RESUMEN
This work offered a productive technique for resveratrol extraction from Polygonum Cuspidatum (P. Cuspidatum) using ionic liquids in synergy with ultrasound-enzyme-assisted extraction (UEAE). Firstly, ionic liquids with different carbon chains and anions were evaluated. Subsequently, a comprehensive investigation was carried out to evaluate the effect of seven crucial parameters on the resveratrol yield: pH value, enzyme concentration, extraction temperature, extraction time, ultrasonic power, concentration of ionic liquid (IL concentration) and the liquid-solid ratio. Employing the Plackett-Burman Design (PBD), the critical factors were effectively identified. Building upon this foundation, the process was further optimized through the application of Response Surface Methodology (RSM) and an Artificial Neural Network-Genetic Algorithm (ANN-GA). The following criteria were determined to be the ideal extraction conditions: an enzyme concentration of 2.18%, extraction temperature of 58 °C, a liquid-solid ratio of 29 mL/g, pH value of 5.5, extraction time of 30 min, ultrasonic power of 250 W, and extraction solvent of 0.5 mol/L 1-butyl-3-methylimidazolium bromide. Under these conditions, the resveratrol yield was determined to be 2.90 ± 0.15 mg/g. Comparative analysis revealed that the ANN-GA model provided a better fit to the experimental data of resveratrol yield than the RSM model, suggesting superior predictive capabilities of the ANN-GA approach. The introduction of a novel green solvent system in this experiment not only simplifies the extraction process but also enhances safety and feasibility. This research paves the way for innovative approaches to extracting resveratrol from botanical sources, showcasing its significant potential for a wide range of applications.
Asunto(s)
Fraccionamiento Químico , Fallopia japonica , Líquidos Iónicos , Resveratrol , Resveratrol/aislamiento & purificación , Resveratrol/química , Líquidos Iónicos/química , Fallopia japonica/química , Fraccionamiento Químico/métodos , Temperatura , Ondas Ultrasónicas , Concentración de Iones de Hidrógeno , Estilbenos/aislamiento & purificación , Estilbenos/química , Enzimas/metabolismoRESUMEN
A novel magnetic nanocomposite of chitosan-grafted-poly(N-vinylcaprolactam) (Fe3O4/SiO2/CHT-g-PNVCL MNC) were synthesized. Chitosan was prepared from shrimp shells Penaeus monodon by a green deacetylation approach. N-vinylcaprolactam was first polymerized on the surface of Fe3O4 magnetic nanoparticles using surface-initiated atom transfer radical polymerization. Then, the Fe3O4 nanoparticles modified with carboxyl-terminated- poly(N-vinylcaprolactam) was grafted onto chitosan. Various techniques were used to characterize of physicochemical properties of synthesized nanomaterials. The application of Fe3O4/SiO2/CHT-g-PNVCL MNC was utilized as a novel adsorbent for the simultaneous extraction of trans-resveratrol and its major phase II metabolites from rat plasma. A qualitative analysis was performed using ultra-performance liquid chromatography triple-quadrupole tandem mass spectrometry. Response surface methodology based on central composite design was used to optimize the extraction procedure including pH, amount of adsorbent, extraction time, desorption time, and volume of elution solvent. The established quantitative method succeeded in satisfying FDA requirements regarding biological analysis methods. The results of the validation of the method indicated its acceptable accuracy (-4.4 to 6.9%), linearity (r > 0.995), precision (CV < 6.3%), and stability. The lower limits of quantification of the proposed method achieved were 1.23-1.68 ngmL-1for target analytes. The information obtained from the method validation has been used to estimate the expanded uncertainty for the determination of trans-resveratrol in rat plasma samples following orally administered trans-resveratrol. The method was applied to study the pharmacokinetics, metabolism, and bioavailability of trans-resveratrol in healthy rats following a single oral or intravenous dose.
Asunto(s)
Nanopartículas de Magnetita/química , Resveratrol , Microextracción en Fase Sólida/métodos , Animales , Caprolactama/análogos & derivados , Quitosano/química , Cromatografía Líquida de Alta Presión , Límite de Detección , Modelos Lineales , Nanocompuestos/química , Polímeros , Ratas , Reproducibilidad de los Resultados , Resveratrol/sangre , Resveratrol/aislamiento & purificación , Dióxido de Silicio/química , Espectrometría de Masas en TándemRESUMEN
The bioassay-guided fractionation of a CHCl3-MeOH extract from the stems of Cissus trifoliata identified an active fraction against PC3 prostate cancer cells. The treatment for 24 h showed an 80% reduction in cell viability (p ≤ 0.05) by a WST-1 assay at a concentration of 100 µg/mL. The HPLC-QTOF-MS analysis of the fraction showed the presence of coumaric and isoferulic acids, apigenin, kaempferol, chrysoeriol, naringenin, ursolic and betulinic acids, hexadecadienoic and octadecadienoic fatty acids, and the stilbene resveratrol. The exposure of PC3 cells to resveratrol (IC25 = 23 µg/mL) for 24 h induced significant changes in 847 genes (Z-score ≥ ±2). The functional classification tool of the DAVID v6.8 platform indicates that the underlying molecular mechanisms against the proliferation of PC3 cells were associated (p ≤ 0.05) with the process of differentiation and metabolism. These findings provide experimental evidence suggesting the potential of C. trifoliata as a promising natural source of anticancer compounds.
Asunto(s)
Antineoplásicos Fitogénicos/química , Proliferación Celular/efectos de los fármacos , Cissus/química , Proteínas de Neoplasias/genética , Transcriptoma , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Apigenina/química , Apigenina/aislamiento & purificación , Apigenina/farmacología , Bioensayo , Supervivencia Celular/efectos de los fármacos , Flavanonas/química , Flavanonas/aislamiento & purificación , Flavanonas/farmacología , Flavonas/química , Flavonas/aislamiento & purificación , Flavonas/farmacología , Perfilación de la Expresión Génica , Humanos , Quempferoles/química , Quempferoles/aislamiento & purificación , Quempferoles/farmacología , Masculino , Análisis por Micromatrices , Proteínas de Neoplasias/clasificación , Proteínas de Neoplasias/metabolismo , Células PC-3 , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/aislamiento & purificación , Triterpenos Pentacíclicos/farmacología , Extractos Vegetales/química , Resveratrol/química , Resveratrol/aislamiento & purificación , Resveratrol/farmacología , Ácido BetulínicoRESUMEN
Polyphenolic enriched extracts from two species of Cyperus, Cyperus glomeratus and Cyperus thunbergii, possess mammalian arginase inhibitory capacities, with the percentage inhibition ranging from 80% to 95% at 100 µg/mL and 40% to 64% at 10 µg/mL. Phytochemical investigation of these species led to the isolation and identification of two new natural stilbene oligomers named thunbergin A-B (1-2), together with three other stilbenes, trans-resveratrol (3), trans-scirpusin A (4), trans-cyperusphenol A (6), and two flavonoids, aureusidin (5) and luteolin (7), which were isolated for the first time from C.thunbergii and C. glomeratus. Structures were established on the basis of the spectroscopic data from MS and NMR experiments. The arginase inhibitory activity of compounds 1-7 was evaluated through an in vitro arginase inhibitory assay using purified liver bovine arginase. As a result, five compounds (1, 4-7) showed significant inhibition of arginase, with IC50 values between 17.6 and 60.6 µM, in the range of those of the natural arginase inhibitor piceatannol (12.6 µM). In addition, methanolic extract from Cyperus thunbergii exhibited an endothelium and NO-dependent vasorelaxant effect on thoracic aortic rings from rats and improved endothelial dysfunction in an adjuvant-induced arthritis rat model.
Asunto(s)
Arginasa/antagonistas & inhibidores , Cyperus/química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Animales , Aorta Torácica/efectos de los fármacos , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/fisiopatología , Benzofuranos/química , Benzofuranos/aislamiento & purificación , Benzofuranos/farmacología , Calamus , Bovinos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Inhibidores Enzimáticos/aislamiento & purificación , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Masculino , Metanol , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas , Resveratrol/química , Resveratrol/aislamiento & purificación , Resveratrol/farmacología , Estilbenos/química , Estilbenos/aislamiento & purificación , Estilbenos/farmacología , Vasodilatadores/química , Vasodilatadores/aislamiento & purificación , Vasodilatadores/farmacologíaRESUMEN
Rheum ribes L. (Rhubarb) is one of the most important edible medicinal plants in the Eastern Anatolia region and is called "Iskin" by local people. Resveratrol and 6-O-methylalaternin were isolated from the Rhubarb for the first time in addition to well-known secondary metabolites including emodin, aloe-emodin, ß-sitosterol and rutin. The new semi-synthetic anthraquinone derivatives with the NαFmoc-l-Lys and ethynyl group were synthesized from the isolated anthraquinones emodin and aloe-emodin of Rhubarb to increase the bioactivities. Aloe-emodin derivative with NαFmoc-l-Lys shows the highest inhibition values by 94.11 ± 0.12 and 82.38 ± 0.00% against HT-29 and HeLa cell lines, respectively, at 25 µg/mL. Further, modification of the aloe-emodin with both the ethynyl and the NαFmoc-l-Lys groups showed an antioxidant activity-enhancing effect. From molecular docking studies, the relative binding energies of the emodin and aloe-emodin derivatives to human serum albumin ranged from -7.30 and -10.62 kcal/mol.
Asunto(s)
Antraquinonas/química , Antineoplásicos/síntesis química , Resveratrol/química , Rheum/química , Antraquinonas/síntesis química , Antraquinonas/aislamiento & purificación , Antraquinonas/metabolismo , Antraquinonas/farmacología , Antineoplásicos/farmacología , Sitios de Unión , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Emodina/química , Emodina/aislamiento & purificación , Emodina/metabolismo , Emodina/farmacología , Humanos , Simulación del Acoplamiento Molecular , Componentes Aéreos de las Plantas/química , Componentes Aéreos de las Plantas/metabolismo , Resveratrol/aislamiento & purificación , Resveratrol/farmacología , Rheum/metabolismo , Albúmina Sérica/química , Albúmina Sérica/metabolismoRESUMEN
A novel resveratrol molecularly imprinted polymer (p-CM@MPS@MIP-Res) was prepared on the surface of silanized porous cellulose microspheres (p-CM@MPS) for the first time, and was successfully applied for the efficient enrichment of targeted resveratrol in Polygonum cuspidatum. The adsorption kinetics and adsorption equilibrium of p-CM@MPS@MIP-Res were also studied in detail. Compared with non-molecularly imprinted polymer (p-CM@MPS@NIP), the prepared p-CM@MPS@MIP-Res showed high adsorption capacity for resveratrol, the adsorption capacity of the p-CM@MPS@MIP-Res could reach to 11.56 mg/g. Furthermore, the stability of the p-CM@MPS@MIP-Res was evaluated and the result showed that the p-CM@MPS@MIP-Res could be reused for 5 runs. Finally, the p-CM@MPS@MIP-Res was applied to enrich the resveratrol in Polygonum cuspidatum sample, the content of resveratrol in the extraction solution could be increased greatly from 4.23 % to 23.74 %, indicating the p-CM@MPS@MIP-Res was a promising adsorbent for efficiently separation and enrichment of resveratrol in Polygonum cuspidatum.
Asunto(s)
Celulosa/química , Microesferas , Polímeros Impresos Molecularmente/química , Resveratrol/aislamiento & purificación , Adsorción , Fraccionamiento Químico , Cromatografía Líquida de Alta Presión/métodos , Fallopia japonica/química , Cinética , Impresión Molecular , Polímeros/química , Porosidad , Resveratrol/análisisRESUMEN
The discovery of melatonin (Mel) in wines triggered a new interest in the paradigm of health benefits and wine consumption, usually ascribed to trans-resveratrol (trans-RSV). In this context, a dispersive liquid-liquid microextraction for the analysis of Mel and trans-RSV in wines by LC-FLD was developed. A 26-1 factorial design was used to identify the significant variables (p < 0.05) and Central Composite Design was used to achieve the optimal conditions: 300 µL of chloroform (extracting solvent), 1500 µL of acetonitrile (disperser solvent) and 1500 mg of NaCl (ionic strength). Excellent linearity (R2 > 0.9999), repeatability (<3.55%), and accuracy (<7.18%) were obtained using a blank matrix and recoveries (>91.9%) using wines. The method was successfully applied to the analyses of Mel (0.63-7.44 ng mL-1) and trans-RSV (169-2616 ng mL-1) in different wine varieties. Comparison with literature point the overall advantages of the new method.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Análisis de los Alimentos/métodos , Microextracción en Fase Líquida/métodos , Melatonina/análisis , Resveratrol/análisis , Vino/análisis , Melatonina/aislamiento & purificación , Concentración Osmolar , Resveratrol/aislamiento & purificación , Solventes/química , Factores de TiempoRESUMEN
The current study develops an effective, convenient, low-cost, and environmentally friendly method for determining trans-resveratrol (TRA) in peanut oils, the unique proportion of peanut oil, by employing natural cotton fibers without any pretreatment as extraction sorbent and an in-syringe extraction device. The primary factors affecting the extraction recovery are optimized in detail. The condition of 200.0 mg of cotton fibers, six push-pull times, 2.0 mL of n-hexane as washing solvent and 2.0 mL of ethanol as desorption solvent is selected as the best. The linear range is demonstrated to be 10-1000 ng/g with a satisfactory correlation coefficient (R2 = 0.9995), while the limit of detection is calculated as 2.47 ng/g. In addition, the recoveries of TRA are obtained in the range of 93.8-104.4% with RSDs less than 5.5%. Finally, the developed method is successfully applied to determine TRA concentrations in commercial peanut oils and other edible oils.
Asunto(s)
Arachis/química , Cromatografía Líquida de Alta Presión/métodos , Fibra de Algodón , Aceite de Cacahuete/química , Resveratrol/análisis , Adsorción , Arachis/metabolismo , Hexanos/química , Isomerismo , Límite de Detección , Reproducibilidad de los Resultados , Resveratrol/aislamiento & purificación , Extracción en Fase Sólida/instrumentación , Extracción en Fase Sólida/métodos , Espectrofotometría UltravioletaRESUMEN
Cancer cells meet their energy need by predominantly increased uptake of glucose, high rate of glycolysis, and increased production of lactate even in the presence of adequate oxygen. This process was proposed by Otto Warburg and named after him as the Warburg effect. The development of drugs that target glucose intake and aerobic glycolysis or lactic acid secretion of cancer cells is a newer approach for drug discovery. We have tested five purified plants-derived compounds such as curcumin, quercetin, ellagic acid, resveratrol, and indole-3-carbinol in HeLa cells for cytotoxicity, inhibition of metastasis, and modulation of lactate-pyruvate metabolism. Standard biochemical methods were used for glucose, lactic acid, and pyruvic acid measurement. The cell viability was determined by MTT assay. Cell migration was checked by wound healing assay. A dose-dependent cytotoxic effect and inhibition of cell migration were observed in all the tested compounds. A decrease in the lactate and increase in pyruvate level was observed in all the tested compounds except ellagic acid. Our finding suggests that tested phytocompounds are associated with the metabolic reprogramming of cancer cells and execute the cytotoxic effect. These compounds could be used for cancer prevention and therapy.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Curcumina/farmacología , Indoles/farmacología , Ácido Láctico/antagonistas & inhibidores , Ácido Pirúvico/metabolismo , Quercetina/farmacología , Resveratrol/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Curcumina/química , Curcumina/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Indoles/química , Indoles/aislamiento & purificación , Ácido Láctico/análisis , Ácido Láctico/metabolismo , Ácido Pirúvico/análisis , Quercetina/química , Quercetina/aislamiento & purificación , Resveratrol/química , Resveratrol/aislamiento & purificación , Células Tumorales CultivadasRESUMEN
The present study aimed to screen grape extracts as novel α-glucosidase inhibitors to prevent type-2 diabetes and hyperglycemia. The total polyphenol content (TPC) was measured by Folin-Ciocalteu assay and the stilbene, anthocyanin and flavan-3-ol compounds were measured by Ultra High-Performance Liquid Chromatography coupled to Mass Spectrometry (UHPLC-MS). The α-glucosidase inhibitory of seed and skin Tannat grape extracts at four ripening stages were investigated. The highest TPC values were measured in seeds at the "veraison stage" (65.29 ± 5.33 g of Gallic Acid Equivalent (GAE) per kilogram of Fresh Weight (FW)). This was in accordance with the high flavan-3-ol contents measured for these two extracts (43.22 ± 2.59 and 45.45 ± 6.48 g/kg of seeds FW, respectively). The skin and seed extracts at the first stage of ripening exerted strong α-glucosidase inhibition, exceeding 95% (p < 0.05). A high linear correlation (R = 0.723, p ≤ 0.05) was observed between flavan-3-ol contents and the α-glucosidase inhibitory activity. The stilbene contents and this activity were moderately to strongly anti-correlated (R = -0.828, p ≤ 0.05 for trans-resveratrol). The enzyme kinetic studies revealed a mixed type of inhibition. This study brings promising results for the therapeutic potential of seed and skin Tannat grape extracts as a functional food product with anti-diabetic activity.
Asunto(s)
Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Extractos Vegetales/química , Polifenoles/aislamiento & purificación , Vitis/química , alfa-Glucosidasas/metabolismo , Antocianinas/química , Antocianinas/aislamiento & purificación , Antocianinas/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Biocatálisis/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Cinética , Espectrometría de Masas , Estructura Molecular , Polifenoles/química , Polifenoles/farmacología , Resveratrol/química , Resveratrol/aislamiento & purificación , Resveratrol/farmacología , Estilbenos/química , Estilbenos/aislamiento & purificación , Estilbenos/farmacología , Vitis/crecimiento & desarrolloRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia suffruticosa Andr. has been widely used in traditional Chinese medicine as an anti-tumour, anti-oxidant, anti-inflammatory and neuroprotective agent. Resveratrol oligomers are the main components of the seed coat extracts of Paeonia suffruticosa (PSCE) and have DPPH free radical scavenging and ß-secretase inhibitory activity. However, studies of its effect on ameliorating cognitive deficits are limited, and analyses of the underlying mechanisms are insufficient. AIM OF STUDY: This study aimed to investigate the cholinesterase inhibitory activities of resveratrol oligomers from P. suffruticosa in vitro and their effects on diminishing the oxygen-glucose deprivation/reoxygenation (OGD/R) -induced cytotoxicity in PC12 cells and scopolamine-induced cognitive deficits in mice. Moreover, the underlying mechanisms were further explored. MATERIALS AND METHODS: In vitro, the inhibitory effects of PSCE and its 10 stilbenes on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated using the Ellman's assay, and its protective effects on normal and OGD/R-injured PC12 cells were evaluated using the MTT assay. For the in vivo assay, C57BL/6 mice were orally administered with PSCE at doses of 150 and 600 mg/kg for 28 days, and injected with scopolamine (1.5 mg/kg) to induce cognitive deficits. The memory behaviours were evaluated using the novel object recognition, Morris water maze and inhibitory avoidance test. Levels of various biochemical markers were also examined, including AChE, choline acetyltransferase (ChAT), acetylcholine (ACh), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) in the mouse brain and interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), interleukin-4 (IL-4) in serum. RESULTS: PSCE and its 10 stilbenes display good inhibition of AChE and BuChE activities and significantly increase the viability of normal and OGD/R-injured PC12 cells. PSCE improves the cognitive performance of scopolamine-treated mice in behavioural tests. Meanwhile, PSCE increases AChE, ChAT, SOD, and CAT activities and ACh, GSH, IL-4 levels, and decreases IL-1ß, IL-6, TNF-α levels in the model animals. CONCLUSIONS: Resveratrol oligomers from P. suffruticosa show neuroprotective effect in vitro and in vivo by regulating cholinergic, antioxidant and anti-inflammatory pathways, may have promising application in the treatment of Alzheimer's disease.
Asunto(s)
Inhibidores de la Colinesterasa/farmacología , Disfunción Cognitiva/prevención & control , Paeonia/química , Resveratrol/farmacología , Acetilcolinesterasa/efectos de los fármacos , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Butirilcolinesterasa/efectos de los fármacos , Inhibidores de la Colinesterasa/aislamiento & purificación , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/farmacología , Células PC12 , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Ratas , Resveratrol/administración & dosificación , Resveratrol/aislamiento & purificación , EscopolaminaRESUMEN
Red wine compounds have been reported to reduce the rate of atherosclerosis by inducing nitric oxide (NO) production and antioxidant enzyme expression in vascular endothelial cells (VECs). The present study compared the effects of the three red wine compounds resveratrol and its dimers, ε-viniferin and δ-viniferin, on VECs function for the first time. Both 5 µM ε-viniferin and δ-viniferin, but not 5 µM resveratrol, significantly stimulated wound repair of VECs. Increased levels of wound repair induced by 10 and 20 µM ε-viniferin were significantly higher than those stimulated by 10 and 20 µM resveratrol, respectively. These stimulatory effects of the three compounds were suppressed by the NO synthase inhibitor L-NAME. When VECs were exposed to each compound, endothelial NO synthase was activated and the expression of sirtuin 1 (SIRT1) and HO-1 was induced. Addition of the SIRT1 and HO-1 inhibitors EX527 and ZnPPiX, respectively, suppressed wound repair stimulated by the three compounds, demonstrating that SIRT1 and HO-1 are involved in these wound repair processes. Furthermore, each compound induced the suppression of H2 O2 -dependent reduction of cell viability as well as the expression of the antioxidant enzyme catalase. These data suggest that not only resveratrol, but also its dimers, ε-viniferin and δ-viniferin, may be effective in preventing atherosclerosis by a similar molecular mechanism with different potency and efficacy.
Asunto(s)
Antioxidantes/farmacología , Benzofuranos/farmacología , Células Endoteliales/efectos de los fármacos , Óxido Nítrico/agonistas , Resorcinoles/farmacología , Resveratrol/farmacología , Estilbenos/farmacología , Vino/análisis , Animales , Antioxidantes/aislamiento & purificación , Aterosclerosis/prevención & control , Benzofuranos/aislamiento & purificación , Carbazoles/farmacología , Catalasa/genética , Catalasa/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Dimerización , Células Endoteliales/citología , Células Endoteliales/enzimología , Inhibidores Enzimáticos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Humanos , NG-Nitroarginina Metil Éster/antagonistas & inhibidores , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Protoporfirinas/farmacología , Resorcinoles/aislamiento & purificación , Resveratrol/aislamiento & purificación , Sirtuina 1/genética , Sirtuina 1/metabolismo , Estilbenos/aislamiento & purificación , PorcinosRESUMEN
Resveratrol, a phytoalexin, is a natural polyphenol synthesized exclusively by plants in response to environmental stresses. However, the molecule has also many exogenous bioactivities in animal cells. These bioactivities may lead to anti-cancer and cardio-protective health benefits. Because cellular responses to the treatment with resveratrol include the changes of expression patterns, functional genomics is an attractive tool to study them. In recent and today's experimental practice, this mostly means microarray profiling of gene expression (using RNAs isolated from bulk tissues). Herein, we review such published studies undertaken in the context of cardiovascular diseases (CVDs). CVDs are a number one public health problem in developed countries, outweighing in magnitude even cancer. In particular, we review the studies of resveratrol in several animal models relevant to CVDs. These models included: normal and pre-mature aging in mice, as well as atherogenic diet in mice / pigs / non-human primates. Additionally, there were few clinical studies published in the context of the comorbidities of atherosclerosis in humans (e.g. obesity, diabetes, hypertension). For the purposes of these studies, three types of samples were most commonly profiled with microarrays: the liver, the skeletal muscle, and peripheral blood mononuclear cells. Resveratrol-induced changes of gene expression typically mimicked those associated with calorie restriction and lifespan extension. They also opposed changes induced by the atherogenic diet. We conclude by discussing few experimental factors that were relatively neglected thus far, but which could be interesting to investigate in the future. These factors include sex and the exact formulation of resveratrol (plant extract, or synthetic chemical).
Asunto(s)
Aterosclerosis/tratamiento farmacológico , Dieta , Suplementos Dietéticos , Genómica , Leucocitos Mononucleares/efectos de los fármacos , Hígado/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Resveratrol/farmacología , Transcriptoma/efectos de los fármacos , Animales , Aterosclerosis/genética , Aterosclerosis/metabolismo , Modelos Animales de Enfermedad , Femenino , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Leucocitos Mononucleares/metabolismo , Hígado/metabolismo , Masculino , Músculo Esquelético/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Resveratrol/síntesis química , Resveratrol/aislamiento & purificación , Especificidad de la EspecieRESUMEN
Resveratrol, a stilbene phytoalexin in plants, is believed to benefit human health. In this study, an optimized enzyme-assisted method was developed to extract the total content of trans-resveratrol (free or combined with glucose) in peanut seeds, followed by detection using high-performance liquid chromatography. The extraction process was optimized by Box-Behnken design and response surface methodology. The optimized enzyme concentration, digestion time, pH, and temperature were 3.02 g/L, 57.06 min, 5.88, and 51.05°C, respectively. Validation tests indicated that the experimental yield of trans-resveratrol was 0.183 ± 0.007 µg/g with a relative standard deviation of 3.87% (n = 5) under the optimal condition, which was closely agreed with the predicted value (0.182 µg/g). The recoveries obtained from the spiked samples were varied from 89.4 to 103.9%. Therefore, this study will provide a useful method for quantification of total trans-resveratrol in peanut seeds.
Asunto(s)
Arachis/química , Resveratrol/aislamiento & purificación , Semillas/química , Celulasa/química , Celulasa/metabolismo , Cromatografía Líquida de Alta Presión , Resveratrol/química , Resveratrol/metabolismo , Propiedades de SuperficieRESUMEN
Resveratrol is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or attack by fungi. The underutilization of soybean seed coat (Glycine max (L.) Merrill.) and tempeh, cheap Indonesia fermented food thus opens up a new opportunity for developing a Resveratrol-based medicine for Plants-Derived Neuroprotective Agents purposes. In this study, it was isolated from tempeh, ordinarily well-known as Indonesian soybean fermented food, and soybean seed coat. The finding of this compound was confirmed by TLC and HPLC analysis applying fluorescence detection. From this, the Rf-value for transresveratrol is 0.64. As eluent, a mixture of chloroform, ethyl acetate, and formic acid (2.5+1+0.1, v/v) was selected. In addition, retention time for tempeh was 14.467 and for soybean seed coat was 11.977. The extraction yield of resveratrol was 65.15 % in tempeh and 55.35 % in soybean seed coat. Resveratrol isolated from Tempeh and Soybean seed coat gave prevents some reaction by modulating intracellular signaling pathways: protein kinase C (PKC), a family of 12 serine/ threonine kinases and providing a new lead molecule for neuroprotective affects in addition to has prevented cell death by apoptosis.
El resveratrol es un estilbenoide, un tipo de fenol natural, y fitoalexina producida por varias plantas en respuesta a una lesión o ataque de hongos. La subutilización de la cubierta de la semilla de soja (Glycine max (L.) Merrill.) y el tempeh, alimento fermentado barato de Indonesia, abren una nueva oportunidad para obtener un medicamento a base de resveratrol para propósitos de desarrollo de agentes neuroprotectores derivados de plantas. En este estudio, se aisló el resveratrol del tempeh, generalmente conocido como alimento fermentado de soja de Indonesia y de la cubierta de la semilla de soja. El hallazgo de este compuesto se confirmó mediante análisis de TLC y HPLC aplicando detección de fluorescencia. A partir de esto, el valor de Rf para trans-resveratrol es 0,64. Como eluyente, se seleccionó una mezcla de cloroformo, acetato de etilo y ácido fórmico (2,5 + 1 + 0,1, v / v). Además, el tiempo de retención para el tempeh fue de 14,467 y para el revestimiento de semilla de soja fue de 11,977. El rendimiento de extracción del resveratrol fue del 65,15 % en tempeh y del 55,35 % en la cubierta de la semilla de soja. El resveratrol aislado de tempeh y de la cubierta de la semilla de soja previno reacciones mediante la modulación de ciertas vías de señalización intracelular: proteína quinasa C (PKC), una familia de 12 serina/treonin quinasas, proporcionando una nueva molécula de plomo con efectos neuroprotectores, además de prevenir la muerte celular por apoptosis.
Asunto(s)
Animales , Ratones , Glycine max/química , Fármacos Neuroprotectores/aislamiento & purificación , Alimentos de Soja/análisis , Resveratrol/aislamiento & purificación , Semillas/química , Células Cultivadas , Cromatografía Líquida de Alta Presión , Cromatografía en Capa DelgadaRESUMEN
As a traditional natural medicine for treating many kinds of diseases, Gnetum parvifolium showed apparent inhibition on xanthine oxidase (XO). In this study, ultrafiltration combined with liquid chromatography-mass spectrometry (LC-MS) is used for the screening of XO inhibitors from Gnetum parvifolium. Their antioxidation, XO inhibition, and enzymic kinetic parameters are also determined. Finally, piceatannol (1), rhaponiticin (2), resveratrol (3), and isorhapontigenin (4) are screened out and identified as XO inhibitors from the extract of Gnetum parvifolium. Four inhibitors show better inhibition than allopurinol and good radical scavenging abilities. However, the antioxidant activities are weaker than ascorbic acid. The kinetic parameters illustrate the inhibition mode of XO by piceatannol is competitive type, while the inhibition modes for rhaponiticin, resveratrol and isorhapontigenin are uncompetitive types. In order to evaluate the difference among samples obtained in China, the amounts of four inhibitors and related activities in 20 samples are assessed and analyzed by partial least squares analysis. The results indicate piceatannol contribute the highest coefficients in three kinds of activities. Based on these findings, more comprehensive research on pharmaceutical and biochemical activities of these four XO inhibitors could be conducted in future.
Asunto(s)
Gnetum/química , Resveratrol/aislamiento & purificación , Estilbenos/aislamiento & purificación , Xantina Oxidasa/antagonistas & inhibidores , Alopurinol/farmacología , Compuestos de Bifenilo/antagonistas & inhibidores , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Depuradores de Radicales Libres/aislamiento & purificación , Depuradores de Radicales Libres/farmacología , Ensayos Analíticos de Alto Rendimiento , Cinética , Análisis de los Mínimos Cuadrados , Picratos/antagonistas & inhibidores , Extractos Vegetales/química , Resveratrol/farmacología , Estilbenos/farmacología , Ultrafiltración , Xantina Oxidasa/metabolismoRESUMEN
It has been suggested that the fruit components resveratrol (RSV), 6', 7'-dihydroxybergamottin (DHB), and bergamottin (BG) might inhibit cytochrome P450 2C19 (CYP2C19) activity, but the mode and potency of such inhibition are yet to be investigated. This study aimed to investigate the mode and kinetics of the inhibition of CYP2C19-based omeprazole metabolism by RSV or grapefruit juice components (DHB or BG). RSV and DHB reduced CYP2C19 activity in a preincubation time-dependent manner, suggesting that they inactivated CYP2C19 via mechanism-based inhibition (MBI). Although BG inactivated CYP2C19 in a preincubation time- and concentration-dependent manner, suggesting that both MBI and reversible inhibition contributed to these effects, the concentration required to achieve 50% inhibition was 26-fold higher for reversible inhibition than for MBI (0.859 and 0.0331 µM, respectively), indicating that the inhibition of CYP2C19 by BG is primarily attributable to MBI. Based on the estimated intestinal concentrations of these components, it is considered that >90% of CYP2C19 would be inactivated after the consumption of normal amounts of grapefruit juice or RSV-containing substances. In conclusion, these findings suggest that food containing these components has the potential to evoke drug-food interactions caused by the MBI of intestinal CYP2C19 activity in the clinical setting.
Asunto(s)
Inhibidores del Citocromo P-450 CYP2C19/farmacología , Citocromo P-450 CYP2C19/metabolismo , Frutas/química , Furocumarinas/farmacología , Resveratrol/farmacología , Citrus paradisi/química , Citocromo P-450 CYP2C19/genética , Inhibidores del Citocromo P-450 CYP2C19/aislamiento & purificación , Interacciones Alimento-Droga , Jugos de Frutas y Vegetales , Furocumarinas/aislamiento & purificación , Humanos , Cinética , Omeprazol/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Resveratrol/aislamiento & purificación , Especificidad por Sustrato , Vitis/química , VinoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Hopea ponga (Dennst.) Mabb. Is used in traditional herbal formulations for diabetes complications. The aim of this study is to evaluate the antidiabetic effect of extracts and compounds from H. ponga. MATERIALS AND METHODS: Silica gel column chromatography was performed to identify various chemical components of the plant extract. Different extracts of H. ponga and isolated compounds were screened for their antidiabetic effect by modulation of digestive enzymes and protein glycation. The effect of glucose uptake by the compounds and the pathways through which the compounds mediate the glucose uptake potential were confirmed by fluorescent microscopy, flow cytometry and western blot analysis. RESULTS: Acetone and ethanol extracts of the stem bark of Hopea ponga (Dennst.) Mabb. Afforded six resveratrol oligomers namely, E-resveratrol (1), (-)-ε-viniferin (2), (-)-α-viniferin (3), trihydroxyphenanthrene glucoside (THPG) (4), vaticaphenol A (5), (-)-hopeaphenol (6), along with four phytosterols. The structures were determined on the basis of spectroscopic analyses including nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry (HRMS) data. Compounds 1-5 and 7-10 were tested for their α-glucosidase, α-amylase and glycation inhibitiory activities. All the resveratrol oligomers (1-5) showed prominent α-glucosidase inhibition with IC50 values, 12.56⯱â¯1.00, 23.98⯱â¯1.11, 7.17⯱â¯1.10, 31.74⯱â¯0.42 and 16.95⯱â¯0.39⯵M, respectively. Molecular docking studies also supported the observed α-glucosidase inhibition. Compound 3 displayed IC50 values of 4.85⯱â¯0.06 and 27.10⯱â¯0.04⯵M in α-amylase and glycation inhibitory assays activity. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay revealed that the compounds 3 and 4 were found to be less toxic at a concentration of 100⯵M (<10%) and 25⯵M (<20%), respectively. The effect of glucose uptake performed by 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) in L6 myoblast were measured by fluorescent microscopy and flow cytometry. The compounds 3 and 4 showed 2-NBDG uptake of 49.6% and 38.8% respectively. By examining the molecular pathway through which the compounds elicit their glucose uptake potential, it was observed that both the compounds mainly act via AMPK pathway. CONCLUSION: This is the first report on the isolation of compounds from H. ponga. Altogether, the results of this study reveal the antidiabetic effects of H. ponga extracts and isolated compounds promoting traditional use of this plant in the treatment of diabetes.
Asunto(s)
Dipterocarpaceae/química , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Resveratrol/farmacología , Acetona/química , Animales , Línea Celular , Diabetes Mellitus/tratamiento farmacológico , Pruebas de Enzimas , Etanol/química , Glicosilación/efectos de los fármacos , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Concentración 50 Inhibidora , Medicina Tradicional/métodos , Simulación del Acoplamiento Molecular , Estructura Molecular , Mioblastos , Corteza de la Planta/química , Extractos Vegetales/química , Tallos de la Planta/química , Ratas , Resveratrol/química , Resveratrol/aislamiento & purificación , Pruebas de Toxicidad , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/química , alfa-Amilasas/metabolismo , alfa-Glucosidasas/química , alfa-Glucosidasas/metabolismoRESUMEN
BACKGROUND: Resveratrol, an extensively recognized phytochemical that belongs to the stilbene family, is abundant in grape peel which is discarded as a by-product during grape juice processing. RESULTS: In this study, we established that pre-heating grape peel above 75 °C significantly improved the extractability of resveratrol and its glucoside piceid. In particular, thermal heating of grape peel at 95 °C for 10 min, followed by treatment with a mixture of exo-1,3-ß-glucanase and pectinases at 50 °C for 60 min, dramatically increased the conversion of piceid into resveratrol and the overall extractability of this phytochemical by 50%. Furthermore, thermal pre-treatment promoted a substantial increase in the total phenol, flavonoid, and anthocyanin concentrations in the grape peel extract. Ultimately, resveratrol-enriched grape peel extract significantly augmented the antioxidant response in vitro, possibly by attenuating the accumulation of intracellular reactive oxygen species via the Nrf2 signaling pathway. CONCLUSION: The method developed in this study for preparing grape peel extract introduces a potential low-cost green processing for the industrial fortification of food products with resveratrol and other health-beneficial antioxidants. © 2019 Society of Chemical Industry.
Asunto(s)
Antioxidantes/química , Manipulación de Alimentos/métodos , Extractos Vegetales/química , Resveratrol/química , Vitis/química , Antioxidantes/aislamiento & purificación , Biocatálisis , Manipulación de Alimentos/instrumentación , Frutas/química , Glucano 1,3-beta-Glucosidasa/química , Calor , Extractos Vegetales/aislamiento & purificación , Poligalacturonasa/química , Resveratrol/aislamiento & purificación , Residuos/análisisRESUMEN
The aim of present study was to evaluate the action of green tea and its constituents on rabbit ovarian functions and some non-reproductive indexes. In in vitro experiments, rabbit ovarian fragments were cultured with green tea constituents - epigallocatechin-3-gallate (EGCG), green tea polyphenols (GTPP) and resveratrol (RSV) (at 0, 1, 10 or 100⯵g/mL medium). The accumulation of an apoptosis marker - caspase 3 and the release of progesterone (P4) and testosterone (T) were measured. In in vivo experiments, does were fed a standard diet or a diet enriched with green tea powder. The weight gain, mortality, ovarian length and weight, conception and kindling rate, number of liveborn, stillborn, and weaned pups, diameter of ovarian follicles and some blood haematological and biochemical parameters were analysed. Culture of ovarian fragments with EGCG increased accumulation of caspase 3, whilst both GTTP and RSV decreased it. EGCG inhibited both P4 and T output, GTPP stimulated P4 and inhibited T, whilst RSV promoted release of both P4 and T. Feeding with green tea increased ovarian length and diameter of ovarian non-ovulated peri-ovulatory haemorrhagic but not of primary and secondary growing follicles. Furthermore, green tea reduced conception and kindling rate, the number of liveborn and weaned pups, increased female mortality but not their weight gain. It reduced platelet distribution width, but it did not affect other haematological and biochemical indexes. These observations suggest that dietary green tea can reduce rabbit doe's viability, ovarian functions and fecundity, perhaps due to changes in ovarian cell apoptosis, steroid hormones release and blockade of the ovulation of large ovarian follicles. The anti-reproductive action of green tea could be due to its constituent - EGCG with pro-apoptotic and anti-steroid hormone properties.