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Introduction: acute myocardial infarction (AMI) remains with high morbidity and mortality rates and occurs mainly due to reduced blood flow due to atherosclerotic plaque leading to ischemia. Although reperfusion is the main clinical intervention, it exacerbates damage initiated during ischemia. Therefore, natural products have been studied for the prevention and treatment of AMI. Naringin (NRG) is a flavonoid found in citrus fruits with recognized cardioprotection against atherosclerosis, coronary disease, hypertension, cardiac hypertrophy, AMI and ischemic stroke. Objective: to elucidate the mechanism of NRG in cardioprotection against IR injury. Methods: in isolated hearts of Wistar rats, the effects of NRG (5 and 10 µM) on contractile and electrocardiographic variables were evaluated. Isolated hearts were perfused with NRG (5 µM) or NRG with glibenclamide (GLI, 10 µM, a non-specific blocker of KATP channels) and subjected to global ischemia (30 min) and reperfusion (60 min). The area of infarction, tissue injury through the release of lactate dehydrogenase (LDH), index and occurrence of arrhythmias and contractile variables were evaluated. In animals pre-treated for 7 days (NRG 25 mg/kg or N-acetyl cysteine 100 mg/kg) and submitted to the IR protocol, the expression of Bax, Blc-2, SOD CuZn and SOD Mn were evaluated. In addition, citrate synthase activity and histological changes were analyzed. Results: When NRG was perfused at 5 or 10 µM concentrations, it did not change contractile and electrocardiographic variables in isolated hearts. The cardioprotective effect of NRG (5 µM) was abolished in the presence of GLI, since there was a decrease in LVDP, an increase in tissue injury (LDH) and infarcted area, an increase in the rate of arrhythmias and in the occurrence of more severe arrhythmias (tachycardia and ventricular fibrillation). In animals treated with NRG and submitted to IR, there was a decrease in Bax expression and in the Bax/Bcl-2 ratio compared to the vehicle + IR group. There was no alteration in the expression of SOD CuZn and SOD Mn among the four groups studied, in addition, in the hearts of animals pre-treated with NRG there was an increase in citrate synthase activity. Histopathological analysis showed that NRG decreased intracellular and interstitial edema and prevented changes in nuclear and cytoplasmic diameter. Conclusion: this study demonstrates that NRG has a cardioprotective effect against cardiac IR injury mediated by its anti-apoptotic, antiarrhythmic action and probable activation of KATP. In addition, it provides subsidies for future studies that can ensure the use of medicinal plants, natural products and foods rich in NRG in cardioprotection against AMI. Introdução: o infarto agudo do miocárdio (IAM) permanece com altas taxas de morbimortalidade e ocorre, principalmente, por redução do fluxo sanguíneo em virtude de placa de ateroma levando à isquemia. Embora a reperfusão seja a principal intervenção na clínica, ela exacerba os danos iniciados durante a isquemia. Sendo assim, produtos naturais tem sido alvo de estudo para prevenção e tratamento do IAM. A naringina (NRG) é um flavonoide encontrado em frutas cítricas com reconhecida cardioproteção contra aterosclerose, doença coronariana, hipertensão, hipertrofia cardíaca, IAM e acidente vascular cerebral isquêmico. Objetivo: elucidar os mecanismos da NRG na cardioproteção frente à injúria de IR. Métodos: em coração isolado de ratos Wistar foram avaliados os efeitos da NRG (5 e 10 µM) sobre variáveis contráteis e eletrocardiogáficas. Corações isolados foram perfundidos com NRG (5 µM) ou NRG com glibenclamida (GLI, 10 µM, um bloqueador não-específico dos canais KATP) e submetidos a isquemia global (30 min) e reperfusão (60 min). Foram avaliados área de infarto, lesão tecidual por meio da liberação da lactato desidrogenase (LDH), índice e ocorrência de arritmias e variáveis contráteis. Em animais pré-tratados por 7 dias (NRG 25 mg/kg ou N-acetil cisteína 100 mg/kg) e, submetidos ao protocolo de IR, foram avaliados a expressão da Bax, Blc-2, SOD CuZn e SOD Mn. Além disso, analizou-se a atividade da citrato sintase e alterações histológicas. Resultados: A NRG quando perfundida nas concentrações de 5 e 10 µM não alterou as variáveis contráteis e eletrocardiográficas em coração isolado. O efeito cardioprotetor da NRG (5 µM) foi abolido na presença de GLI, uma vez que houve diminuição da PDVE, aumento da injúria tecidual (LDH) e área de infarto, aumento do índice de arritmias e da ocorrência de arritmias mais graves (taquicardia e fibrilação ventricular). Nos animais tratados com a NRG e submetidos a IR, houve diminuição da expressão da Bax e da razão Bax/Bcl-2 em comparação ao grupo veículo + IR. Não houve alteração da expressão da SOD CuZn e SOD Mn entre os quatro grupos estudados, além disso, nos corações dos animais pré-tratados com a NRG houve um aumento da atividade da citrato sintase. A análise histopatológica mostrou que a NRG diminuiu o edema intracelular e intersticial e preveniu alterações no diâmetro nuclear e citoplasmático. Conclusão: este estudo demonstra que a NRG possui efeito cardioprotetor contra a injúria de IR cardíaca mediada por sua ação antiapoptótica, antiarrítmica e provável ativação de KATP. Além disso, fornece subsídios para futuros estudos que possam assegurar o uso de plantas medicinais, produtos naturais e alimentos ricos em NRG na cardioproteção contra o IAM. São Cristóvão

Introduction: Urothelial carcinoma is a significant public health problem. Transitional cell carcinoma (TCC) is the most common subtype, accounting for approximately 90 % of all bladder cancers. Chemotherapeutic protocols have been studied, but some present high toxicity and low tolerability. Naringin is a polyphenolic compound found mainly in citrus fruits, which antitumor activity has been studied in several types of cancer. However, there is little information about naringin effects on bladder cancer. This study aimed to evaluate the antitumor potential of naringin in silico and in vitro using two bladder cancer cell lines Method: In silico analysis was carried out by PASS Online software. In vitro, the effects of naringin treatment (12.5 - 400 µM) were evaluated regarding its cytotoxicity, clonogenic survival, morphological alterations, cell cycle progression, migration, and mutagenicity Results: In silico analyses predicted antitumor activity through several mechanisms of action. In vitro results showed naringin presented cytotoxic effects, reduced the number of colonies, inhibited cell migration, and changed the morphology and cell cycle progression of the two cell lines evaluated. However, naringin did not present mutagenic effects. Conclusions: Naringin has antiproliferative activity and is a promising candidate for bladder cancer treatment., Introducción: el carcinoma urotelial es un problema de salud pública importante. El carcinoma de células de transición es el subtipo más común y representa aproximadamente el 90 % de todos los cánceres de vejiga. Se han estudiado protocolos quimioterapéuticos, pero algunos presentan alta toxicidad y baja tolerabilidad. La naringina es un compuesto polifenólico que se encuentra principalmente en los cítricos, cuya actividad antitumoral se ha estudiado en varios tipos de cáncer. Sin embargo, hay poca información sobre los efectos de la naringina en el cáncer de vejiga. Este estudio tuvo como objetivo evaluar el potencial antitumoral de la naringina in silico e in vitro utilizando dos líneas celulares de cáncer de vejiga. Método: el análisis in silico se llevó a cabo mediante el software PASS Online. In vitro, se evaluaron los efectos del tratamiento con naringina (12,5 - 400 µM) en cuanto a su citotoxicidad, supervivencia clonogénica, alteraciones morfológicas, progresión del ciclo celular, migración y mutagenicidad. Resultados: los análisis in silico predijeron la actividad antitumoral a través de varios mecanismos de acción. Los resultados in vitro mostraron que la naringina presentó efectos citotóxicos, redujo el número de colonias, inhibió la migración celular y cambió la morfología y la progresión del ciclo celular de las dos líneas celulares evaluadas. Sin embargo, la naringina no presentó efectos mutagénicos. Conclusiones: la naringina tiene actividad antiproliferativa y es un candidato prometedor para el tratamiento del cáncer de vejiga., Conselho Nacional de Desenvolvimento Científico e Tecnológico, grant number CNPq 310905/2020-6 (CNPq Research Productivity Scholarship), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Finance code 001), Universidade Federal de Ouro Preto, grant number 23109.000928/2020-33

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

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

Fig. 1 Estructura general de los flavonoides y el sistema de numeración empleado para su nomenclatura, Fig. 2 Subclases de flavonoides, Fig. 3 Rutas generales de biosíntesis de fenilpropanoides y flavonoides, Fig. 4 Estructura de la hesperidina glicosilada, Fig. 5 Ruta sintética resumida de los flavonoides en los cítricos, Fig. 6. Estructura de la naringina, Fig 7. Estructura de la Nobiletina Se ha identificado que en Colombia se emplea la infusión del exocarpio o cascara de mandarina (Citrus reticulata Var Arrayana) para el control de la diabetes como un tratamiento de medicina alternativa para el manejo de esta condición. Generalmente se ha atribuido el efecto benéfico del consumo de esta infusión a la presencia de flavonoides en este tejido de los frutos, sin embargo, no se han realizado estudios sistemáticos para identificar la presencia de flavonoides y su relación con el control de la diabetes en el país. Esta monografía surge como respuesta a la necesidad de establecer un marco de referencia para el desarrollo de posteriores investigaciones con base a las experiencias reportadas por autores alrededor del mundo que han realizado investigaciones sobre Citrus reticulata y otras especies del género Citrus. La metodología seguida para el desarrollo del presente trabajo consistió en la identificación de palabras clave de búsqueda, su consulta en diferentes bases de datos de revistas indexadas, el filtrado y clasificación de los artículos y materiales bibliográficos encontrados y la organización de la información sobre tres ejes básicos; las características del género Citrus y de la especie Citrus reticulata, los avances en la identificación de las rutas de biosíntesis de flavonoides haciendo énfasis en los estudios sobre la síntesis de flavonoides en cítricos y estudios sobre la relación entre flavonoides identificados en el exocarpio de frutos cítricos y el manejo de la diabetes. Se encontró una gran cantidad de información sobre las características físicas, químicas y biológicas de las muchas variedades de Citrus reticulata que se han identificado en el mundo, de las cuales se escogieron las variedades con mayor mercado para analizar sus características. Con respecto a la biosíntesis de flavonoides se identificó que ha habido avances importantes en la identificación de las rutas metabólicas relacionadas con los flavonoides, tanto en la identificación de enzimas y pasos clave como en la relación de ciertos genes en la síntesis de distintos flavonoides. Igualmente, se lograron identificar artículos de investigación que reportan resultados sobre el efecto de flavonoides aislados de frutas cítricas en una amplia variedad de condiciones que afectan la salud humana, desde problemas de circulación, normalización y manejo de niveles de azúcar y lípidos, capacidad anticancerígena hasta síndromes metabólicos, lo que aumenta el espectro de posibles aplicaciones de estas moléculas en farmacología. It has been identified that in Colombia the infusion of the exocarp or mandarin peel (Citrus reticulata Var Arrayana) is used for the control of diabetes as an alternative medicine treatment for the management of this condition. Generally, the beneficial effect of the consumption of this infusion has been attributed to the presence of flavonoids in this fruit tissue, however, no systematic studies have been conducted to identify the presence of flavonoids and their relationship with diabetes control in the country. This monograph response to the need to establish a framework of reference for the development investigations based on the experiences reported by authors around the world who have studied the Citrus reticulata and other species of the genus Citrus. The methodology followed in this work consist of the identification of key words, their search in different indexed journals databases, filtering and classification the articles and bibliographic materials found and organization of the information on three basic axes; the characteristics of the genus Citrus and the species Citrus reticulata, the advances in the identification of flavonoid biosynthesis routes with emphasis on studies on the synthesis of flavonoids in citrus fruits and studies on the relationship between flavonoids identified in the exocarp of citrus fruits and the management of diabetes. A large amount of information was found on the physical, chemical, and biological characteristics of the many varieties of Citrus reticulata that have been identified in the world, from which the varieties with the largest market were chosen to analyze their characteristics. With respect to flavonoid biosynthesis, it was identified that there have been important advances in the identification of the metabolic pathways related to flavonoids, both in the identification of enzymes and key steps and in the relationship of certain genes in the synthesis of different flavonoids. In addition, research articles were identified that report results on the effect of flavonoids isolated from citrus fruits on a wide variety of conditions that affect human health, from circulation problems, normalization and management of sugar and lipid levels, anticarcinogenic capacity to metabolic syndromes, which broadens the spectrum of possible applications of these molecules in pharmacology.

RESUMEN Introducción La naringina es un flavonoide utilizado como suplemento alimenticio, el cual es comercializado en productos para atletas, se promueve como: potenciador de otros suplementos, aumenta la capacidad física y como “quemador de grasa” para la pérdida de peso, entre otros efectos. Objetivo: Evaluar la evidencia disponible del efecto de la suplementación oral de naringina en combinación con actividad física y/o ejercicio en respuestas clínicas en comparación con sólo actividad física y ejercicio. Material y Métodos Se realizó una búsqueda sistemática en bases de datos electrónicas. Fuentes de datos: Science Direct, MEDLINE, PubMed, Web of Science, Registro Cochrane Central de ensayos controlados, SPORTDiscus. Selección de estudios: Publicaciones con el objetivo de estudiar los efectos de la naringina en combinación con ejercicio o actividad física. Extracción de datos y método de síntesis: Se realizó analisis por dos revisores, datos extraídos: autores, año de publicación, diseño del estudio, universo de estudio, intervención y resultados relevantes; se cuantificó la calidad con la escala PEDro. La revisión fue realizada siguiendo los lineamientos PRISMA. Resultados Se identificaron 3 ensayos clínicos (escala de PEDro media de 8,3). Naringina mejora el tiempo de actividad física y disminuye el tiempo fatiga, y mejora subjetivamente la condición física pero no resultó estadísticamente mejor al placebo. Conclusiones Los estudios muestran contradicciones sobre los efectos de la combinación sobre la condición física. ABSTRACT Introduction Naringin is a flavonoid used as a dietary supplement, which is marketed in products for athletes, is promoted as enhancer of other supplements, increases physical capacity and as a “fat burner” for weight loss, among other effects. Objective: To evaluate the available evidence of the effect of oral naringin supplementation in combination with physical activity and / or exercise on clinical responses compared with physical activity and exercise alone. Material and Method A systematic search was carried out in electronic databases. Data sources were Science Direct, MEDLINE, PubMed, Web of Science, Cochrane Central Register of Controlled Trials, SPORTDiscus. Selection of studies was publications aiming to study the effects of naringin in combination with exercise or physical activity. Data extraction and synthesis method: Two reviewers analyzed data; data extracted: authors, year of publication, study design, universe of study, intervention and relevant results; quality was quantified with the PEDro scale. The review was carried out following the PRISMA guidelines. Results Three clinical trials were identified (mean PEDro score of 8.3). Naringin improves physical activity time and decreases fatigue time, and subjectively improves physical condition but was not statistically better than placebo. Conclusions Studies show contradictions about the effects of the combination on physical fitness.

Cardiac ischemia-reperfusion (IR) injury leads to a decrease in myocardial oxygen supply and irreversible damage of heart. Reperfusion of artery is necessary to restore blood flow of heart, however, it may amplify myocardial injury. Studies have shown that natural compounds with antioxidant activity can minimize injury caused by IR injury. Then, naringin (NGR) is a flavonoid with antioxidant and anti-inflammatory activities and that reduces the risk of atherosclerosis. The aim of the study was to evaluate the cardioprotective effects of pre-treatment with NGR in hearts submitted to IR lesion. For this, male Wistar rats (N=60) were divided into 4 groups and pre-treated orally for 7 days: 1) Control (0.9% saline solution + 25% DMSO) without IR injury; 2) Vehicle + IR (0.9% saline + 25% DMSO) submitted to IR, 3) NGR + IR (0.9% saline + 25% DMSO + 25 mg/kg NGR) and 4) NAC + 9% + DMSO 25% + N-acetyl cysteine (NAC) 100 mg/kg). After the treatments, the hearts were mounted in Langendorff type retrograde perfusion system (constant flow 8 ml/min, 37oC) and subjected to global ischemia (30 min) followed by 60 min reperfusion. In all experimental groups, the electrocardiographic parameters (PRi, QTc, QRS and heart rate) (n=7) and contractile (left ventricular pressure developed), derived of contraction (+ dP/dt) and relaxation (-dP/dt) (n=10). Coronary pressure (CP), arrhythmia score, and lactate dehydrogenase (LDH) in the perfusate (n=5) were also evaluated. The evaluation of the oxidative stress of hearts was made based on the determination of the production of reactive oxygen species, lipid peroxidation (TBARS), catalase (CAT) and superoxide dismutase (SOD), total sulfhydryl groups (SH) and protein carbolation. The results showed that pre-treatment of the animals with NGR was able to restore the reduction of PDVE, + dP/dt and -dP/dt induced by IR. Similar result to NGR was also observed in the group treated with NAC. The heart rate was increased in NGR-treated animals when compared to vehicle+IR group. There was no significant difference in relation to CP between the experimental groups studied. Furthermore, on the electrocardiogram, it was not possible to detect T wave inversion and ST segment elevation in the hearts of animals treated with NGR. No change was observed in the PRi, QTc intervals and duration of the QRS complex between the experimental groups (n=7). Pretreatment of the animals with NGR attenuated the severity of the arrhythmias, decreasing the arrhythmia score from 21.4  2.48 a.u. (vehicle + IR) to 5.5  0.72 a.u. (NGR) associated to a decrease in the occurrence of more severe arrhythmias such as ventricular fibrillation. The results showed a reduction of 78% of LDH in the perfusate of animals pretreated with NGR, associated with a reduction of the infarct area to 10% when compared to vehicle+IR group (47%) (p< 0.05). The results show an increase in ROS production in the vehicle + IR group (1.61  0.30 a.u, p

Submitted by MARCIA ROVADOSCHI (marciar@unifra.br) on 2018-08-20T12:34:53Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_CarlaFontouraFerrreira.pdf: 19008440 bytes, checksum: b5b118a8e2abb810388a00dc8e27ac80 (MD5) Made available in DSpace on 2018-08-20T12:34:53Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_CarlaFontouraFerrreira.pdf: 19008440 bytes, checksum: b5b118a8e2abb810388a00dc8e27ac80 (MD5) Previous issue date: 2017-03-30 Reactive species (ERs) and oxidative stress contribute to the pathophysiology of several diseases including dementia. An innovative alternative for protecting organs such as the brain is the use of antioxidant-like flavonoids such as naringin and naringenin. However, these two compounds have low bioavailability when administered orally. An alternative to overcome this limitation is the use of nanocarriers, such as nanocapsules (NC). Therefore, the present study aimed to evaluate the neuroprotective effect of naringin and naringenin in a model of streptozotocin (STZ) -induced dementia in mice. The profile of drug release from in vitro suspensions was evaluated as well as the effects of nanoencapsulated drugs on cell viability with Vero cell line. In addition, the involvement of oxidative stress in the brain tissue of mice was verified. Naringin and naringenin NC had acid pH, particle diameter less than 95 nm, polydispersity index (IPD) of less than 0.2. The zeta potential was negative, between -12.46 and -17.6 mV, and the encapsulation efficiency was 93% for naringin and 95% for naringenin. For the study of the release profile, the dialysis technique was used, with 46.5% of naringin and 6.9% of naringenin being released in the medium, in a period of 9h. The results of the cell viability assay showed that the NC suspensions caused a reduction in cell viability of Vero cells at concentrations of 5, 50 and 500 μg / ml when compared to the control at the 24 and 72h incubation periods. For in vivo evaluation of neuroprotection the mice were pretreated for 15 days by oral (vo) with the suspension of white nanocapsules (NB), NC containing the mixture naringin and naringenin (N-NANG), suspension of naringin and naringenin in the form Free (NANG) and vehicle (Sham) at dose 10 mg / kg body weight. Subsequently, stereotactic surgery was performed for intracerebroventricular (i.c.v) infusion of STZ or FAC (cerebral artificial fluid). Behavioral tasks were then initiated. In the open field task the locomotor activity differed in the test section in the NB + STZ group evidenced by a hyperlocomotion between the mice of this experimental group. For exploratory activity there was no significant difference between groups. In the evaluation of the short-term memory in the task of object recognition the animals treated with N-NANG did not recognize the new object. For the long-term memory there was learning only for the mice treated with NB. The mice treated with NB + STZ had memory impairment assessed in the task of inhibitory avoidance, and pre-treatment with N-NANG prevented this effect. In the evaluation of the anti-depressive and anxiolytic-type effects, it was observed that the NNANG + STZ induced greater body activity in the twist parameter in the tail suspension task and in the high "zero" labyrinth there was an increase in the number of spies Relative to the free drug. Regarding the levels of brain antioxidants, there were no changes in the levels of reduced glutathione (GSH) and catalase activity (CAT). The NB + STZ group significantly increased levels of brain lipid peroxidation of thiobarbituric acid reactive species (TBA). N-NANG administration reduced the peroxidation induced by STZ. Thus, it can be concluded that the CNs present characteristics suitable for oral administration. In vivo studies demonstrate that pre-treatment with naringin and naringenin NC was preventative and able to reverse memory deficits, type-depressive and anxiolytic behavior caused by STZ in mice. However, this preventive effect was not observed with the flavonoids in the free form. As espécies reativas (ERs) e o estresse oxidativo contribuem para a fisiopatologia de diversas doenças entre elas a demência. Uma alternativa inovadora de proteção aos órgãos como o cérebro é o uso de flavonoides com ação antioxidante como a naringina e naringenina. No entanto, esses dois compostos apresentam baixa biodisponibilidade quando administrados pela via oral. Uma alternativa para contornar esta limitação é o uso de nanocarreadores, como as nanocápsulas (NC). Diante disso, o presente estudo teve por objetivo avaliar o efeito neuroprotetor de NC contendo naringina e naringenina em modelo de demência induzida por estreptozotocina (STZ) em camundongos. Foram avaliados o perfil de liberação dos fármacos a partir das suspensões in vitro assim como determinados os efeitos dos fármacos nanoencapsulados na viabilidade celular com linhagem de células Vero. Além disso, foi verificado o envolvimento do estresse oxidativo no tecido cerebral dos camundongos. As NC de naringina e naringenina apresentaram pH ácido, diâmetro de partícula inferior a 95 nm, índice de polidispersão (IPD) menor que 0,2. O potencial zeta foi negativo, entre -12,46 e -17,6 mV e a eficiência de encapsulação foi de 93% para naringina e 95% para a naringenina. Para o estudo do perfil de liberação, foi empregada a técnica de diálise, sendo que 46,5% da naringina e 6,9% da naringenina foram liberadas no meio, em um período de 9h. Os resultados do ensaio de viabilidade celular mostraram que as suspensões de NC causaram redução da viabilidade celular das células Vero nas concentrações de 5, 50 e 500 μg/mL quando comparadas ao controle nos períodos de 24 e 72h de incubação. Para avaliação in vivo da neuroproteção os camundongos foram pré-tratados durante 15 dias via oral (v.o) com a suspensão de nanocápsulas brancas (NB), NC contendo a mistura naringina e naringenina (N-NANG), suspensão de naringina e naringenina na forma livre (NANG) e veículo (Sham) na dose 10 mg/kg corporal. Subsequentemente foi realizada a cirurgia estereotáxica para a infusão via intracerebroventricular (i.c.v) de STZ ou FAC (fluido artificial cerebral). Posteriormente foram iniciadas as tarefas comportamentais. Na tarefa do campo aberto a atividade locomotora diferiu na seção teste no grupo NB+STZ evidenciada por uma hiperlocomoção entre os camundongos deste grupo experimental. Para atividade exploratória não houve diferença significativa entre os grupos. Na avaliação da memória de curto prazo na tarefa de reconhecimento de objetos os animais tratados com N-NANG não reconheceram o objeto novo. Para a memória de longo prazo houve aprendizagem somente para os camundongos tratados com NB. Os camundongos tratados com NB+STZ tiveram prejuízo de memória avaliado na tarefa da esquiva inibitória, e o pré-tratamento com N-NANG preveniu esse efeito. Na avaliação do efeito tipo anti-depressivo e tipo-ansiolítico observa-se que as N-NANG+STZ induziram maior atividade corporal no parâmetro torções na tarefa da suspensão da cauda e no labirinto em “zero” elevado houve um aumento do número de espiadas em relação ao fármaco livre. Com relação aos níveis de antioxidantes cerebrais não houve alterações nos níveis de Glutationa reduzida (GSH) e na atividade da catalase (CAT). O grupo NB+STZ aumentou significativamente os níveis de peroxidação lipídica cerebral de espécies reativas ao ácido tiobarbitúrico (TBA). Já administração de N-NANG reduziu a peroxidação induzida pela STZ. Com isso pode-se concluir que as NC apresentam características adequadas para administração via oral. Os estudos in vivo demonstram que o pré- tratamento com as NC de naringina e naringenina foi preventivo e capaz de reverter os déficits de memória, comportamento tipo-depressivo e ansiolítico causado pela STZ nos camundongos. Contudo, esse efeito preventivo não foi observado com os flavonoides na forma livre.

O objetivo deste estudo foi avaliar o efeito de diferentes doses de baicaleína, morina, naringenina, naringina, quercetina e rutina no aumento dos níveis de colesterol-HDL e trigliceróis em ratos hiperlipidêmicos. Tais flavonóides foram administrados em 3 doses (5, 10, 15 mg/animal) a ratos machos da raça Wistar, com 30 dias de vida, alimentados com dieta não purificada de fórmula da marca Labina®. A hiperlipidemia foi induzida pela administração de Triton, na dose de 300 mg/kg de peso vivo. Após 24 horas, os flavonóides foram administrados, sendo cada dose aplicada em grupos de 8 animais. Após 48 horas da aplicação do Triton, os animais foram anestesiados e, por punção cardíaca, amostras de sangue foram coletadas para realização das análises de colesterol, colesterol-HDL e triacilgliceróis no soro. Os melhores resultados para a redução do colesterol foram obtidos com os flavonóides quercetina e rutina, na dose de 5 mg, e naringenina, na dose de 10 mg. A baicaleína, nas doses de 5 e 10 mg, foi a que apresentou as menores reduções para colesterol-HDL. Já para as concentrações de triacilgliceróis, a baicaleína foi a que mais reduziu este parâmetro, independentemente da dose utilizada. The objective of this study was to evaluate the effect of different doses of baicalein, morin, naringenin, naringin, quercetin and rutin on the increase of HDL cholesterol and triglycerols levels in hyperlipidemic rats. These flavonoids were administered in three doses (5, 10, 15 mg/animal) to male rats of the Wistar strain, with 30 days of life, fed non-purified diet of formula Labina®. The hyperlipidemia was induced by the administration of Triton, in the dose of 300 mg/kg of rat body weight. After 24 hours, the flavonoids were administered, each dose applied in groups of 8 animals. After 48 hours of Triton application, the animals were anesthetized and samples of blood were collected, by heart puncture, in order to determine cholesterol, cholesterol-HDL and triacylglycerols in the serum. The best results in the reduction of the cholesterol were obtained with quercetin and rutin, in the dose of 5.mg, and naringenin, in the dose of 10 mg. Baicalein in the doses of 5 and 10 mg, showed the best responses for cholesterol-HDL. For triacylglycerols, baicalein also presented the best effects, independently of the dose applied.

e realizó el estudio comparativo de distintas técnicas extractivas de naringina utilizando cáscaras de pomelo (Citrus paradisi). Las mejores condiciones de preparación previa del material son el fragmentado de cáscara fresca y el secado en estufa con posterior fragmentado. Para cáscara fresca resulta más conveniente la extracción con etanol puro por Soxhlet (obteniéndose 26g/kg de peso fresco), mientras que para cáscara seca los mejores resultados se obtienen en la extracción con la mezcla etanol-agua en las proporciones 70:30 por maceración (20g/kg de peso fresco) y reflujo (22g/kg de peso fresco). Se observaron evidencias de la importancia del agua en el proceso de extracción. Se determinaron los valores de concentración de naringina en cáscaras de distintas variedades de Citrus paradisi de la región del Noroeste Argentino. The comparative study of the different extractive techniques of naringin was made, using grapefruit peel (Citrus paradisi). The best conditions for previous preparation of the material are the fragmentation of fresh peel and drying through a drying chamber and subsequent fragmentation. For fresh peel it turns to be more convenient the extraction with ethyl alcohol by Soxhlet system (obtaining 26 g/kg of fresh weight), while for dried peel the best results are obtained in the extraction with the mixture ethyl alcohol - water in the proportions 70:30 by maceration (20 g/kg of fresh weight) and reflux (22 g/kg of fresh weight). Evidences of the importance of water in the extraction process were observed. The values of naringin concentration in peel of different varieties of Citrus paradisi of the region of Argentinean North West were determined. Fil: Giannuzzo, Amelia N.. Universidad Nacional de Santiago del Estero. Facultad de Agronomía y Agroindustrias. Instituto de Ciencias Químicas; Argentina Fil: Nazareno, Mónica Azucena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Santiago del Estero. Universidad Nacional de Santiago del Estero. Centro de Investigaciones y Transferencia de Santiago del Estero; Argentina. Universidad Nacional de Santiago del Estero. Facultad de Agronomía y Agroindustrias. Instituto de Ciencias Químicas; Argentina Fil: Mishima, Horacio Tacashi. Universidad Nacional de Santiago del Estero. Facultad de Agronomía y Agroindustrias. Instituto de Ciencias Químicas; Argentina Fil: Lopez, Beatriz Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Santiago del Estero. Universidad Nacional de Santiago del Estero. Centro de Investigaciones y Transferencia de Santiago del Estero; Argentina. Universidad Nacional de Santiago del Estero. Facultad de Agronomía y Agroindustrias. Instituto de Ciencias Químicas; Argentina

Submitted by Ricardo Cedraz Duque Moliterno (ricardo.moliterno@uefs.br) on 2020-05-06T23:06:42Z No. of bitstreams: 1 Disserta??o VMAlmeida.pdf: 1634956 bytes, checksum: 9f5b38cba5ae57a6d0ac93a89d3abcc0 (MD5) Made available in DSpace on 2020-05-06T23:06:42Z (GMT). No. of bitstreams: 1 Disserta??o VMAlmeida.pdf: 1634956 bytes, checksum: 9f5b38cba5ae57a6d0ac93a89d3abcc0 (MD5) Previous issue date: 2011-03-25 Funda??o de Amparo ? Pesquisa do Estado da Bahia - FAPEB Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq Flavonoid glycosides are very important compounds among natural products. They show several biological activities, mainly scavenger. They are characterized by a low solubility and stability in lipophilic media. So its use has been difficult in pharmaceutic, cosmetic and food preparation. In order to take advantage of these properties, the enzymatic acylation of these molecules employing fatty acids and immobilized lipase B from Candida antarctica has been suggested as a interesting route because don?t affect the biological activities. The aim of this work was to compare the performance of the esterification and transesterification reactions during the enzymatic acylation of naringin with ricinoleic acid and castor oil, respectively. The ricinoleic acid (12-hydroxy-9-Z-octadecenoic acid) is an hidroxy-unsaturated fatty acid that naturally occurs in castor oil. The enzymatic synthesis of flavonoid ester was carried out in shaker heating at 50?C under agitation during 120 hours using dry acetone. The reactions were monitored quantitatively by HPLC-DAD. The naringin ester was purified by liquid?liquid extraction followed by column chromatography. The obtained results indicated that the transesterification reactions obtained higher conversion yields (33%) compared to esterification (24%). These reactions also carried out so compare heating source differents such as conventional and with microwave energy. All data were statistically analyzed by ANAVA and Tukey?s test with 5% level of significance. The NMR analyses show the esterification which takes place on the primary OH of glucose moiety of naringin in C-6? position. The feasibility of the enzymatic acylation of naringin with an hydroxyl-unsaturated fatty acid from castor oil was clearly demonstrated in this work. Flavonoides glicosilados s?o compostos importantes entre os produtos naturais. Possuem atividade biol?gica variada, principalmente antioxidante, entretanto apresentam baixa solubilidade e estabilidade em meio lipof?lico, dificultando seu uso nas ind?stria farmac?utica, de cosm?ticos e de alimentos. Afim de melhorar essas propriedades, a acila??o enzim?tica flavonoides glicosideos com ?cidos graxos utilizando lipase B imobilizada de Candida antarctica tem sido sugerida como um caminho interessante, por n?o alterar sua atividade biol?gica. O objetivo deste trabalho foi comparar o desempenho das rea??es de esterifica??o e transesterifica??o atrav?s da acila??o enzim?tica de naringina com ?cido ricinoleico e ?leo de mamona, respectivamente. O ?cido ricinoleico (?cido 12-hidr?xi-9-Z-octadecen?ico) ? um ?cido graxo hidroxi-insaturado encontrado no ?leo de mamona. A s?ntese enzim?tica do ?ster da naringina foi realizada em incubadora de aquecimento sob agita??o a 50 ?C durante 120 horas em acetona previamente seca. As rea??es foram monitoradas quantitativamente por CLAE-DAD. O ?ster produzido foi purificado por extra??o l?quido-l?quido, seguido por cromatografia em coluna. Os resultados obtidos indicaram que a rea??o de transesterifica??o obteve maior rendimento de convers?o (33%) em rela??o ? esterifica??o (24%). Estas rea??es tamb?m foram realizadas para comparar o aquecimento convencional e atrav?s da energia de micro-ondas. Todos os dados foram analisados estatisticamente por ANOVA e pelo teste de Tukey a 5% de signific?ncia. As an?lises por RMN mostraram que a naringina foi esterificada na OH prim?ria da posi??o C-6?. A viabilidade da acila??o enzim?tica de naringina com ?cido graxo hidr?xi-insaturado do ?leo de mamona foi claramente demonstrada neste trabalho.

Flavonóides são pigmentos fenólicos de plantas que possuem várias atividades biológicas, sendo que muitas destas estão associados com prevenção de doenças crônicas como câncer e hiperlipidemia. Este trabalho teve como objetivo avaliar o efeito dos flavonóides naringina e rutina sobre o metabolismo lipídico de aves hipercolesterolêmicas. De acordo com os resultados pode-se observar que naringina e rutina reduziram significativamente as concentrações de colesterol total, colesterol-LDL, colesterol-VLDL e triacilgliceróis totais, não apresentando, entretanto, reduções nos níveis de colesterol-HDL. Hypocholesterolemic effect of flavonoids naringin and rutin. Flavonoids are pigments fenolics of plants that possess several biological activities, and many of these are associated with prevention of chronic diseases as cancer and hyperlipidemy. This work had as objective evaluates the effect of the flavonoids naringin and rutin on the metabolism lipidic of chicks hypercholesterolemic. In agreement with the results it can be observed that naringin and rutin reduced the levels of total cholesterol significantly, cholesterol-LDL, cholesterol-VLDL and triglycerols, not presenting, however, reductions in the levels of cholesterol-HDL.

Conselho Nacional de Desenvolvimento Científico e Tecnológico Vários estudos têm mostrado que os flavonóides e corantes naturais apresentam propriedades biológicas como antioxidante, antiinflamatória, hipolipidêmica, anticancerígena, antibacteriana e hipotensora. Além disso, o uso de corantes naturais em alimentos constitui atualmente uma tendência mundial, em função da maior demanda por produtos naturais. Objetivando avaliar o efeito hipolipidêmico dos flavonóides naringina e rutina, e dos corantes naturais cúrcuma e norbixina, isoladamente, e avaliar o efeito de colesterol, ácido cólico e diferentes concentrações de gordura suína na indução de hiperlipidemia em aves da linhagem Avian farms, foram realizados três ensaios. O primeiro e segundo ensaios foram realizados com pintos de corte, machos, de um dia de idade, normolipidêmicos, sendo que no primeiro ensaio os flavonóides e corantes naturais foram administradas via oral, misturados à ração, na dose de 20 mg por ave por dia. O segundo ensaio foi realizado para induzir a hiperlipidemia, com a administração, via oral, misturados à ração, das seguintes substâncias: 1% de colesterol e 0,1% de ácido cólico, 5% de gordura suína e 10% de gordura suína. No terceiro ensaio, os flavonóides e corantes naturais foram administrados via oral, misturados à ração, na dose de 20mg por ave por dia, sendo que este ensaio foi realizado com pintos machos, com hiperlipidemia induzida com 0,7% de colesterol, 0,1% de ácido cólico e 10% de gordura suína. Foram determinados os níveis plasmáticos de colesterol total, colesterol-HDL, colesterol-LDL, colesterol-VLDL e triacilgliceróis em todos os ensaios. No primeiro ensaio, os flavonóides e corantes naturais administrados em pintos de corte normais, não apresentaram efeito hipolipidêmico. No ensaio de indução de hiperlipidemia observou-se que os animais que receberam ração suplementada com 10% de gordura suína e os que receberam 0,7% de colesterol e 0,1% de ácido cólico apresentaram aumentos significativos nos níveis de todos os constituintes avaliados, constatando-se que estas substâncias, nas concentrações testadas, são efetivas na indução de hiperlipidemia. No terceiro ensaio, observou-se que todas as substâncias testadas (naringina, rutina, cúrcuma e norbixina) apresentaram reduções significativas nos níveis de colesterol total, colesterol- LDL, colesterol-VLDL e triacilgliceróis, não alterando os níveis de colesterol- HDL. Estes resultados demonstram que estas substâncias apresentam efeito hipolipidêmico quando administradas em aves com hiperlipidemia induzida pela dieta. Several studies have been showed that flavonoids and natural colorants present biological properties as antioxidant, antiinflammatory, hypolipidemic, anticarcinogenic, antibactericidal, antihypertensive. Natural colorants are important in foods and constitutes a world tendency due the largest demand for natural products. In order to evaluate the hypolipidaemic effect of flavonoids naringin, rutin and the natural colorants curcumin and norbixin, isolately, besides the cholesterol, colic acid and different concentrations of pig fat effects in the hyperlipidaemia induction in chicks of the lineage Avian farms, three experiments were accomplished. The first and second experiments were accomplished in male chicks, day one old, normolipidaemic, beeing the first by using flavonoids and natural colorants were administered orally, mixed to the ration, in the dosis of 20 mg/chick/day. The second experiment was accomplished by inducing the hyperlipidaemia, with the orally administration, mixed in the ration, of the following substances: 1% of cholesterol and 0,1% of colic acid and pig fat 5% and 10% concentration. In the third experiment, the flavonoids and natural colorants were orally administered, mixed to the ration, in the dosis of 20 mg/chick/day, and this experiment was accomplished in male chicks, with hyperlipidaemia induced by using 0,7% of cholesterol, 0,1% of colic acid and 10% of pig fat. The serum levels of total cholesterol, cholesterol-HDL, cholesterol-LDL, cholesterol-VLDL and triacilglycerols were dosed. The results showed that in the first experiment, was not observed hypolipidaemic effect. In the second experiment could be observed that the animals which received ration with 10% of pig fat and the others which received 0,7% of cholesterol and 0,1% of colic acid presented significant increases in all parameters evaluated, showing that these substances, were effective in hyperlipidaemia induction. In the third experiment, the results showed that naringin, rutin, curcumin and norbixin presented significant reductions in the total cholesterol, cholesterol-LDL, cholesterol-VLDL and triacilglycerols levels without increasing of cholesterol-HDL level. These results demonstrate that these substances present effect hypolipidaemic when administered in chicks with hyperlipidaemia induced by diet.