RESUMEN

We have studied the effects of individual and combined treatment of insulin (I) and naringin (NAR) on the bone structure and biomechanical properties of femurs from streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were divided into five groups: (1) controls, (2) STZ-induced diabetic rats, (3) STZ-induced diabetic rats treated with I, (4) STZ-induced diabetic rats treated with NAR, and (5) STZ-induced diabetic rats treated with I + NAR. Bone mineral density (BMD), bone histomorphometry, biomechanical testing, and bone biomarker expressions were accomplished in femur of all animals, as well as serum biochemical analyses. The combined treatment of I + NAR increased the body weight and the femur BMD from STZ-induced diabetic rats. The bone biomechanical properties and the bone morphology of the femurs from STZ-induced diabetic rats were also improved by the combined treatment. The increased number of osteoclasts in STZ-induced diabetic rats was partially prevented by I, NAR, or I + NAR. NAR or I + NAR completely blocked the decrease in the number of osteocalcin (+) cells in the femur from STZ-induced diabetic rats. RUNX family transcription factor 2 immunostaining was much lower in STZ-induced diabetic rats than in control animals; the combination of I + NAR totally blocked this effect. The combined treatment not only ameliorated bone quality and function, but also normalized the variables related to glucose metabolism. Therefore, the combination of I + NAR might be a better therapeutic strategy than the individual I or NAR administration to reduce bone complications in diabetic patients.

Asunto(s)

Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Flavanonas , Humanos , Ratas , Masculino , Animales , Diabetes Mellitus Tipo 1/complicaciones , Insulina , Ratas Wistar , Diabetes Mellitus Experimental/complicaciones , Densidad Ósea

RESUMEN

Naringin (NRG) is a flavonoid with recognized cardioprotective effects. Then, it was investigated the cardioprotective mechanisms of NRG against ischemia-reperfusion (I/R) injury. The rats were pretreated for 7 days (v.o.) with NRG (25 mg/kg) or n-acetylcysteine (NAC, 100 mg/kg) and their isolated hearts were subjected to global ischemia (30 min) and reperfusion (60 min). Furthermore, isolated hearts were perfused with 5 µM NRG in the presence of 10 µM glibenclamide (GLI) and subjected to I/R protocol. In healthy ventricular cardiomyocyte, it was evaluated the acute effect of 5 µM NRG on the GLI sensitive current. The results showed that NRG pretreatment restored the cardiac function and electrocardiogram (ECG) alterations induced by I/R injury, decreasing arrhythmia scores and the occurrence of severe arrhythmias. Lactate dehydrogenase and infarct area were decreased while superoxide dismutase (SOD), catalase and citrate synthase activities increased. Expression of SOD CuZn and SOD Mn not was altered. NRG treatment decreased reactive oxygen species (ROS) generation and lipid peroxidation without alter sulfhydryl groups and protein carbonylation. Also, NRG (5 µM) increased the glibenclamide sensitive current in isolated cardiomyocytes. In isolated heart, the cardioprotection of NRG was significantly reduced by GLI. Furthermore, NRG promoted downregulation of Bax expression and Bax/Bcl-2. Histopathological analysis showed that NRG decreased cell edema, cardiomyocytes and nucleus diameter. Thus, NRG has a cardioprotective effect against cardiac I/R injury which is mediated by its antioxidant and antiapoptotic actions and KATP channels activation.

RESUMEN

Polyphenols comprise a number of natural substances, such as flavonoids, that show interesting biological effects. Among these substances is naringin, a naturally occurring flavanone glycoside found in citrus fruits and Chinese medicinal herbs. Several studies have shown that naringin has numerous biological properties, including cardioprotective, cholesterol-lowering, anti-Alzheimer's, nephroprotective, antiageing, antihyperglycemic, antiosteoporotic and gastroprotective, anti-inflammatory, antioxidant, antiapoptotic, anticancer and antiulcer effects. Despite its multiple benefits, the clinical application of naringin is severely restricted due to its susceptibility to oxidation, poor water solubility, and dissolution rate. In addition, naringin shows instability at acidic pH, is enzymatically metabolized by ß-glycosidase in the stomach and is degraded in the bloodstream when administered intravenously. These limitations, however, have been overcome thanks to the development of naringin nanoformulations. This review summarizes recent research carried out on strategies designed to improve naringin's bioactivity for potential therapeutic applications.

RESUMEN

We have studied the effects of naringin (NAR), a flavonoid from citric fruits, on morphology, ultrastructure and function of the kidney in streptozotocin (STZ)-induced diabetic rats. Two groups of animals were used: (1) control rats and (2) STZ rats (60 mg STZ/kg b.w.). At 3 days after induction, one group of STZ-treated rats received 40 mg NAR/kg b.w. daily. NAR blocked completely alterations in the biochemical renal markers in STZ rats except the increase in serum urea that was partially avoided by the flavonoid. NAR ameliorated the kidney morphological lesions from STZ rats. STZ treatment induced round and smaller mitochondria, which was avoided by NAR. Citrate synthase, isocitrate and malate dehydrogenases, enzyme activities of the Krebs cycle, were decreased in STZ rats. NAR abolished this decrease in the latter proteins. NAR also prevented a decrease in the ATP synthase activity of the mitochondria from renal cortex by about 49% in STZ rats, returning the enzyme activity to control values. The nephroprotection caused by NAR is mediated through counteraction of oxidative stress in mitochondria of proximal tubules. NAR might be a therapeutic strategy to reduce the complication of diabetic nephropathy in type 1 diabetic patients.

Asunto(s)

Diabetes Mellitus Experimental , Nefropatías Diabéticas , Flavanonas , Ratas , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Estrés Oxidativo , Flavanonas/farmacología , Flavanonas/uso terapéutico , Flavanonas/metabolismo , Riñón , Estreptozocina/farmacología , Mitocondrias/metabolismo

RESUMEN

Citrus paradisi species belong to the Rutaceae family, and it is commonly known as grapefruit. Grapefruit consumption involves a large amount of waste that goes to landfills and produces significant pollution affecting the human health. To examine this phenomenon, we designed an efficient chemical method that recovers naringin-rich flavonoid extracts from the fresh waste of grapefruits, by using the solvent impregnation resin method (SIR) with XAD-4 amberlite and either methanol or water as elution systems. Additionally, we focused on evaluating these extracts' anxiolytic- and antidepressant-like effects in behavioral predictive paradigms in mice. According to direct Principal Component Analysis (PCA) by NMR, and Direct Injection Electrospray Ionization-Mass Spectrometry (DIESI-MS), methanol extracts obtained after resin treatment were free of coumarin compounds and evinced had a high content of naringin. Poncirin, phenylalanine, chrysin 5,7-dimethyl ether, 5,7-dimethoxy-4'-hydroxyflavanone, 2,3-dihydro-2-(4-hydroxyphenyl)-5,6,7,8-tetramethoxy-4H-1-benzopyran-4-one, tetrahydrocurcumin, corchoionoside C, 6'-coumaroyl-1'-O-[2-(3,4-dihydroxyphenyl) ethyl]-ß-D-glucopyranoside were also detected. Naringin-rich methanol extract caused a clear anxiolytic-like effect in the Elevated Plus Maze (EPM) and the Hole-Board (HBT) Tests, increasing oral doses of this extract did not produce a sedative effect. A single oral dose caused an antidepressant-like effect in the Tail Suspension Test (TST), while repeated administrations of the methanol extract elicited a robust antidepressant effect in the Forced Swimming Test (FST) in mice. Our evidence highlights the importance of bioprospecting studies of organic waste with therapeutic potentials, such as anxiety and depression disorders.

Asunto(s)

Ansiolíticos , Humanos , Animales , Ratones , Ansiolíticos/química , Metanol/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antidepresivos/farmacología , Ansiedad/tratamiento farmacológico , Depresión/tratamiento farmacológico

RESUMEN

Naringin and limonin are the two main bitter compounds of citrus products such as grapefruit juice. The aim of this investigation was to evaluate the reduction in both bitter components simultaneously using a combined biochemical and physical approach. The proposed strategy was based on the use of heterofunctional supports with glyoxyl groups that allow for the covalent immobilization of naringinase, which hydrolyses naringin and alkyl groups that allow for the adsorption of limonin. The supports were butyl-glyoxyl agarose (BGA) and octyl-glyoxyl agarose (OGA), which were characterized in terms of aldehyde group quantification and FTIR analysis. The optimal pH and temperature of free and immobilized enzymes were assessed. The maximum enzyme loading capacity of supports was analyzed. Debittering of grapefruit juice was evaluated using soluble enzyme, enzyme-free supports, and immobilized catalysts. Enzyme immobilized in BGA reduced naringin and limonin concentrations by 54 and 100%, respectively, while the use of catalyst immobilized in OGA allowed a reduction of 74 and 76%, respectively, obtaining a final concentration of both bitter components under their detection threshold. The use of OGA biocatalyst presented better results than when soluble enzyme or enzyme-free support was utilized. Biocatalyst was successfully applied in juice debittering in five repeated batches.

Asunto(s)

Citrus paradisi , Limoninas , Adsorción , Estabilidad de Enzimas , Enzimas Inmovilizadas/química , Flavanonas , Hidrólisis , Complejos Multienzimáticos , Sefarosa , beta-Glucosidasa

RESUMEN

We analyzed the effect of naringin (NAR), a flavonoid from citric fruits, on bone quality and biomechanical properties, as well as the redox state of bone marrow in rats fed a fructose-rich diet (FRD), an experimental model to mimic human metabolic syndrome. NAR blocked the increase in the number of osteoclasts and adipocytes and the decrease in the number of osteocytes and osteocalcin (+) cells caused by FRD. Trabecular number was significantly higher in the FRD+NAR group. FRD induced a decrease in the femoral trabecular and cortical bone mineral density, which was blocked by NAR. The fracture and ultimate loads were also decreased in the FRD and FRD+NAR groups. NAR increased the number of nodes to terminal trabecula, the number of nodes to node trabecula, the number of nodes, and the number of nodes with 2 terminals and decreased the Dist (mean size of branches) value. FRD decreased bone marrow catalase activity, an effect that was prevented by NAR. In conclusion, FRD has detrimental effects on the long bones, which are associated with oxidative stress in the bone marrow. Most of these changes are prevented by NAR through its antioxidant properties and promotion of bone formation. Novelty: Fructose-rich diets have detrimental effects on long bones, which are associated with oxidative stress in the bone marrow. Most of these changes are prevented by naringin through its antioxidant properties and promotion of bone formation.

Asunto(s)

Fructosa , Síndrome Metabólico , Animales , Dieta , Flavanonas , Fructosa/efectos adversos , Síndrome Metabólico/prevención & control , Ratas , Ratas Wistar

RESUMEN

AIMS: To minimize fumonisins (FBs) accumulation by Fusarium verticillioides in post-harvest maize, using flavonoids obtained from citrus residues: naringin (NAR), neohesperidin (NEO), quercetin (QUER), and its mixtures. METHODS AND RESULTS: Response surface methodology with Box-Behnken design was applied in maize at 0.98 and 0.95 aw . The optimal mixture found, composed of 0.40 mmol kg-1  NAR, 0.16 mmol kg-1  NEO and 0.37 mmol kg-1 QUER, reduced the accumulation of FBs B1, B2, and B3 by 88 ± 6%, 90 ± 6% and 85 ± 5%, respectively, when applied to maize at 0.98 aw . The mentioned mixture led to a 54 ± 9% reduction of fumonisin B1 accumulation in maize adjusted to 0.95 aw . These flavonoids applied individually and as a mixture, affected the structure of both the cell wall and the cytoplasm of F. verticillioides. The cell wall lost rigidity and the cells appeared highly deformed, with ruptured plasmalemma and disrupted endomembranes. CONCLUSIONS: It was possible to diminish the accumulation of FBs in maize by a highly toxigenic Fusarium strain, producing severe damage to its ultrastructure. SIGNIFICANCE AND IMPACT OF STUDY: The results indicate the possible use of flavonoids from citrus industry residues as natural and environmentally friendly antifungal agents to restrain the accumulation of FBs in stored maize.

Asunto(s)

Citrus , Fumonisinas , Fusarium , Flavonoides/farmacología , Fusarium/química , Zea mays/microbiología

RESUMEN

Abstract Naringin has been shown to exhibit satisfying iron chelation capacity. Considering the side effects of routinely-used iron chelator (desferrioxamine, DFO), we decided to evaluate the iron chelation potency of naringin to discover whether or not it can be a promising natural substitute for treatment of excessive iron-related diseases. 35 mice were classified into five groups of 7 and subjected to iron dextran administration to induce the iron-overload condition. Iron-overloaded mice were then treated with normal saline (as control), naringin or DFO Morphology changes, and iron deposition in liver tissues were studied using H&E and Perl's staining. The results revealed that naringin is more potent than DFO in removing excessive iron ions deposited in liver tissues, indicating that naringin is a promising natural compound for therapy of iron overload disorders

Asunto(s)

Animales , Masculino , Ratones , Sobrecarga de Hierro/complicaciones , Flavanonas/análisis , Organización y Administración , Deferoxamina/efectos adversos

RESUMEN

Abstract Ischemia/reperfusion (IR) injury leads to overproduction of Reactive Oxygen Species (ROS), and disrupts membrane potential that contributes to cell death. The aim of this study was to determine if naringin (NAR), trimetazidine (TMZ) or their combination, protect the kidney mitochondrial from IR injury. Forty rats were randomly allocated into five groups, harboring eight rats each: Sham, IR, NAR (100 mg/kg), TMZ (5 mg/kg) and NAR plus TMZ. Ischemia was induced by obstructing both renal pedicles for 45 min, followed by reperfusion for 4 hours. The mitochondria were isolated to examine the ROS, Malondialdehyde (MDA), Glutathione (GSH), mitochondrial membrane potential (MMP) and mitochondrial viability (MTT). Our findings indicated that IR injury resulted in excessive ROS production, increased MDA levels and decreased GSH, MMP and MMT levels. However, NAR, TMZ or their combination reversed these changes. Interestingly, a higher protection was noted with the combination of both, compared to each drug alone. We speculate that this combination demonstrates a promising process for controlling renal failure, especially with the poor clinical outcome, acquired with NAR alone. This study revealed that pretreatment their combination serves as a promising compound against oxidative stress, leading to suppression of mitochondrial stress pathway and elevation of GSH level.

Asunto(s)

Animales , Masculino , Ratas , Trimetazidina/análisis , Flavanonas/análisis , Combinación de Medicamentos , Insuficiencia Renal/patología , Isquemia/patología , Preparaciones Farmacéuticas/administración & dosificación , Muerte Celular , Estrés Oxidativo , Mitocondrias/clasificación

RESUMEN

Naringin (Nar) has been reported to exert potential hepatoprotective effects against acetaminophen (APAP)-induced injury. Mitochondrial dysfunction plays an important role in APAP-induced liver injury. However, the protective mechanism of Nar against mitochondrial damage has not been elucidated. Therefore, the aim of this study was to investigate the hepatoprotective effects of Nar against APAP and the possible mechanisms of actions. Primary rat hepatocytes and HepG2 cells were utilized to establish an in vitro model of APAP-induced hepatotoxicity. The effect of APAP and Nar on cell viability was evaluated by a CCK8 assay and detection of the concentrations of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. The cellular concentrations of biomarkers of oxidative stress were measured by ELISA. The mRNA expression levels of APAP-related phase II enzymes were determined by real-time PCR. The protein levels of Nrf2, phospho (p)-AMPK/AMPK, and biomarkers of mitochondrial dynamics were determined by western blot analysis. The mitochondrial membrane potential (MMP) was measured by high-content analysis and confocal microscopy. JC-1 staining was performed to evaluate mitochondrial depolarization. Nar pretreatment notably prevented the marked APAP-induced hepatocyte injury, increases in oxidative stress marker expression, reductions in the expression of phase II enzymes, significant loss of MMP, mitochondrial depolarization, and mitochondrial fission in vitro. In conclusion, Nar alleviated APAP-induced hepatocyte and mitochondrial injury by activating the AMPK/Nrf2 pathway to reduce oxidative stress in vitro. Applying Nar for the treatment of APAP-induced liver injury might be promising.

RESUMEN

Resumo Fundamento: O núcleo do trato solitário (NTS) é uma área do cérebro que desempenha um papel fundamental na regulação renal e cardiovascular através dos impulsos dos barorreceptores. Objetivos: O objetivo deste estudo foi avaliar o efeito da Naringina (NAR) e trimetazidina (TMZ), isoladamente e combinadas, na atividade elétrica do NTS e na sensibilidade barorreflexa (SBR) na lesão de isquemia e reperfusão (I/R) renal. Métodos: Foram utilizados quarenta ratos machos Sprague-Dawley (200-250 g), alocados em 5 grupos com 8 ratos cada. Grupos: 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; e 5) TMZ5 + NAR100. A veia femoral esquerda foi canulada para infundir a solução salina ou droga e avaliar a SBR. A I/R foi induzida por oclusão dos pedículos renais por 45 min, seguida de reperfusão de 4 horas. O eletroencefalograma local do NTS foi registrado antes, durante a isquemia e durante a reperfusão. A fenilefrina foi injetada por via intravenosa para avaliar a SBR ao final do tempo de reperfusão. Os dados foram analisados por ANOVA de duas vias com medidas repetidas seguida pelo teste post hoc de Tukey. Um valor de p<0,05 foi considerado como significativo. Resultados: As ondas elétricas do NTS não se alteraram durante o tempo de isquemia, mas diminuíram significativamente durante todos os tempos de reperfusão. A atividade elétrica do NTS e a SBR foram reduzidas drasticamente em ratos com lesão I/R; no entanto, a administração de NAR e TMZ, isoladamente e combinadas, melhorou significativamente essas alterações em ratos com lesão I/R. Conclusões: Os resultados mostraram que a lesão de I/R leva à redução da atividade elétrica da SBR e do NTS, e pode haver uma ligação entre a I/R e a diminuição da SBR. Além disso, a NAR e a TMZ são agentes promissores para tratar complicações de I/R.

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Abstract Background: Nucleus tractus solitarius (NTS) is a brain area that plays a key role in kidney and cardiovascular regulation via baroreceptors impulses. Objectives: The aim of this study was to evaluate the effect of naringin (NAR) and trimetazidine (TMZ) alone and their combination on NTS electrical activity and baroreceptor sensitivity (BRS) in renal ischemia- reperfusion (I/R) injury. Methods: Forty male Sprague-Dawley rats (200- 250 g) were allocated into 5 groups with 8 in each. 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; and 5) TMZ5+ NAR100. The left femoral vein was cannulated to infuse saline solution or drug and the BRS was evaluated. I/R was induced by occlusion of renal pedicles for 45 min, followed by 4 hours of reperfusion. The NTS local electroencephalogram (EEG) was recorded before, during ischemia and throughout the reperfusion. Phenylephrine was injected intravenously to evaluate BRS at the end of reperfusion time. The data were analyzed by two-way repeated measurement ANOVA followed by Tukey's post hoc test. A p-value <0.05 was considered significant. Results: NTS electrical waves did not change during ischemia time, while they significantly decreased during the entire reperfusion time. NTS electrical activity and BRS dramatically reduced in rats with I/R injury; however, administration of NAR, TMZ alone or their combination significantly improved these changes in rats with I/R injury. Conclusions: The results showed that I/R injury leads to reduced BRS and NTS electrical activity and there may be an association between I/R and decreased BRS. In addition, NAR and TMZ are promising agents to treat I/R complications.

Asunto(s)

Animales , Masculino , Ratas , Trimetazidina/farmacología , Daño por Reperfusión/prevención & control , Daño por Reperfusión/tratamiento farmacológico , Ratas Sprague-Dawley , Núcleo Solitario , Barorreflejo , Flavanonas , Riñón

RESUMEN

ABSTRACT Objective: We aimed to research that naringin whether protects from renal ischemia/reperfusion induced renal damage in rats. Methods: Twenty-four Wistar albino female rats randomly were divided into three groups: 1) control group, in which the rats were only performed right nephrectomy; 2) a second group received right nephrectomy and left kidney ischemia (1 h) and reperfusion (24 h) group ischemia/reperfusion (I/R); 3) a third group received 50 mg/kg naringin orally once a day for two weeks before ischemia/reperfusion (I/R/N). Expression of cyclooxygenase-2 (COX-2), cytosolic phospholipase A2 (cPLA2), inducible nitric oxide synthase (iNOS), caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated x protein (Bax), serum creatinine (Cr), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) were measured by using enzyme-linked immunosorbent assay (ELISA). Results: Naringin-treated rats that performed renal ischemia/reperfusion demonstrated significant decrease in Cr, IL-6 and TNF-α levels when compared to the only renal ischemia/reperfusion performed rats. While renal ischemia/reperfusion caused a decrease of bcl-2 (1.72 ± 0.20 pg/ml) levels, while an increase of COX-2 (11882 ± 642 pg/ml), cPLA2 (2448 ± 139 pg/ml), iNOS (4331 ± 438 IU/ml), cleaved caspase-3 (7.33 ± 0.76 ng/ml) and Bax (2.33 ± 0.44 ng/ml) levels. The treatment of naringin reversed these kidney effects (7.47 ± 60.35 pg/ml; 9299 ± 327 pg/ml; 2001 ± 78 pg/ml; 3112 ± 220 IU/ml; 3.38 ± 0.54 ng/ml; 2.33 ± 0.44 ng/ml, respectively) (p <0.05). Conclusion: This study showed that naringin treatment attenuated renal damage induced by ischemia/reperfusion in rats.

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RESUMEN Objetivo: Nuestro objetivo fue investigar si la naringina protege del daño en los riñones provocado por isquemia-reperfusión renal en ratas. Material y métodos: De forma aleatoria, dividimos 24 ratas albinas Wistar hembras en tres grupos: 1) grupo control, en el que solo se les realizó a las ratas una nefrectomía derecha; 2) un segundo grupo isquemia-reperfusión, con nefrectomía derecha e isquemia de riñón izquierdo (1 h) y reperfusión (24 h); 3) un tercer grupo al que se le administró 50 mg/kg de naringina por vía oral una vez al día durante dos semanas antes de la isquemia-reperfusión. Por medio de un ensayo inmunoabsorbente ligado a enzimas (ELISA), se midieron las siguientes expresiones: ciclooxigenasa-2 (COX-2), fosfolipasa citosólica A2 (cPLA2), óxido nítrico sintetasa inducible (ONSi), caspasa-3, linfoma de células B2 (Bcl-2), proteína X asociada a Bcl-2 (Bax), creatinina sérica (Cr), factor de necrosis tumoral alfa (FNT-α) e interleucina 6 (IL-6). Resultados: Las ratas tratadas con naringina por isquemia-reperfusión renal mostraron un descenso significativo en los niveles de Cr, IL-6 y FNT-α en comparación con las ratas a las que se les indujo isquemia-reperfusión renal pero que no se les suministró naringina. La isquemia-reperfusión renal provocó un descenso de los niveles de Bcl-2 (1,72 ± 0,20 pg/ml) y un ascenso en los niveles de COX-2 (11882 ± 642 pg/ml), cPLA2 (2448 ± 139 pg/ml), ONSi (4331 ± 438 UI/ml), caspasa-3 escindida (7,33 ± 0,76 ng/ml) y Bax (2,33 ± 0.,44 ng/ml). El tratamiento con naringina diminuyó estos efectos en el riñón (7,47 ± 60,35 pg/ml; 9299 ± 327 pg/ml; 2001 ± 78 pg/ml; 3112 ± 220 UI/ml; 3.38 ± 0.54 ng/ml; 2.33 ± 0,44 ng/ml, respectivamente) (p <0,05). Conclusión: En este estudio se demostró que el tratamiento con naringina atenuó el daño renal producido por isquemia-reperfusión en ratas.

RESUMEN

Whey is a cheese co-product with high protein content used in the food industry due to its techno-functional properties and nutritive value. This study aims to optimize the production of ß-lactoglobulin (ß-lg) nanostructures, to characterize their techno-functional properties and stability, and to apply them as a carrier of bioactive molecules. Box-Behnken planning was applied to determine the best conditions to obtain the ß-lg nanostructure, which consists in treatment at 100 °C in NaCl 50 mmol·L-1 for 60 min. TEM analysis showed a fibril structure in the observed nanostructures. The nanostructured systems formed foam and emulsion with higher stability than the systems composed of the native protein. The results for encapsulation efficiency of bioactive compounds were 96.50%, 89.04%, 67.78%, and 36.39% for quercetin, rutin, naringin, and vitamin B2, respectively. Thus, ß-lg nanostructure's great capacity to encapsulate hydrophobic molecules was verified.

Asunto(s)

Lactoglobulinas/química , Nanoestructuras/química , Cápsulas , Queso , Interacciones Hidrofóbicas e Hidrofílicas

RESUMEN

BACKGROUND: Naringin (NAR) is a flavonoid enriched in several medicinal plants and fruits. An increasing interest in this molecule has emerged because it has the potential to contribute to alleviating many health problems. OBJECTIVE: This review briefly describes the NAR pharmacokinetics and it mainly focuses on the in vitro and in vivo animal studies showing NAR beneficial effects on cardiovascular, metabolic, neurological and pulmonary disorders and cancer. The anabolic effects of NAR on different models of bone and dental diseases are also analyzed. In addition, the evidence of the NAR action on the gastrointestinal tract is reported as well as its influence on the microbiota composition and activity. Finally, current research on NAR formulations and clinical applications are discussed. METHODS: The PubMed database was searched until 2019, using the keywords NAR, naringenin, cardiovascular and metabolic disorders, neurological and pulmonary disorders, cancer, bone and dental diseases, gastrointestinal tract, microbiota, NAR formulations, clinical trials. RESULTS: The number of studies related to the bioavailability and pharmacokinetics of NAR is limited. Positive effects of NAR have been reported on cardiovascular diseases, Type 2 Diabetes Mellitus (T2DM), metabolic syndrome, pulmonary disorders, neurodegenerative diseases, cancer, and gastrointestinal pathologies. The current NAR formulations seem to improve its bioavailability, which would allow its clinical applications. CONCLUSION: NAR is endowed with broad biological effects that could improve human health. Since a scarce number of clinical studies have been performed, the NAR use requires more investigation in order to know better their safety, efficacy, delivery, and bioavailability in humans.

Asunto(s)

Diabetes Mellitus Tipo 2 , Animales , Disponibilidad Biológica , Flavanonas , Flavonoides , Frutas , Humanos

RESUMEN

Plant growth promoting rhizobacteria (PGPR) is an alternative to chemical fertilizers for sustainable, environment friendly agriculture. There is a need to develop strategies to potentiate the interaction between rhizobacteria and plants. Flavonoids and organic acids (components of root exudates) play specific beneficial roles as carbon sources and signal molecules in the plant - rhizobacteria interactions. The goal of this work is to encapsulate signal molecules, namely citric acid and naringin, an organic acid and a flavonoid, respectively, by a biodegradable polymer, polycaprolactone (PCL), in order to maintain the stability and activity of those signal molecules and enable their slow or controlled release over a selected period of time, according to the needs of the plants. This approach is expected to potentiate food crops, namely peanut crop, in adverse environmental conditions (water deficit), by promoting the beneficial interaction between the peanut plant (A. hypogaea) and rhizobacteria. The microcapsules (MCs) are obtained by an emulsion process combined with solvent evaporation technique and are characterized by scanning electron microscopy, thermogravimetry and Fourier transformed infrared spectroscopy. The kinetics of in vitro release of encapsulated molecules, in a period where the uptake of the compound in plants can occur, is studied. The encapsulation synthesis parameters that lead to the best encapsulation process yield and efficiency, as well as to the best final performance in terms of release, are identified. The effect of pH and molecular weight of PCL is found to mediate the release properties of the molecules for different types of soil. PCL 45000 Mw dissolved at 16% in dichloromethane leads to an encapsulation efficiency of 75% and the resulting MCs containing naringin exhibit a slow release profile for 30 days, unmodified by pH, enabling their use in soils of different characteristics. This research makes possible the manufacturing of smart materials for sustainable agriculture practices.

Asunto(s)

Agricultura/métodos , Ácido Cítrico/análisis , Monitoreo del Ambiente , Poliésteres/análisis , Microbiología del Suelo , Cápsulas , Fertilizantes , Desarrollo de la Planta

RESUMEN

Lactoferrin (LF) is a glycoprotein that serves as a potential vehicle for small bioactive molecules in food. In an effort to improve this functionality, the kinetic and thermodynamic interaction of LF with naringin (NR) was studied by surface plasmon resonance (SPR). The results demonstrated that the association rate constant between LF and NR was 5.00 × 104 M-1 s-1, while the dissociation rate of the complex was 0.36 s-1, at 25 °C. The stable complex predominated over free molecules (ΔG25°C0=-29.35 kJ mol-1), and the binding constant was 1.39 × 105 M-1, at 25 °C. The association of LF and NR to form an intermediate complex occurred in multi-steps. Nevertheless, the intermediate complex formation from the dissociation of the stable complex occurred in a single step with the activation energy independent of temperature. This study provides an important basis to explore LF as a vehicle for bioactive molecules.

Asunto(s)

Flavanonas/química , Lactoferrina/química , Resonancia por Plasmón de Superficie , Animales , Bovinos , Flavanonas/metabolismo , Cinética , Lactoferrina/metabolismo , Unión Proteica , Temperatura , Termodinámica

RESUMEN

Brazilian native fruits (BNF) remain unexplored and underutilized resources with a high potential to improve human health and wellness. In our study, five new BNF (Eugenia stipitata, Sageretia elegans, Byrsonima arthropoda, Spondias mombin andRubus rosaefolius)were evaluated for their phenolic composition by LC-ESI-QTOF-MS; and for their ROS and RNS scavenging effects (ROO, O2-, NO, HOCl); in vivo anti-inflammatory activity (neutrophil migration); and in vivo acute toxicity in Galleria mellonella. Eighty-six phenolic compounds were identified, including hydroxybenzoic acids, hydroxycinnamic acids, flavonoids, anthocyanins and ellagitannins, several of which had never been reported in BNF. The BNF exhibited high antioxidant effects against biologically relevant radicals, and treated animals showed decreased neutrophil influx and NF-kB activation. Thus, these BNF are good sources of antioxidant and anti-inflammatory molecules that can be beneficial for human health as functional foods. Based on their bioactivity, they can be considered as new Brazilian superfruits.

Asunto(s)

Antiinflamatorios/farmacología , Frutas/química , Fenoles/farmacología , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Antocianinas/análisis , Antocianinas/farmacología , Antiinflamatorios/análisis , Antioxidantes/análisis , Antioxidantes/farmacología , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cromatografía Liquida , Ácidos Cumáricos/análisis , Ácidos Cumáricos/farmacología , Flavonoides/análisis , Flavonoides/farmacología , Alimentos Funcionales , Taninos Hidrolizables/análisis , Taninos Hidrolizables/farmacología , Hidroxibenzoatos/análisis , Hidroxibenzoatos/farmacología , Lepidópteros/efectos de los fármacos , Lepidópteros/metabolismo , Espectrometría de Masas , Ratones , FN-kappa B/genética , FN-kappa B/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Fenoles/análisis , Extractos Vegetales/análisis , Extractos Vegetales/farmacología , Células RAW 264.7 , Pruebas de Toxicidad Aguda

RESUMEN

Glutathione (GSH) is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca2+ absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K3, sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca2+ absorption. The GSH depleting drugs switch the redox state towards an oxidant condition provoking oxidative/nitrosative stress and inflammation, which lead to apoptosis and/or autophagy of the enterocytes. Either the transcellular Ca2+ transport or the paracellular Ca2+ route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca2+ pathway are decreased. The flavonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca2+ absorption, not only by restoration of the GSH levels in the intestine but also by their anti-apoptotic properties. Ursodeoxycholic acid, melatonin and glutamine also block the inhibition of Ca2+ transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca2+ absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety, pharmacokinetics and pharmacodynamics of them.

Asunto(s)

Antimetabolitos/efectos adversos , Antioxidantes/farmacología , Calcio/metabolismo , Glutatión/antagonistas & inhibidores , Absorción Intestinal/efectos de los fármacos , Antimetabolitos/farmacocinética , Glutatión/metabolismo , Humanos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Oxidantes/efectos adversos , Oxidantes/farmacocinética

RESUMEN

The aim of this study was to evaluate whether NAR has a hepatoprotective role in a model of STZ-induced diabetes and to elucidate the underlying mechanisms triggered by the flavonoid. Male Wistar rats were divided into three groups: 1) controls, 2) STZ rats 3) STZ rats treated daily with NAR (40 mg/kg b.w.) for 30 days. NAR prevented increases in serum aminotransferases and alkaline phosphatase activities in STZ rats. The flavonoid blocked serum lipid alterations, but not the biometric parameters in STZ rats. Microscopic examination in liver from STZ rats revealed morphological changes indicative of increased adipogenesis and cell death and inflammation, which were all mitigated by the flavonoid. NAR inhibited the NFκB/IL-6/Cox-2 overexpressions triggered by oxidative stress in STZ rats. The iNOS/NO/nitrosylated protein pathway was also blocked by NAR. The increment in the protein expression of Fas/FasL/caspase-3 and in the Bax/Bcl-2 ratio showed that both pathways of apoptosis were increased by the diabetes, effects that were abrogated by NAR treatment. In conclusion, NAR protects against the liver damage caused by STZ-induced diabetes and it could be a novel therapeutic strategy to prevent the non alcoholic fatty liver disease associated with the type 1Diabetes mellitus.

Asunto(s)

Antioxidantes/farmacología , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 1/patología , Flavanonas/farmacología , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Hígado/metabolismo , Hígado/patología , Pruebas de Función Hepática , Masculino , Estrés Nitrosativo/efectos de los fármacos , Ratas Wistar , Estreptozocina