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1.
ACS Omega ; 5(41): 26374-26381, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33110965

RESUMO

Immunostimulatory activity comprises specific and nonspecific immune responses stimulated by internal and external factors. Arabinoxylan is well known for its immunostimulatory activity in vivo and in vitro, although the biological activities of arabinoxylan oligosaccharides depend on their structural features. In this study, we aimed to evaluate in vitro and in vivo the immunostimulatory activity of high-content active arabinoxylan (HCAA) obtained from rice bran through bioconversion by microorganisms and acid hydrolysis. Three microorganisms, Penicillium rocheforti, Aspergillus oryzae, and Pleurotus osteatus, and three different acid concentrations of hydrochloric acid (5, 10, and 20%) and acetic acid (25, 50, and 75%) were used for producing HCAA. HPLC analysis of arabinose and xylose content revealed that fermentation with P. rocheforti followed by hydrolysis with 5% hydrochloric acid was the most efficient to produce HCAA. GPC analysis of HCAA indicates that HCAA is a complex of various forms of saccharides and shows an average molecular weight of 625. Further, in vitro evaluation disclosed that exposure to HCAA (10-200 µg/mL) increased cell viability in mice splenic cells and RAW 264.7 cells. Additionally, exposure of mice to oral administration of HCAA (100 mg/kg) for 4-7 days increased lymphokine-activated killer (LAK)- and macrophage-mediated cytotoxic activity in cancer cells (YAC-1). Furthermore, in vitro exposure to HCAA and oral administrations in mice revealed increased interferon-γ (IFN-γ) and interleukin-10 (IL-10) protein expression through western blot analysis in RAW 264.7 cells and isolated splenic cells. Our results suggest that HCAA developed by bioconversion and acid hydrolysis may enhance immune responses in vivo and in vitro.

2.
Cienc. tecnol. salud ; 7(1)2020. ^c27 cmilus
Artigo em Espanhol | LILACS | ID: biblio-1121008

RESUMO

La prevalencia de enfermedad renal ha aumentado considerablemente en la última década y está previsto que crezca en los próximos años. Recientemente, diversos modelos se han utilizado para entender los procesos fisiopatológicos de daño renal y para la búsqueda de futuros candidatos farmacológicos. El objetivo de esta revisión es proporcionar una descripción de la evidencia actual de modelos in vitro e in vivo de nefrotoxicidad, nefropatía diabética y deshidratación, y los fundamentos de las principales vías de señalización fisiopatológicas, con el fin de proponer biomarcadores candidatos para futura investigación farmacológica. Actualmente, los roedores constituyen un pilar importante en estudios de daño renal, existiendo diferencias específicas según el estímulo nocivo, lo que sugiere considerar para un modelo relevante aspectos como especie, cepa, género y estructuras renales objetivo. Diversas estructuras renales se han complementado in vitro, principalmente a partir de líneas celulares, como del epitelio tubular, podocitos, células mesangiales glomerulares y conducto colector medular interno. Este enfoque se ha utilizado como complementario en modelos de nefrotoxicidad por exposición a aminoglucósidos (principalmente), deshidratación por cloruro de sodio hiperosmolar, y nefropatía diabética por medio de glucosa alta y productos derivados de glucólisis y glicación. Recientemente, estos modelos han mostrado similitud en diversas rutas de señalización celular, con algunos biomarcadores en común, entre múltiples causas de daño renal como el daño oxidativo, disfunción mitocondrial, procesos inflamatorios, desregulación de sistemas de defensa y sobrevivencia celular, y apoptosis. El enfoque en seleccionar biomarcadores relevantes contribuirá al diseño de estrategias terapéuticas de nefroprotectores sobre múltiples factores etiológicos.


The prevalence of kidney disease has increased considerably in the last decade and is expected to growth in the coming years. Recently, various models have been used to understand the pathophysiological processes of kidney damage and to search for future pharmacological candidates. The aim of this review is to provide a description of the current evidence of in vitro and in vivo models of nephrotoxicity, diabetic nephropathy and dehydration, and the foundations of the main pathophysiological signaling pathways, in order to propose candidate biomarkers for future drug discovery. Currently, rodents are an important pillar in studies of kidney damage, with specific differences depending on the noxious stimulus, which suggests considering aspects such as species, strain, gender and target structures for a relevant model. Several renal structures have been complemented through in vitro approaches, mainly using cell lines, such as the tubular epithelium, podocytes, glomerular mesangial cells and inner medullary collecting duct. These cells have been used as models of nephrotoxicity by exposure to aminoglycosides (mainly), dehydration by exposure to hyperosmolar sodium chloride, and diabetic nephropathy by exposure to high glucose and products derived from glycolysis and glycation. Recently, these models have shown common cell signaling pathways on multiple etiologies of kidney injury, sharing several biomarkers such as oxidative damage, mitochondrial dysfunction, inflammatory processes, dysregulation of defense systems and cell survival, and apoptosis. Approaching kidney injury based on the selection of relevant biomarkers will contribute to the design of therapeutic strategies for nephroprotection on multiple etiological factors.


Assuntos
Humanos , Animais , Masculino , Adolescente , Adulto , Ratos , Técnicas In Vitro/métodos , Biomarcadores , Nefropatias Diabéticas , Roedores , Ratos Wistar , Apoptose , Epitélio , Células Mesangiais , Glucose/análise
3.
Brain Res ; 1715: 235-244, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30958992

RESUMO

Early-response auditory evoked potentials (AEPs) in humans are significantly altered in tinnitus. These changes are closely related to that seen in animals, leading to new approaches to study tinnitus based on objective parameters. The purpose of this study was to characterize the AEPs in animals with tinnitus, by assessing early to late latency responses. For behavioral evaluation, rats were trained using positive reinforcement to press a lever in the presence of an auditory stimulus and to not press during silence. The auditory brainstem response (ABR), middle latency response (MLR) and auditory late latency response (LLR) were correlated to the false-positive responses (pressing the lever during silence), after oral administrations of Sodium Salicylate (SS, 350 mg/kg). In the present study, SS significantly increased the hearing thresholds and reduced ABR peak I amplitudes across the frequency range (4-32 kHz). In contrast, increased amplitudes were observed for several peaks in ABR, MLR, and LLR. Moreover, reduced ABR latencies in response to 8, 16 and 24 kHz tone bursts were observed after SS administration. Similarly, the central evaluation also revealed significantly reduced latencies in MLR and LLR during SS administration. In contrast, increased latencies were observed for ABR latencies in response to 32 kHz tone bursts, and at the P1-N1 component of LLR. Correlational analysis revealed that latencies and amplitudes of peaks II and IV (8 and 16 kHz) of ABR, and N2 latency and P2-N2 amplitude of LLR were associated with behavioral tinnitus. We suggest that AEPs can be used in the rat to evaluate the reduced sensory input and the increased central gain in SS-induced tinnitus, as well as reduced latencies (8-16 kHz) to distinguish between hearing loss and tinnitus.


Assuntos
Potenciais Evocados Auditivos/fisiologia , Audição/fisiologia , Zumbido/fisiopatologia , Estimulação Acústica/métodos , Animais , Percepção Auditiva/fisiologia , Limiar Auditivo/fisiologia , Tronco Encefálico/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Feminino , Perda Auditiva , Ruído , Ratos , Ratos Sprague-Dawley , Tempo de Reação/fisiologia , Salicilatos/farmacologia
4.
J Ginseng Res ; 43(2): 272-281, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30976165

RESUMO

Background: Diabetic sensorineural damage is a complication of the sensory neural system, resulting from long-term hyperglycemia. Red ginseng (RG) has shown efficacy for treatment of various diseases, including diabetes mellitus; however, there is little research about its benefit for treating sensorineural damage. Therefore, we aim to evaluate RG efficacy in alloxan-induced diabetic neuromast (AIDN) zebrafish. Methods: In this study, we developed and validated an AIDN zebrafish model. To assess RG effectiveness, we observed morphological changes in live neuromast zebrafish. Also, zebrafish has been observed to have an ultrastructure of hair-cell cilia under scanning electron microscopy. Thus, we recorded these physiological traits to assess hair cell function. Finally, we confirmed that RG promoted neuromast recovery via nerve growth factor signaling pathway markers. Results: First, we established an AIDN zebrafish model. Using this model, we showed via live neuromast imaging that RG fostered recovery of sensorineural damage. Damaged hair cell cilia were recovered in AIDN zebrafish. Furthermore, RG rescued damaged hair cell function through cell membrane ion balance. Conclusion: Our data suggest that RG potentially facilitates recovery in AIDN zebrafish, and its mechanism seems to be promotion of the nerve growth factor pathway through increased expression of topomyosin receptor kinase A, transient receptor potential channel vanilloid subfamily type 1, and mitogen-activated protein kinase phosphorylation.

5.
Nutrients ; 11(1)2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30626089

RESUMO

Sensorineural hearing loss (SNHL) is one of the most common causes of disability, affecting over 466 million people worldwide. However, prevention or therapy of SNHL has not been widely studied. Avocado oil has shown many health benefits but it has not yet been studied in regards to SNHL. Therefore, we aimed to investigate the efficacy of avocado oil on SNHL in vitro and in vivo and elucidate its mode of action. For the present study, we used enhanced functional avocado oil extract (DKB122). DKB122 led to recovery of otic hair cells in zebrafish after neomycin-induced otic cell damage. Also, DKB122 improved auditory sensory transmission function in a mouse model of noise induced-hearing loss and protected sensory hair cells in the cochlea. In addition, RNA sequencing was performed to elucidate the mechanism involved. KEGG pathway enrichment analysis of differentially expressed genes showed that DKB122 protected House Ear Institute-Organ of Corti 1 (HEI-OC1) cells against neomycin-related alterations in gene expression due to oxidative stress, cytokine production and protein synthesis.


Assuntos
Aminoácidos/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Células Ciliadas Auditivas/efeitos dos fármacos , Perda Auditiva Neurossensorial , Persea/química , Fitoterapia , Óleos Vegetais/farmacologia , Animais , Percepção Auditiva/efeitos dos fármacos , Cóclea/citologia , Cóclea/efeitos dos fármacos , Cóclea/metabolismo , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/fisiologia , Perda Auditiva Provocada por Ruído/tratamento farmacológico , Perda Auditiva Provocada por Ruído/genética , Perda Auditiva Provocada por Ruído/metabolismo , Perda Auditiva Provocada por Ruído/fisiopatologia , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/metabolismo , Perda Auditiva Neurossensorial/fisiopatologia , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Óleos Vegetais/uso terapêutico , Análise de Sequência de RNA , Peixe-Zebra
6.
J Ethnopharmacol ; 231: 409-428, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30439402

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In Traditional Oriental Medicine (TOM), the development of hearing pathologies is related to an inadequate nourishment of the ears by the kidney and other organs involved in regulation of bodily fluids and nutrients. Several herbal species have historically been prescribed for promoting the production of bodily fluids or as antiaging agents to treat deficiencies in hearing. AIM OF REVIEW: The prevalence of hearing loss has been increasing in the last decade and is projected to grow considerably in the coming years. Recently, several herbal-derived products prescribed in TOM have demonstrated a therapeutic potential for acquired sensorineural hearing loss and tinnitus. Therefore, the aims of this review are to provide a comprehensive overview of the current known efficacy of the herbs used in TOM for preventing different forms of acquired sensorineural hearing loss and tinnitus, and associate the traditional principle with the demonstrated pharmacological mechanisms to establish a solid foundation for directing future research. METHODS: The present review collected the literature related to herbs used in TOM or related compounds on hearing from Chinese, Korean, and Japanese herbal classics; library catalogs; and scientific databases (PubMed, Scopus, Google Scholar; and Science Direct). RESULTS: This review shows that approximately 25 herbal species and 40 active compounds prescribed in TOM for hearing loss and tinnitus have shown in vitro or in vivo beneficial effects for acquired sensorineural hearing loss produced by noise, aging, ototoxic drugs or diabetes. The inner ear is highly vulnerable to ischemia and oxidative damage, where several TOM agents have revealed a direct effect on the auditory system by normalizing the blood supply to the cochlea and increasing the antioxidant defense in sensory hair cells. These strategies have shown a positive impact on maintaining the inner ear potential, sustaining the production of endolymph, reducing the accumulation of toxic and inflammatory substances, preventing sensory cell death and preserving sensory transmission. There are still several herbal species with demonstrated therapeutic efficacy whose mechanisms have not been deeply studied and others that have been traditionally used in hearing loss but have not been tested experimentally. In clinical studies, Ginkgo biloba, Panax ginseng, and Astragalus propinquus have demonstrated to improve hearing thresholds in patients with sensorineural hearing loss and alleviated the symptoms of tinnitus. However, some of these clinical studies have been limited by small sample sizes, lack of an adequate control group or contradictory results. CONCLUSIONS: Current therapeutic strategies have proven that the goal of the traditional oriental medicine principle of increasing bodily fluids is a relevant approach for reducing the development of hearing loss by improving microcirculation in the blood-labyrinth barrier and increasing cochlear blood flow. The potential benefits of TOM agents expand to a multi-target approach on different auditory structures of the inner ear related to increased cochlear blood flow, antioxidant, anti-inflammatory, anti-apoptotic and neuroprotective activities. However, more research is required, given the evidence is very limited in terms of the mechanism of action at the preclinical in vivo level and the scarce number of clinical studies published.


Assuntos
Perda Auditiva Neurossensorial/tratamento farmacológico , Medicina Tradicional do Leste Asiático , Animais , Descoberta de Drogas , Etnofarmacologia , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/metabolismo , Perda Auditiva Neurossensorial/fisiopatologia , Humanos
7.
Food Sci Biotechnol ; 27(4): 1023-1030, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30263831

RESUMO

A preliminary study revealed that a 10 µg/mL n-BuOH fraction of Malva verticillata aerial parts significantly enhanced splenocyte proliferation and induced significant enhancement of natural-killer (NK) cell activity against tumor cells (YAC-1). This study was initiated to identify the principal components that exhibited these activities, and four glycerides were isolated through repeated SiO2 and ODS column chromatography. Structures of compounds 1-4 were determined to be (2S)-1-O-palmitoyl glyceride, (2S)-1-O-stearoyl glyceride, (2S)-1-O-linolenoyl glyceride, and (2S)-1,2-di-O-linoleoyl glyceride, respectively. Compounds 1-3 showed potential immune-enhancing activity in murine splenocyte and natural-killer (NK) cells at 10 µM. In contrast, compound 4 showed weak activity, indicating the monoacyl glycerides (1-3) are more effective than diacyl glyceride (4). Also, the longer the carbon number of the fatty acid in monoacyl glyceride, the better the activity, and the monoacyl glyceride including an unsaturated fatty acid (3) is more effective than the glycerides including the saturated fatty acids (1-2).

8.
Sci Rep ; 8(1): 3072, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29449678

RESUMO

The cerebellum plays a key role in motor tasks, but its involvement in cognition is still being considered. Although there is an association of different psychiatric and cognitive disorders with cerebellar impairments, the lack of time-course studies has hindered the understanding of the involvement of cerebellum in cognitive and non-motor functions. Such association was here studied using the Purkinje Cell Degeneration mutant mouse, a model of selective and progressive cerebellar degeneration that lacks the cytosolic carboxypeptidase 1 (CCP1). The effects of the absence of this enzyme on the cerebellum of mutant mice were analyzed both in vitro and in vivo. These analyses were carried out longitudinally (throughout both the pre-neurodegenerative and neurodegenerative stages) and different motor and non-motor tests were performed. We demonstrate that the lack of CCP1 affects microtubule dynamics and flexibility, defects that contribute to the morphological alterations of the Purkinje cells (PCs), and to progressive cerebellar breakdown. Moreover, this degeneration led not only to motor defects but also to gradual cognitive impairments, directly related to the progression of cellular damage. Our findings confirm the cerebellar implication in non-motor tasks, where the formation of the healthy, typical PCs structure is necessary for normal cognitive and affective behavior.


Assuntos
Proteínas de Ligação ao GTP/fisiologia , Microtúbulos/fisiologia , Células de Purkinje/metabolismo , D-Ala-D-Ala Carboxipeptidase Tipo Serina/fisiologia , Animais , Cerebelo/metabolismo , Cerebelo/fisiologia , Cognição/fisiologia , Transtornos Cognitivos/metabolismo , Citoesqueleto/metabolismo , Citoesqueleto/fisiologia , Feminino , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Estudos Longitudinais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microtúbulos/metabolismo , Transtornos Motores/genética , Células de Purkinje/fisiologia , D-Ala-D-Ala Carboxipeptidase Tipo Serina/genética , D-Ala-D-Ala Carboxipeptidase Tipo Serina/metabolismo
9.
Phytomedicine ; 36: 128-136, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29157806

RESUMO

BACKGROUND: Protection of cochlear function and reconstruction of neuronal networks in damaged auditory sensory structures is crucial for therapeutic treatment of diabetic hearing loss. Nerve growth factor (NGF) has been used as a novel therapeutic target to protect against the neurodegenerative effects of Diabetes Mellitus (DM). PURPOSE: We aimed to evaluate the potential effect of trigonelline (TRG) on reducing auditory damage produced by DM using NGF as a potential marker. METHOD: Docking simulations were carried out using Autodock Vina software and visualized using Discovery Studio. Morphological analysis of hair cells and neuromasts was performed on alloxan-induced diabetic zebrafish by fluorescence and scanning electron microscopy. Blockage of NGF receptor phosphorylation with K-252a was used to evaluate TRG and NGF action. Further assessment of NGF by ELISA on a primary culture of spiral ganglion cells was performed as a marker of neuronal function on the hearing system. Finally, auditory function was assessed in LepR(db/db) mice using auditory brainstem response (ABR) and transient evoked otoacoustic emission (TEOAE) during 8 weeks. RESULTS: Docking simulations showed that TRG binds to the active site of NGF through molecular interactions with Lysine88 (Lys88) and Tyrosine52 (Tyr52). TRG treatment significantly reduced hair cell loss and neuromast damage in diabetic zebrafish (P < .05). Further evaluation revealed a significant increase in the number of neuromasts after NGF administration (P < .001). TRG and NGF action was suppressed during blockage of NGF receptor phosphorylation. Moreover, spiral ganglion cells revealed significant elevation on NGF values after TRG treatment (P < .05). In vivo evaluation of LepR(db/db) mice revealed a significant reduction in the auditory damage produced under diabetic progression, characterized by reduced ABR hearing threshold shifts and increased signal-to-noise ratio in TEOAE (P < .05). CONCLUSIONS: This study suggests that the enhanced hearing function produced by TRG may be mediated by NGF, providing a potential therapeutic strategy for diabetic hearing loss.


Assuntos
Alcaloides/farmacologia , Limiar Auditivo/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Células Ciliadas Auditivas/efeitos dos fármacos , Fator de Crescimento Neural/metabolismo , Alcaloides/química , Animais , Carbazóis/farmacologia , Domínio Catalítico , Simulação por Computador , Diabetes Mellitus Experimental/fisiopatologia , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Alcaloides Indólicos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Fator de Crescimento Neural/química , Emissões Otoacústicas Espontâneas/efeitos dos fármacos , Ratos Sprague-Dawley , Peixe-Zebra
10.
J Ginseng Res ; 41(1): 103-112, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28123328

RESUMO

BACKGROUND: 20(S)-Protopanaxadiol 20-O-D-glucopyranoside, also called compound K (CK), exerts antidiabetic effects that are mediated by insulin secretion through adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in pancreatic ß-cells. However, the antidiabetic effects of CK may be limited because of its low bioavailability. METHODS: In this study, we aimed to enhance the antidiabetic activity and lower the toxicity of CK by including it with ß-cyclodextrin (CD) (CD-CK), and to determine whether the CD-CK compound enhanced pancreatic islet recovery, compared to CK alone, in an alloxan-induced diabetic zebrafish model. Furthermore, we confirmed the toxicity of CD-CK relative to CK alone by morphological changes, mitochondrial damage, and TdT-UTP nick end labeling (TUNEL) assays, and determined the ratio between the toxic and therapeutic dose for both compounds to verify the relative safety of CK and CD-CK. RESULTS: The CD-CK conjugate (EC50 = 2.158µM) enhanced the recovery of pancreatic islets, compared to CK alone (EC50 = 7.221µM), as assessed in alloxan-induced diabetic zebrafish larvae. In addition, CD-CK (LC50 = 20.68µM) was less toxic than CK alone (LC50 = 14.24µM). The therapeutic index of CK and CD-CK was 1.98 and 9.58, respectively. CONCLUSION: The CD-CK inclusion complex enhanced the recovery of damaged pancreatic islets in diabetic zebrafish. The CD-CK inclusion complex has potential as an effective antidiabetic efficacy with lower toxicity.

11.
Cienc. tecnol. salud ; 2(2): 141-147, jul.-dic. 2015. ilus
Artigo em Espanhol | LILACS | ID: biblio-834326

RESUMO

La elevación de los lípidos sanguíneos se ha convertido en un riesgo común de enfermedades cardiovasculares, en especial en el caso del colesterol y triglicéridos, también a problemas pancreáticos, de la córnea, bazo e hígado. Hibiscus sabdariffa L., es una especie medicinal de la familia Malvaceae, su efecto sobre la reducción de los lípidos séricos se ha mencionado en varios estudios. El objetivo del presente estudio consistió en evaluar la actividad de un extracto acuoso de los cálices de H. sabdariffa, para reducir los lípidos séricos en dos grupos de individuos, con valores de triglicéridos mayores de 150 mg/dL, al recibir una dosis de 15 mg de antocianinas totales al día, dividida entres veces, por un periodo de dos meses para establecer su influencia, dependiendo del momento de su administración, un grupo recibiéndola antes de la comida y otro durante la misma. El extracto de H. sabdariffa mostró un efecto hipotrigliceridémico significativo (p = 0.034), al finalizar el tratamiento, únicamente al administrar el extracto antes de las comidas. Al mismo tiempo, no se observó alteración en los niveles de colesterol total, colesterol contenido en las lipoproteínas de baja densidad y colesterol contenido en las proteínas de alta densidad en ninguno de los dos grupos evaluados. Los resultados sugieren que los extractos acuosos de H. sabdariffa podrían ser utilizados para ejercer una acción en los triglicéridos plasmáticos, dependiente del consumo de alimentos, y del momento de administración.


Elevated blood lipids, cholesterol and triglycerides, has become a common health risk worldwide, not only for cardiovascular diseases, especially in the case of cholesterol and triglycerides, but also in pancreatic, corneal, spleen and liver problems. Hibiscus sabdariffa L., is a medicinal plant of the Malvaceae family, its effect on reducing serum lipids is mentioned in several studies. The purpose of this study was to evaluate the activity of an aqueous extract of H. sabdariffa at a dose of 15 mg of anthocyanins daily, divided in three times a day, either before or during meals, over a period of 2 months, to decrease plasma triglycerides in subjects with values above 150 mg/dL, in order to establish the influence of the time of administration in this effect. The extract showed a hypotriglyceridemic effect (p = 0.034) in the first and second month of treatment, only when administered before meals. At the same time, no significant changes were observed in levels of total cholesterol, cLDL, cHDL in any of the evaluated groups. These results suggest that the aqueous extracts of H. sabdariffa could be used to reduce action in plasma triglycerides levels only when administered prior to meals.


Assuntos
Humanos , Masculino , Feminino , Antocianinas , Dislipidemias/sangue , Extratos Vegetais , Triglicerídeos
12.
Eur Neuropsychopharmacol ; 25(10): 1683-94, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26235957

RESUMO

Nicotine exerts its addictive influence through the meso-cortico-limbic reward system, where the striatum is essential. Nicotine addiction involves different neurotransmitters, nitric oxide (NO) being especially important, since it triggers the release of the others by positive feedback. In the nervous system, NO is mainly produced by nitric oxide synthase 1 (NOS1). However, other subtypes of synthases can also synthesize NO, and little is known about the specific role of each isoform in the process of addiction. In parallel, NOS activity and nicotine addiction are also affected by stress and sexual dimorphism. To determine the specific role of this enzyme, we analyzed both NOS expression and NO synthesis in the striatum of wild-type and NOS1-knocked out (KO) mice of both sexes in situations of nicotine sensitization and stress. Our results demonstrated differences between the caudate-putamen (CP) and nucleus accumbens (NA). With respect to NOS1 expression, the CP is a dimorphic region (27.5% lower cell density in males), but with a stable production of NO, exclusively due to this isoform. Thus, the nitrergic system of CP may not be involved in stress or nicotine addiction. Conversely, the NA is much more variable and strongly involved in both situations: its NO synthesis displays dimorphic variations at both basal (68.5% reduction in females) and stress levels (65.9% reduction in males), which disappear when nicotine is infused. Thus, the KO animals showed an increase in NO production (21.7%) in the NA, probably by NOS3, in an attempt to compensate the lack of NOS1.


Assuntos
Núcleo Caudado/enzimologia , Óxido Nítrico Sintase Tipo I/metabolismo , Núcleo Accumbens/enzimologia , Putamen/enzimologia , Estresse Psicológico/enzimologia , Tabagismo/enzimologia , Animais , Núcleo Caudado/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Isoenzimas/metabolismo , Masculino , Camundongos da Linhagem 129 , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo I/genética , Núcleo Accumbens/efeitos dos fármacos , Putamen/efeitos dos fármacos , Caracteres Sexuais
13.
Artigo em Inglês | MEDLINE | ID: mdl-25878713

RESUMO

Diabetes mellitus (DM) is a metabolic disease that involves disorders such as diabetic retinopathy, diabetic neuropathy, and diabetic hearing loss. Recently, neurotrophin has become a treatment target that has shown to be an attractive alternative in recovering auditory function altered by DM. The aim of this study was to evaluate the effect of DA9801, a mixture of Dioscorea nipponica and Dioscorea japonica extracts, in the auditory function damage produced in a STZ-induced diabetic model and to provide evidence of the mechanisms involved in enhancing these protective effects. We found a potential application of DA9801 on hearing impairment in the STZ-induced diabetic model, demonstrated by reducing the deterioration produced by DM in ABR threshold in response to clicks and normalizing wave I-IV latencies and Pa latencies in AMLR. We also show evidence that these effects might be elicited by inducing NGF related through Nr3c1 and Akt. Therefore, this result suggests that the neuroprotective effects of DA9801 on the auditory damage produced by DM may be affected by NGF increase resulting from Nr3c1 via Akt transformation.

14.
Neuroscientist ; 21(6): 637-52, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25171812

RESUMO

Bone marrow stem cells are the best known stem cell type and have been employed for more than 50 years, especially in pathologies of the hematopoietic and immune systems. However, their therapeutic potential is much broader, and they can also be employed to palliate neural diseases. Apart from their plastic properties, these cells lack the legal or ethical constraints of other stem cell populations, that is, embryonic stem cells. Current research addressing the integration of bone marrow-derived cells into the neural circuits of the central nervous system, their features, and applications is a hotspot in neurobiology. Nevertheless, as in other leading research lines the efficacy and possibilities of their application depend on technical procedures, which are still far from being standardized. Accordingly, for efficient research this large range of variants should be taken into account as they could lead to unexpected results. Rather than focusing on clinical aspects, this review offers a compendium of the methodologies aimed at providing a guide for researchers who are working in the field of bone marrow transplantation in the central nervous system. It seeks to be useful for both introductory and trouble-shooting purposes, and in particular for dealing with the large array of bone marrow transplantation protocols available.


Assuntos
Transplante de Medula Óssea/métodos , Doenças do Sistema Nervoso/terapia , Transplante de Células-Tronco/métodos , Animais , Humanos
15.
Psychopharmacology (Berl) ; 231(4): 695-706, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24081550

RESUMO

RATIONALE: Nitric oxide (NO) is a messenger synthesized in both the neuronal and glial populations by nitric oxide synthase type 1 (NOS1). Nicotine regulates NO production in a sex-dependent manner, both molecules being involved in motor function. OBJECTIVE: The present study evaluates sex differences in motor coordination, general movement, and anxiety-related responses resulting from both constant and continuous nicotine treatment and the genetic depletion of NOS1 activity. METHODS: Male and female mice were analyzed with the open-field and the rotarod tests. To understand the role of NO, knockout mice for NOS1 (NOS1-/-) were analyzed. Nicotine was administered continuously at a dose of 24 mg/kg/day via osmotic mini-pumps over 14 days because the behavioral effects elicited are similar to those observed with discontinuous administration. RESULTS: Data analyses revealed noteworthy sex differences derived from NOS1 depletion. Control NOS1-/- males exhibited an exacerbated anxiety-related response in relation to control NOS1-/- females and control wild-type (WT) males; these differences disappeared in the nicotine-administered NOS1-/- males. Additionally, nicotine administration differentially affected the horizontal movements of NOS1-/- females with respect to WT animals. NO depletion affected male but not female motor coordination improvement along the test days. However, the drug affected female motor coordination only at the end of the administration period. CONCLUSIONS: We show for the first time that NO affects motor and anxiety behaviors in a sex-dependent manner. Moreover, the behavioral effects of constant nicotine administration are dimorphic and dependent on NO production.


Assuntos
Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Atividade Motora/fisiologia , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Óxido Nítrico Sintase Tipo I/metabolismo , Animais , Defecação/efeitos dos fármacos , Defecação/fisiologia , Feminino , Asseio Animal/efeitos dos fármacos , Asseio Animal/fisiologia , Masculino , Camundongos , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo I/genética , Prática Psicológica , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Fatores Sexuais , Fatores de Tempo
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