different bee species may explain the genetic diversity among the VN-SBVs in A. cerana and A. mellifera and other SBV strains.
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Abejas/virología , Virus ARN/genética , Secuencia de Aminoácidos , Animales , Variación Genética , Genoma Viral , Filogenia , VietnamRESUMEN
Chemical investigation of Acanthopanax koreanum leaves resulted in the isolation of 13 compounds (1-13), including six new (20,29)-dehydrolupane-type triterpenoids: 3α,11α,30-trihydroxylup-20(29)-en-23,28-dioic acid (1), 3α,11α,30-trihydroxylup-20(29)-en-28-oic acid (2), 3α,11α,30-trihydroxylup-23-al-20(29)-en-28-oic acid (3), 3α, 11α-dihydroxy-20-oxo-30-norlupane-23,28-dioic acid (5), (20S)-3α-hydroxy-30 oxolupane-23,28-dioic acid (8), (20S)-3ß,7ß,29-trihydroxy-lupane-23-al-28-oic acid (10), and one novel compound isolated for the first time, named 3α,20α,29-trihydroxylupane-23,28-dioic acid (9), together with six known compounds (4, 6, 7, and 11-13). Chemical structures of the isolated compounds were evaluated by analyzing and comparing spectroscopic data with those reported in the literature. These compounds were also evaluated for their tyrosinase inhibitory effects. Among them, compounds 3, 7, 9, and 12 showed significant inhibitory effects, with inhibitory concentrations of 50% (IC50) values ranging from 8.61 to 63.5 µM.
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Eleutherococcus/química , Inhibidores Enzimáticos/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Extractos Vegetales/química , Triterpenos/química , Eleutherococcus/metabolismo , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/metabolismo , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Conformación Molecular , Monofenol Monooxigenasa/metabolismo , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Unión Proteica , Triterpenos/aislamiento & purificación , Triterpenos/metabolismoRESUMEN
In the search for plants, containing compounds with α-glucosidase inhibitory activity, we found that a methanolic extract from the leaves and twigs of Archidendron clypearia (Jack.) Nielsen significantly inhibited rat intestinal sucrase in vitro. A phytochemical investigation of the aqueous layer of an A. clypearia extract led to the isolation of 14 compounds (1-14). Their structures were established through extensive 1D and 2D NMR, CD data, and MS analysis. The methanolic extract, as well as the water layer at a concentration of 3.0mg/mL, showed potent sucrase inhibitory activity, with 67.78±2.53% and 95.33±2.15% inhibition, respectively. In addition, compounds 6, 7, and 10 (1.0mM) showed potent sucrase inhibition (88.36±1.15%, 81.57±1.07%, and 66.32±4.73% inhibition, respectively), which was comparable to that of the positive control, acarbose, which exhibited 89.54±0.91% inhibition. Other compounds showed moderate or weak inhibitory activity at the same concentration. The sucrase inhibitory activity of the extracts and purified compounds may provide a novel opportunity to develop a new class of antidiabetic agents.
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Fabaceae/química , Intestinos/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Sacarasa/antagonistas & inhibidores , Animales , Dicroismo Circular , Espectroscopía de Resonancia Magnética , Estructura Molecular , Hojas de la Planta/química , Tallos de la Planta/química , RatasRESUMEN
In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, we found that the methanolic extract of the leaves and twigs of Archidendron clypearia (Jack.) Nielsen (Fabaceae) significantly inhibits sEH in vitro. In a phytochemical investigation of the water layer of A. clypearia, we isolated two new chalcones, clypesides A-B (1-2), 13 flavonoid derivatives (3-15) and established their structures based on an extensive 1D and 2D NMR, CD data, and MS analysis. All of the flavonoid derivatives inhibited sEH enzymatic activity in a dose-dependent manner, with IC50 values ranging from 10.0±0.4 to 30.1±2.1µM. A kinetic analysis of compounds 4, 8-10, 12, 13, and 15 revealed that the compounds 8-10 were non-competitive, 4, 13, and 15 were mixed-type, and 12 was competitive inhibitors. Additionally, molecular docking increased our understanding of their receptor-ligand binding. These results demonstrated that flavonoid derivatives from A. clypearia are potential sEH inhibitors.
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Fabaceae/química , Flavonoides/química , Hojas de la Planta/química , Dicroismo Circular , Epóxido Hidrolasas/antagonistas & inhibidores , Flavonoides/farmacología , Cinética , Espectroscopía de Resonancia Magnética , Simulación del Acoplamiento Molecular , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Four new compounds, acacetin 8-C-[ß-D-apiofuranosyl-(1 â 2)-ß-D-glucopyranoside] (1), 7-methoxyacacetin 8-C-[ß-D-apiofuranosyl-(1 â 3)-ß-D-glucopyranoside] (2), 7-methoxyacacetin 8-C-[ß-D-glucopyranosyl-(1 â 2)-ß-D-glucopyranoside] (3), and 4â´-O-acetylacacetin 8-C-[α-L-rhamnopyranosyl-(1 â 2)-ß-D-glucopyranoside] (4), along with ten known compounds (5-14), were isolated from Piper aduncum leaves. The effects of these compounds on lipopolysaccharide-induced expression of the proinflammatory cytokines IL-12 p40, IL-6, and TNF-α in bone marrow-derived dendritic cells were evaluated. Compounds 2, 3, 6, 8, 9, and 11-13 inhibited the production of both IL-12 p40 and IL-6, with IC50 values ranging from 0.35 ± 0.01 to 1.40 ± 0.04 µM and 1.22 ± 0.02 to 3.79 ± 0.10 µM, respectively. Compounds 5 and 10 only showed strong inhibition effects on the production of IL-12 p40, with IC50 values of 2.76 ± 0.08 and 0.39 ± 0.05 µM, respectively. However, all compounds showed weak activity or no activity on TNF-α production at the tested concentrations.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Flavonoides/química , Flavonoides/farmacología , Piper/química , Animales , Antiinflamatorios no Esteroideos/química , Citocinas/metabolismo , Células Dendríticas/efectos de los fármacos , Evaluación Preclínica de Medicamentos/métodos , Flavonoides/aislamiento & purificación , Glicósidos/química , Glicósidos/farmacología , Concentración 50 Inhibidora , Lipopolisacáridos/farmacología , Espectroscopía de Resonancia Magnética , Ratones Endogámicos C57BL , Estructura Molecular , Extractos Vegetales/farmacología , Hojas de la Planta/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Non-small cell lung cancer (NSCLC) is the major cancer-related death worldwide with only 14% five-year survival rate. Triticumoside, a phenolic compound present in Triticum aestivum sprout extract, has been recognized to have antiobesity and anti-inflammatory effects. However, the effect of triticumoside on cancer cell proliferation and migration has not been studied. In order to elucidate whether triticumoside exhibits an anticancer effect, cells were incubated with different doses of triticumoside, and apoptosis was assessed by observing cell viability, cellular morphological changes, and annexin-V-fluorescein isothiocyanate/propidium iodide staining. Cell cycle analysis, western blotting, wound healing assay, and quantitative-polymerase chain reaction were also performed. Triticumoside exhibited marked cytotoxicity in the cells in dose- and time-dependent manner. Triticumoside caused morphological changes, including cellular rounding, nuclear condensation, and shrinkage. Likewise, triticumoside enhanced the sub-G1 proportion of cells. Additionally, triticumoside regulated expression of apoptosis-associated proteins, such as B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X, and procaspase-3/9. Triticumoside also inhibited migration of the cells through downregulation of matrix metalloproteinase-2/9 (MMP2/9). Collectively, these results suggest that triticumoside induces apoptosis through caspase-dependent mitochondrial pathway and suppresses migration via inhibition of MMP2/9 in NSCLC A549 cells.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Caspasas/metabolismo , Flavonas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Fenoles/farmacología , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Flavonas/química , Células HEK293 , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/patología , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fenoles/química , Transducción de Señal/efectos de los fármacos , Triticum/químicaRESUMEN
CONTEXT: Nepenthes mirabilis (Lour.) Rafarin (Nepenthaceae) is a carnivorous plant used as a folk medicine in the treatment of jaundice, hepatitis, gastric ulcers, ureteral stones, diarrhea, diabetes, and high blood pressure. Neither the phytochemical content nor biological activities of N. mirabilis have been reported. OBJECTIVE: The anti-inflammatory activity from the N. mirabilis methanolic extract led to the isolation of compounds (1-26). MATERIALS AND METHODS: Chromatographic methods were used to isolate compounds from the methanol extract of N. mirabilis branches and leaves. The anti-inflammatory activity of these isolated compounds was investigated in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) using ELISA. Primary BMDCs were used to examine the production of pro-inflammatory cytokines (IL-12 p40, IL-6, and TNF-α, at concentrations of 0.1, 0.2, and 1.0 µM) as compared with a positive control, SB203580 (1.0 µM). MTT assays showed that isolated compounds (1-26) did not exhibit significant cytotoxicity at concentrations up to 20.0 µM. RESULTS: Compound 9 showed potent inhibition of IL-12 p40, IL-6, and TNF-α production (IC50 = 0.17 ± 0.02, 0.46 ± 0.01, and 8.28 ± 0.21 µM, respectively). Compound 4 showed potent inhibition of IL-12 p40 and IL-6 production (IC50 = 1.17 ± 0.01 and 2.15 ± 0.04 µM). In addition, IL-12 p40 inhibition by naphthalene derivatives (1-7, 9, and 10), phenolic compounds (11-15), lupeone (18), and flavonoids (22, 25, and 26) was more potent than with the positive control. The isolated compounds exhibited little and/or no inhibitory effects on TNF-α production in LPS-stimulated BMDCs. DISCUSSION AND CONCLUSION: Taken together, these data suggest that the isolated components have significant inhibitory effects on pro-inflammatory cytokine production and warrant further study concerning their potential medicinal use.