RESUMEN
PURPOSE: High glucose level is a strong initiator of both oxidative stress and DNA damage to various cellular proteins. This activates the poly ADP-ribose polymerase (PARP) enzyme, which is responsible for disturbing physiological energy metabolic homeostasis. The present study aimed to elucidate the association between stress and the PARP pathway by using resveratrol (RSV) and nicotinamide (NAM, PARP inhibitor) to treat diabetic cataract. METHOD: Albino rats were used for the experimental study. A single streptozotocin administration (55 mg/kg, i.p.) prompted diabetes in the animals. The experimental groups were the normal group (non-diabetic) and the diabetic groups: the diabetic control animals (group D), the diabetic animals treated with RSV at 40 mg/kg/day, i.p. (D+ RSV group), NAM at 100 and 300 mg/kg/day, i.p. (D+ NAM100, D+ NAM300 groups, respectively), and a combination of RSV and NAM i.p. (D+ RSV+NAM100 = Combi 1 group, D+ RSV+NAM300 = Combi 2 group). Glucose levels and the eyes were examined biweekly; various cataractogenic parameters in the lenses were examined after completion of the eight-week experimental protocol. RESULTS: Compared to diabetic control, RSV monotherapy significantly decreased hyperglycemia and other lenticular alterations. NAM at the high dose only showed beneficial effects without altering the blood glucose level, lenticular aldose reductase (AR) activity, and sorbitol content, primarily restored the lenticular NAD level and decreased oxidative stress in diabetic rats. These findings regarding NAM treatment indicate that a pathway other than the antioxidant defense system and the polyol pathway, which might be due to PARP inhibition, is involved in diabetic cataracts. Moreover, compared to RSV monotherapy, combination treatments were effective. CONCLUSION: These results indicate that hyperglycemia and oxidative-osmotic-nitrosative stress play central roles in the pathophysiology of diabetic cataracts. Moreover, our study also revealed that concurrent treatment with the RSV and NAM may prove useful in the pharmacotherapy of diabetes and its secondary complications such as cataract.
Asunto(s)
Catarata/prevención & control , Diabetes Mellitus Experimental/prevención & control , Niacinamida/uso terapéutico , Resveratrol/uso terapéutico , Aldehído Reductasa/metabolismo , Animales , Antioxidantes/uso terapéutico , Glucemia/metabolismo , Catarata/metabolismo , Catarata/patología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Quimioterapia Combinada , Hiperglucemia , Inyecciones Intraperitoneales , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Ratas , Ratas Sprague-Dawley , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Sorbitol/metabolismo , Estreptozocina , Complejo Vitamínico B/uso terapéuticoRESUMEN
The feedback regulation of photosynthesis depends on the cooperation of multiple signals, including sugars. Herein, the effect of shoot girdling was monitored on a daily basis for three days in green- and red-leafed Prunus cerasifera plants (GLP and RLP, respectively). The effect of anthocyanin presence was investigated in terms of photosynthesis, sugar metabolism and photoprotection. Net photosynthesis (A390) and stomatal conductance were reduced on the first day at 12:00 only in the girdled GLP (29 and 33 %, respectively). Moreover, the girdled GLP displayed at 12:00 higher sucrose, glucose and fructose concentrations than control leaves. Conversely, girdled RLP showed the first reduction of A390 at 18:00, with no significant differences at 12:00 in sucrose and glucose concentrations. The increased biosynthesis of anthocyanins that was only detected in girdled RLP contributed to lowering the accumulation of hexoses. Overall, these results revealed a sugar-buffering role exerted by anthocyanins that positively influence the feedback regulation of photosynthesis. Moreover, non-photochemical quenching, namely pNPQ, revealed the ability of anthocyanins to photoprotect photosystem II from supernumerary photons reaching the chloroplast, whose function was compromised by girdling. The present study provides a starting point to understand the possible link between photosynthesis regulation through sugar signalling and anthocyanin upregulation.
Asunto(s)
Antocianinas/metabolismo , Prunus domestica/metabolismo , Antocianinas/genética , Fotosíntesis/genética , Fotosíntesis/fisiología , Sorbitol/metabolismo , Almidón/metabolismoRESUMEN
KEY MESSAGE: Poplar callus maintained a specific difference in osmotic potential with respect to media when supplemented with different carbohydrate concentrations. This balance in osmotic potential guaranteed the growth capacity. Osmotic stress is caused by several abiotic factors such as drought, salinity, or freezing. However, the threshold of osmotic potential that allows the growth under stress conditions has not been thoroughly studied. In this study, different levels of osmotic stress in Populus alba (L.) callus have been induced with the addition of mannitol or sorbitol in the medium (from 0 to 500 mM). The key factor for preserving the growth was observed to be the restoration of a constant difference in osmotic potential between callus and medium for all the tested conditions. The osmotic adjustments were primarily achieved with the uptake of mannitol or sorbitol from the media considering their chemical properties instead of their biological functions. The decrease in water content (from - 1 to - 10% after 21 days) and mineral elements, such as potassium, calcium, and magnesium, together with the alterations in cell morphology, did not show negative effects on growth. The activity of sorbitol dehydrogenase was detected for the first time in poplar (+ 4.7 U l-1 in callus treated with sorbitol compared to control callus). This finding suggested the importance of choosing carefully the molecules used to exert osmotic stress for separating the dual function of carbohydrates in osmotic adjustments and cell metabolism.
Asunto(s)
Carbohidratos/farmacología , Presión Osmótica , Populus/citología , Proliferación Celular/efectos de los fármacos , Pared Celular/metabolismo , Pared Celular/ultraestructura , Células Cultivadas , Medios de Cultivo , Congelación , L-Iditol 2-Deshidrogenasa/metabolismo , Manitol/metabolismo , Minerales/metabolismo , Populus/ultraestructura , Análisis de Componente Principal , Análisis de Regresión , Solubilidad , Sorbitol/metabolismo , Almidón/metabolismo , Azúcares/metabolismo , Agua/metabolismoRESUMEN
6-(N-hydroxyethyl) amino-6-deoxy-l-sorbofuranose (6NSL) is the direct precursor of miglitol for diabetes therapy. The regio- and stereo-selective dehydrogenation offered by the membrane-bound d-sorbitol dehydrogenase (mSLDH) from Gluconobacter oxydans provides an elegant enzymatic method for 6NSL production. In this study, two subunits sldA and sldB of mSLDH were introduced into G. oxydans ZJB-605, and the specific enzyme activity of mSLDH towards NHEG was enhanced by 2.15-fold. However, the endogenous PQQ level was dramatically reduced in the recombinant strain and became a bottleneck to support the holo-enzyme activity. A combined supplementation of four amino acids (Glu, Ile, Ser, Arg) involved in biosynthesis of PQQ in conventional media effectively increased extracellular accumulation of PQQ by 1.49-fold, which further enhanced mSLDH activity by 1.33-fold. The synergic improvement of mSLDH activity provided in this study supports the superior high dehydrogenate activity towards substrate N-2-hydroxyethyl-glucamine, 184.28 g·L-1 of 6NSL was produced after a repeated bioconversion process catalyzed by the resting cells of G. oxydans/pBB-sldAB, all of which presenting a great potential of their industrial application in 6NSL biosynthesis.
Asunto(s)
Proteínas Bacterianas/metabolismo , Gluconobacter oxydans/metabolismo , L-Iditol 2-Deshidrogenasa/metabolismo , Cofactor PQQ/biosíntesis , Sorbosa/análogos & derivados , 1-Desoxinojirimicina/análogos & derivados , 1-Desoxinojirimicina/metabolismo , Aminoácidos/análisis , Proteínas Bacterianas/genética , Reactores Biológicos , Medios de Cultivo/química , Fermentación , Expresión Génica , Gluconobacter oxydans/enzimología , Gluconobacter oxydans/genética , Hipoglucemiantes/metabolismo , L-Iditol 2-Deshidrogenasa/genética , Cofactor PQQ/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Sorbitol/metabolismo , Sorbosa/biosíntesisRESUMEN
Resveratrol, which is a polyphenol found in grapes, peanuts, and other plants, has health benefits for various chronic diseases. The aim of the present study was to examine the effect of resveratrol on cataract formation in diabetic rats. Male Wistar rats (7-week-old) were treated with streptozotocin, and the streptozotocin-treated animals were administered 5% D-glucose in drinking water to promote the formation of cataracts by inducing severe hyperglycemia. Resveratrol supplementation (10 or 30 mg/kg/d) in drinking water was initiated immediately after induction of diabetes was confirmed. The full lens images of the horizontal plane were captured with the digital camera system which we developed. Cataract formation was assessed by an observer-based scoring method and by quantitative analysis of digital images of the lens. Cataracts at the peripheral region of the lens were detected 2 weeks after induction of hyperglycemia and progressed depending on the length of the diabetic period. The majority of them developed severe cataracts after 9 weeks of hyperglycemia. Resveratrol did not prevent the appearance of diabetic cataracts but significantly delayed the progression of cataracts compared with controls. The contents of sorbitol and protein carbonyls in lenses of diabetic rats were higher than those of control rats. Resveratrol suppressed the increase in protein carbonyls, but not of sorbitol, in diabetic lenses. These results suggest that resveratrol delays the progression of diabetic cataracts partially through attenuation of oxidative damage to lens proteins. Resveratrol may be beneficial in preventing the progression of diabetic cataracts.
Asunto(s)
Glucemia/metabolismo , Catarata/prevención & control , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Experimental/tratamiento farmacológico , Cristalino/efectos de los fármacos , Fitoterapia , Resveratrol/uso terapéutico , Aldehído Reductasa , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Catarata/etiología , Cristalinas/metabolismo , Complicaciones de la Diabetes/etiología , Diabetes Mellitus Experimental/complicaciones , Suplementos Dietéticos , Glucosa , Hiperglucemia/complicaciones , Hiperglucemia/etiología , Cristalino/metabolismo , Cristalino/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Carbonilación Proteica , Ratas Wistar , Resveratrol/farmacología , Sorbitol/metabolismoRESUMEN
In the previous study, the artichoke leaf extract showed effective inhibition of AKR1B1, the first enzyme of polyol pathway, which reduces high level of glucose to osmotically active sorbitol, important for development of chronic diabetic complications. In the present study, the effect of artichoke leaf extract and of several participating phenols (caffeic acid, chlorogenic acid, quinic acid, and luteolin) was tested on sorbitol level in rat lenses exposed to high glucose ex vivo, on cytotoxicity as well as on oxidative stress in C2C12 muscle cell line induced by high glucose in vitro. The concentration of sorbitol was determined by enzymatic analysis, the cytotoxicity was provided by WST-1 test and intracellular content of reactive oxygen species was determined by fluorescence of 2'-7'-dichlorofluorescein probe. The extract and the compounds tested showed significant protection against toxic effects of high concentration of glucose in both models. On balance, the artichoke leaf extract thus represents a prospective preventive agent of development of chronic diabetic complications, probably due to phenols content, concerning preclinical and clinical studies.
Asunto(s)
Cynara scolymus/química , Glucosa/farmacología , Cristalino/efectos de los fármacos , Extractos Vegetales/farmacología , Hojas de la Planta/química , Sorbitol/metabolismo , Aldehído Reductasa/antagonistas & inhibidores , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Cristalino/metabolismo , Ratones , Técnicas de Cultivo de Órganos , Estrés Oxidativo/efectos de los fármacos , Ratas , Especies Reactivas de Oxígeno/farmacologíaRESUMEN
We investigated sugar metabolism in leaves and fruits of two Japanese plum (Prunus salicina Lindl.) cultivars, the climacteric Santa Rosa and its bud sport mutant the non-climacteric Sweet Miriam, during development on the tree. We previously characterized differences between the two cultivars. Here, we identified key sugar metabolic pathways. Pearson coefficient correlations of metabolomics and transcriptomic data and weighted gene co-expression network analysis (WGCNA) of RNA sequencing (RNA-Seq) data allowed the identification of 11 key sugar metabolism-associated genes: sucrose synthase, sucrose phosphate synthase, cytosolic invertase, vacuolar invertase, invertase inhibitor, α-galactosidase, ß-galactosidase, galactokinase, trehalase, galactinol synthase, and raffinose synthase. These pathways were further assessed and validated through the biochemical characterization of the gene products and with metabolite analysis. Our results demonstrated the reprogramming of sugar metabolism in both leaves and fruits in the non-climacteric plum, which displayed a shift towards increased sorbitol synthesis. Climacteric and non-climacteric fruits showed differences in their UDP-galactose metabolism towards the production of galactose and raffinose, respectively. The higher content of galactinol, myo-inositol, raffinose, and trehalose in the non-climacteric fruits could improve the ability of the fruits to cope with the oxidative processes associated with fruit ripening. Overall, our results support a relationship between sugar metabolism, ethylene, and ripening behavior.
Asunto(s)
Frutas/metabolismo , Hojas de la Planta/metabolismo , Prunus domestica/genética , Sorbitol/metabolismo , Transcriptoma , Frutas/crecimiento & desarrollo , Hojas de la Planta/crecimiento & desarrollo , Prunus domestica/crecimiento & desarrollo , Prunus domestica/metabolismo , Azúcares/metabolismoRESUMEN
In this study, the effect of rate-limiting enzymes involved in degradation of hepatic adenosine and intracellular sorbitol was investigated in rats exposed to haloperidol (HAL) and treated with functional oil (FO), containing principal active phytochemicals from black seed. Animals were divided into six groups (n=10): Distilled water, HAL 15 mg/kg, pre-administration/HAL 15 mg/kg, co-administration/HAL 15 mg/kg, post-administration/HAL 15 mg/kg, FO 150 mg/kg. The results of this study revealed that the activities of ectonucleotidase and aldose-reductase were significantly increased in HAL-treated rats when compared with the control (p < 0.05). However, differential treatments (pre, co and post) with FO depleted the activities of these enzymes compared with HAL-treated rats. Furthermore, therapeutic HAL administration increased the levels of key hepatic biomarkers (ALT, AST, and ALP) and malondialdehyde level with a concomitant decrease in functional hepatic cellular ATP. However, differential treatment with FO increases hepatic ATP and non-enzymatic antioxidant status, with a concomitant decrease in the levels of malondialdehyde and liver biomarkers. Therefore, results of this finding underlined the importance of aldose-reductase and econucleotidase activities in HAL induced toxicity and suggest some possible mechanisms of action by which FO prevent HAL-induced hepatic toxicity in rats.
Asunto(s)
5'-Nucleotidasa/metabolismo , Aldehído Reductasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Metabolismo Energético/efectos de los fármacos , Haloperidol/efectos adversos , Hígado/enzimología , Hígado/metabolismo , Fitoquímicos/farmacología , Aceites de Plantas/farmacología , Regulación hacia Arriba/efectos de los fármacos , Adenosina/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Proteínas Ligadas a GPI/metabolismo , Masculino , Malondialdehído/metabolismo , Fitoquímicos/administración & dosificación , Fitoquímicos/química , Aceites de Plantas/administración & dosificación , Aceites de Plantas/química , Ratas Wistar , Semillas/química , Sorbitol/metabolismoRESUMEN
Ophicordyceps sinensis is a well-known traditional Chinese medicine and cultured mycelium is a substitute for wild O. sinensis. Metabolic profiles of wild O. sinensis from three geographical locations and cultivated mycelia derived from three origins were investigated using (1)H nuclear magnetic resonance (NMR) analysis combined with multivariate statistical analysis. A total of 56 primary metabolites were identified and quantified from O. sinensis samples. The principle component analysis (PCA) showed significant differences between natural O. sinensis and fermentation mycelia. Seven metabolites responsible for differentiation were screened out by orthogonal partial least squares discriminant analysis (OPLS-DA). The concentrations of mannitol, trehalose, arginine, trans-4-hydroxyproline, alanine and glucitol were significantly different between wild and cultured groups. The variation in metabolic profiling among artificial mycelia was greater than that among wild O. sinensis. Furthermore, wild samples from different origins were clearly distinguished by the levels of mannitol, trehalose and some amino acids. This study indicates that (1)H NMR-based metabolomics is useful for fingerprinting and discriminating O. sinensis of different geographical regions and cultivated mycelia of different strains. The present study provided an efficient approach for investigating chemical compositions and evaluating the quality of medicine and health food derived from O. sinensis.
Asunto(s)
Cordyceps/metabolismo , Metabolómica/métodos , Espectroscopía de Protones por Resonancia Magnética , Alanina/metabolismo , Cordyceps/crecimiento & desarrollo , Análisis Discriminante , Fermentación , Hidroxiprolina/metabolismo , Análisis de los Mínimos Cuadrados , Manitol/metabolismo , Análisis Multivariante , Análisis de Componente Principal , Sorbitol/metabolismo , Trehalosa/metabolismoRESUMEN
Parenteral nutrition (PN) is a life-saving nutritional support for a large population of hospitalized infants, and lipids make a substantial contribution to their energy and essential fatty acid (FA) needs. A challenge in the care of these infants is that their metabolic needs require prolonged PN support that increases the risk of PN-associated liver disease (PNALD). In recent years, the emergence of new parenteral lipid emulsions containing different source lipids and FA profiles has created nutritional alternatives to the first-generation, soybean oil-based lipid emulsion Intralipid. The limited U.S. introduction of the new-generation fish-oil emulsion Omegaven has generated promising results in infants with PNALD and spawned a renewed interest in how PN and lipid emulsions, in particular, contribute to this disease. Studies suggest that the lipid load and constituents, such as specific FAs, ratio of n-3 (ω-3) to n-6 (ω-6) long-chain polyunsaturated FAs, phytosterols, and vitamin E content, may be involved. There is an existing literature describing the molecular mechanisms whereby these specific nutrients affect hepatic metabolism and function via lipid and bile acid sensing nuclear receptors, such as peroxisome proliferator-activated receptor α, liver X receptor, and farnesoid X receptor, yet virtually no information as to how they interact and modulate liver function in the context of PN in pediatric patients or animal models. This article will review the recent development of parenteral lipid emulsions and their influence on PNALD and highlight some of the emerging molecular mechanisms that may explain the effects on liver function and disease.
Asunto(s)
Colestasis Intrahepática/prevención & control , Emulsiones Grasas Intravenosas/uso terapéutico , Ácidos Grasos Omega-3/uso terapéutico , Enfermedades del Prematuro/prevención & control , Estrés Oxidativo , Nutrición Parenteral Total/efectos adversos , Colestasis Intrahepática/etiología , Colestasis Intrahepática/metabolismo , Colestasis Intrahepática/terapia , Congresos como Asunto , Combinación de Medicamentos , Emulsiones Grasas Intravenosas/efectos adversos , Emulsiones Grasas Intravenosas/metabolismo , Ácidos Grasos Omega-3/efectos adversos , Ácidos Grasos Omega-3/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Aceites de Pescado/efectos adversos , Aceites de Pescado/metabolismo , Aceites de Pescado/uso terapéutico , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/etiología , Enfermedades del Prematuro/metabolismo , Enfermedades del Prematuro/terapia , Hígado/inmunología , Hígado/metabolismo , Fosfolípidos/efectos adversos , Fosfolípidos/metabolismo , Fosfolípidos/uso terapéutico , Aceites de Plantas/efectos adversos , Aceites de Plantas/metabolismo , Aceites de Plantas/uso terapéutico , Receptores Citoplasmáticos y Nucleares/metabolismo , Transducción de Señal , Sorbitol/efectos adversos , Sorbitol/metabolismo , Sorbitol/uso terapéutico , Aceite de Soja/efectos adversos , Aceite de Soja/metabolismo , Aceite de Soja/uso terapéutico , Receptor Toll-Like 4/metabolismo , Triglicéridos , Vitamina E/metabolismoRESUMEN
Curcumin, the active principle present in the yellow spice turmeric, has been shown to exhibit various pharmacological actions such as antioxidant, anti-inflammatory, antimicrobial, and anti-carcinogenic activities. Previously we have reported that dietary curcumin delays diabetes-induced cataract in rats. However, low peroral bioavailability is a major limiting factor for the success of clinical utilization of curcumin. In this study, we have administered curcumin encapsulated nanoparticles in streptozotocin (STZ) induced diabetic cataract model. Oral administration of 2 mg/day nanocurcumin was significantly more effective than curcumin in delaying diabetic cataracts in rats. The significant delay in progression of diabetic cataract by nanocurcumin is attributed to its ability to intervene the biochemical pathways of disease progression such as protein insolubilization, polyol pathway, protein glycation, crystallin distribution and oxidative stress. The enhanced performance of nanocurcumin can be attributed probably to its improved oral bioavailability. Together, the results of the present study demonstrate the potential of nanocurcumin in managing diabetic cataract.
Asunto(s)
Materiales Biocompatibles/química , Catarata/tratamiento farmacológico , Catarata/prevención & control , Curcumina/uso terapéutico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Nanopartículas/uso terapéutico , Aldehído Reductasa/metabolismo , Animales , Antioxidantes/metabolismo , Biodegradación Ambiental , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Catarata/sangre , Catarata/complicaciones , Cristalinas/química , Cristalinas/metabolismo , Curcumina/farmacología , Diabetes Mellitus Experimental/sangre , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Conducta Alimentaria/efectos de los fármacos , Insulina/sangre , Ácido Láctico/química , Cristalino/efectos de los fármacos , Cristalino/enzimología , Cristalino/patología , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Carbonilación Proteica/efectos de los fármacos , Ratas , Sorbitol/metabolismo , Estreptozocina , Superóxido Dismutasa/metabolismo , Resultado del TratamientoRESUMEN
Cryopreservation of plant species is poorly investigated in Brazil. The aim of this study was to cryopreserve Byrsonima intermedia shoot apical meristems through droplet vitrification. A culture medium for shoot-tips growth was established using the Woody Plant Medium supplemented with 2.22 uM 6-benzylaminopurine. Excised shoot-tips were subjected to pre-culture and/or post-culture treatments on Murashige and Skoog medium with 0.3 M sucrose for 24 h prior dehydration on PVS2 at 0°C for 15, 30 or 45 minutes prior to plunging in liquid nitrogen. The effect of 15 days of shoot pre-growth on a high osmotic medium (0.3 M sucrose or 0.21 M sorbitol + 0.09 M sucrose) prior to meristem excision and cryopreservation was also investigated. Pre-culturing shoot-tips on 0.3 M sucrose for 24 h prior to cryopreservation increased the regrowth level after thawing to 90%. Shoot-tips excised from shoots pre-grown on MS + 0.21 M sorbitol + 0.09 M sucrose for 15 days presented a satisfactory regrowth level (67%).
Asunto(s)
Criopreservación/métodos , Malpighiaceae/crecimiento & desarrollo , Brotes de la Planta/crecimiento & desarrollo , Vitrificación , Compuestos de Bencilo , Crioprotectores/metabolismo , Cinetina/metabolismo , Malpighiaceae/efectos de los fármacos , Meristema/efectos de los fármacos , Meristema/crecimiento & desarrollo , Brotes de la Planta/efectos de los fármacos , Plantas Medicinales/efectos de los fármacos , Plantas Medicinales/crecimiento & desarrollo , Purinas , Sorbitol/metabolismo , Sacarosa/metabolismoRESUMEN
Diabetic ophthalmopathy (DO) impairs patients' eyesight and even causes blindness. Here, we investigated the effect of 60% ethanol extract of the rhizome of Anemarrhenae asphodeloides (ERA), which is commonly used in Chinese medicine formulae in treating diabetes, on DO progression. Blood glucose, insulin, advanced glycation end products (AGE), super oxygen dehydrogenises (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) levels in serum and sorbitol concentration in the lens were measured. Retinal endothelium/pericyte (E/P) ratio was evaluated, and structural changes of the retina and lens were observed. Effects of mangiferin and neomangiferin, the two major components of ERA, on subnormal growth of pericytes induced by high glucose were also detected. It was found that the activities of SOD and GSH-Px in serum were increased, whereas MDA and AGE levels in serum and sorbitol concentration in the lens were decreased in ERA-treated DO rats. E/P ratio was decreased, and the pathological changes of the lens and retina were alleviated by ERA treatment. Moreover, the subnormal growth of pericytes induced by high glucose was ameliorated by mangiferin and neomangiferin. These results indicated that ERA could effectively prevent DO progression in streptozotocin-induced diabetic rats, and mangiferin and neomangiferin may be the main effective components.
Asunto(s)
Anemarrhena/química , Catarata/tratamiento farmacológico , Retinopatía Diabética/tratamiento farmacológico , Extractos Vegetales/farmacología , Rizoma/química , Animales , Glucemia/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucósidos/farmacología , Glutatión Peroxidasa/sangre , Productos Finales de Glicación Avanzada/sangre , Insulina/sangre , Cristalino/efectos de los fármacos , Cristalino/patología , Masculino , Malondialdehído/sangre , Pericitos/efectos de los fármacos , Ratas , Ratas Wistar , Retina/efectos de los fármacos , Retina/patología , Sorbitol/metabolismo , Estreptozocina , Superóxido Dismutasa/sangre , Xantonas/farmacologíaRESUMEN
As a continuation of our efforts directed towards the development of anti-diabetic agents from natural sources, piplartine was isolated from Piper chaba, and was found to inhibit recombinant human ALR2 with an IC(50) of 160 µM. To improve the efficacy, a series of analogues have been synthesized by modification of the styryl/aromatic and heterocyclic ring functionalities of this natural product lead. All the derivatives were tested for their ALR2 inhibitory activity, and results indicated that adducts 3c, 3e and 2j prepared by the Michael addition of piplartine with indole derivatives displayed potent ARI activity, while the other compounds displayed varying degrees of inhibition. The active compounds were also capable of preventing sorbitol accumulation in human red blood cells.
Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Inhibidores Enzimáticos/síntesis química , Hipoglucemiantes/síntesis química , Piper/química , Piperidonas/química , Aldehído Reductasa/química , Transporte Biológico/efectos de los fármacos , Diseño de Fármacos , Pruebas de Enzimas , Inhibidores Enzimáticos/farmacología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Humanos , Hipoglucemiantes/farmacología , Indoles/química , Simulación del Acoplamiento Molecular , Piperidonas/aislamiento & purificación , Extractos Vegetales/química , Raíces de Plantas/química , Proteínas Recombinantes/antagonistas & inhibidores , Proteínas Recombinantes/química , Sorbitol/antagonistas & inhibidores , Sorbitol/metabolismo , Relación Estructura-ActividadRESUMEN
Gas chromatography (GC)-based metabolomics technologies were applied for quality control of Angelicae Radix, an herbal medicine commonly used in Japan and China. Since Angelica roots are priced and graded differently based on their species and cultivation area, there is a need for a simple and reproducible method to discriminate Angelica roots. Here, we used GC-MS profiling data to construct a discrimination method for species and cultivation area of A. Radix. Seventy-six primary metabolites were identified. The quality factors of A. Radix were successfully classified using metabolic profiling and the orthogonal projections to latent structures-discriminant analysis (OPLS-DA) technique. Sorbitol and a glucose/4-aminobutyric acid combination were chosen as bio-markers from S-plot of OPLS-DA. Application of these selected bio-markers to a more practical and cost-efficient system, namely gas chromatography-flame ionization detector (GC-FID) system were also assessed. As a result, the same separations of sorbitol, glucose and 4-aminobutyric acid in box plots were obtained from GC-FID data. Our results demonstrate that GC-based metabolic markers can be readily applied for the establishment of a practical quality control method for A. Radix.
Asunto(s)
Angelica/metabolismo , Ionización de Llama/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Metaboloma , Metabolómica/instrumentación , Metabolómica/métodos , Plantas Medicinales/química , Angelica/química , Biomarcadores/análisis , Biomarcadores/química , Biomarcadores/metabolismo , Análisis Discriminante , Medicamentos Herbarios Chinos , Glucosa/análisis , Glucosa/química , Glucosa/metabolismo , Japón , Raíces de Plantas/química , Control de Calidad , Sorbitol/análisis , Sorbitol/química , Sorbitol/metabolismo , Ácido gamma-Aminobutírico/análisis , Ácido gamma-Aminobutírico/química , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Diabetes mellitus is recognized as a leading cause of new cases of blindness. The prevalence of diabetic eye disease is expected to continue to increase worldwide as a result of the dramatic increase in the number of people with diabetes. At present, there is no medical treatment to delay or prevent the onset and progression of cataract or retinopathy, the most common causes of vision loss in diabetics. The plant Emblica officinalis (gooseberry) has been used for thousands of years as a traditional Indian Ayurvedic preparation for the treatment of diabetes in humans. Extracts from this plant have been shown to be efficacious against the progression of cataract in a diabetic rat model. Aldose reductase (ALR2) is implicated in the development of secondary complications of diabetes including cataract and, therefore, has been a major drug target for the development of therapies to treat diabetic disease. Herein, we present the bioassay-guided isolation and structure elucidation of 1-O-galloyl-ß-D-glucose (ß-glucogallin), a major component from the fruit of the gooseberry that displays selective as well as relatively potent inhibition (IC(50) = 17 µM) of AKR1B1 in vitro. Molecular modeling demonstrates that this inhibitor is able to favorably bind in the active site. Further, we show that ß-glucogallin effectively inhibits sorbitol accumulation by 73% at 30 µM under hyperglycemic conditions in an ex-vivo organ culture model of lenses excised from transgenic mice overexpressing human ALR2 in the lens. This study supports the continued development of natural products such as ß-glucogallin as therapeutic leads in the development of novel therapies to treat diabetic complications such as cataract.
Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Frutas/química , Taninos Hidrolizables/aislamiento & purificación , Phyllanthus emblica/química , Extractos Vegetales/aislamiento & purificación , Aldehído Reductasa/química , Animales , Dominio Catalítico , Simulación por Computador , Humanos , Ácido Bromhídrico , Taninos Hidrolizables/química , Taninos Hidrolizables/farmacología , Cristalino/efectos de los fármacos , Cristalino/enzimología , Cristalino/metabolismo , Ratones , Modelos Moleculares , Oxidación-Reducción , Extractos Vegetales/química , Extractos Vegetales/farmacología , Unión Proteica , Sorbitol/metabolismo , Técnicas de Cultivo de TejidosRESUMEN
This critical review provides a survey illustrated by recent references of different strategies to achieve a sustainable conversion of biomass to bioproducts. Because of the huge number of chemical products that can be potentially manufactured, a selection of starting materials and targeted chemicals has been done. Also, thermochemical conversion processes such as biomass pyrolysis or gasification as well as the synthesis of biofuels were not considered. The synthesis of chemicals by conversion of platform molecules obtained by depolymerisation and fermentation of biopolymers is presently the most widely envisioned approach. Successful catalytic conversion of these building blocks into intermediates, specialties and fine chemicals will be examined. However, the platform molecule value chain is in competition with well-optimised, cost-effective synthesis routes from fossil resources to produce chemicals that have already a market. The literature covering alternative value chains whereby biopolymers are converted in one or few steps to functional materials will be analysed. This approach which does not require the use of isolated, pure chemicals is well adapted to produce high tonnage products, such as paper additives, paints, resins, foams, surfactants, lubricants, and plasticisers. Another objective of the review was to examine critically the green character of conversion processes because using renewables as raw materials does not exempt from abiding by green chemistry principles (368 references).
Asunto(s)
Biomasa , Biopolímeros/biosíntesis , Biopolímeros/química , Furaldehído/análogos & derivados , Furaldehído/síntesis química , Furaldehído/química , Tecnología Química Verde , Ácido Láctico/biosíntesis , Ácido Láctico/química , Ácidos Levulínicos/química , Lignina/química , Aceites de Plantas/química , Polisacáridos/química , Sorbitol/metabolismo , Ácido Succínico/síntesis química , Ácido Succínico/química , Triglicéridos/químicaRESUMEN
A flavanol glycoside, glucodistylin (1) and three polyphenol derivatives, gallate (2), (+)-catechin (3) and (+)-gallocatechin (4) were isolated from an aqueous acetone extract of the bark of Quercus acutissima. Of these compounds, glucodistylin exhibited uncompetitive inhibitory activity against recombinant human aldose reductase with an IC(50) value of 7.2 µM. Furthermore, glucodistylin inhibited sorbitol accumulation by 48.84% at 50 µM. This flavonoid showed therapeutic potential in the prevention and treatment of diabetes-related complications.
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Aldehído Reductasa/antagonistas & inhibidores , Catequina/análogos & derivados , Catequina/farmacología , Flavonoides/farmacología , Flavonoles/farmacología , Glicósidos/farmacología , Fenoles/farmacología , Quercus , Sorbitol/metabolismo , Aldehído Reductasa/metabolismo , Catequina/química , Catequina/aislamiento & purificación , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/prevención & control , Evaluación Preclínica de Medicamentos , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoles/química , Flavonoles/aislamiento & purificación , Glicósidos/química , Glicósidos/aislamiento & purificación , Humanos , Terapia Molecular Dirigida , Fenoles/química , Fenoles/aislamiento & purificación , Corteza de la Planta , Polifenoles , Proteínas Recombinantes/antagonistas & inhibidoresRESUMEN
BACKGROUND: This study analysed the content of ascorbic acid, phenolic acids and flavonoids in aqueous and ethanol extracts of pepino (Solanum muricatum Ait.), and examined the protective effects of pepino aqueous extract (PAE) in a mouse model of diabetes. PAE at 1, 2 and 4% was supplied for 5 weeks. RESULTS: Aqueous and ethanol extracts had similar levels of total phenolic acids, but PAE had a higher content of ascorbic acid and total flavonoids than the ethanol extract. PAE treatments at 2% and 4% significantly lowered plasma glucose level (P < 0.05); however, only the 4% PAE significantly elevated plasma insulin level at week 5 (P < 0.05). PAE treatments significantly decreased the levels of malonyldialdehyde and reactive oxygen species in kidney (P < 0.05); however, only the 2% and 4% treatments significantly reduced oxidised glutathione formation, increased glutathione level, and retained renal glutathione peroxidase and catalase activities (P < 0.05). PAE treatments at 2% and 4% significantly lowered renal interleukin (IL)-6 and tumour necrosis factor-α levels (P < 0.05); however, only the 4% treatments significantly diminished renal IL-1ß and levels of monocyte chemoattractant protein-1 (P < 0.05). PAE treatments at 4% significantly decreased aldose reductase activity and sorbitol production in kidney (P < 0.05). CONCLUSION: These findings support the suggestion that pepino aqueous extract could attenuate the progression of diabetes via its antioxidative, anti-inflammatory and antiglycative effects.
Asunto(s)
Antioxidantes/uso terapéutico , Ácido Ascórbico/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Fitoterapia , Polifenoles/uso terapéutico , Solanum/química , Aldehído Reductasa/metabolismo , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Glucemia/metabolismo , Catalasa/metabolismo , Quimiocina CCL2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Frutas , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Hipoglucemiantes/farmacología , Insulina/sangre , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Polifenoles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sorbitol/metabolismoRESUMEN
Eight yellow-pigmented, Gram-negative, rod-shaped, oxidase-negative, motile, facultatively anaerobic bacteria were isolated from onion seed in South Africa and from an onion plant exhibiting centre rot symptoms in the USA. The isolates were assigned to the genus Pantoea on the basis of phenotypic and biochemical tests. 16S rRNA gene sequence analysis and multilocus sequence analysis (MLSA), based on gyrB, rpoB, infB and atpD sequences, confirmed the allocation of the isolates to the genus Pantoea. MLSA further indicated that the isolates represented a novel species, which was phylogenetically most closely related to Pantoea ananatis and Pantoea stewartii. Amplified fragment length polymorphism analysis also placed the isolates into a cluster separate from P. ananatis and P. stewartii. Compared with type strains of species of the genus Pantoea that showed >97â% 16S rRNA gene sequence similarity with strain BD 390(T), the isolates exhibited 11-55â% whole-genome DNA-DNA relatedness, which confirmed the classification of the isolates in a novel species. The most useful phenotypic characteristics for the differentiation of the isolates from their closest phylogenetic neighbours are production of acid from amygdalin and utilization of adonitol and sorbitol. A novel species, Pantoea allii sp. nov., is proposed, with type strain BD 390(T) (â=âLMG 24248(T)).