RESUMO
Consumption of white rice (WR) has been shown to predispose individuals to metabolic disorders. However, brown rice (BR), which is relatively richer in bioactive compounds, possesses anti-glycaemic and antioxidant effects. In this study, fifteen cultivars of paddy rice that are predominantly consumed in North West Nigeria were analysed for their nutritional composition, bioactive contents and effects on metabolic outcomes in a fruit fly model. Gene expression analyses were conducted on the whole fly, targeting dPEPCK, dIRS, and dACC. The protein, carbohydrate, and fibre contents and bioactives of all BR cultivars were significantly different (p < 0.05) from the WR cultivars. Moreover, it was demonstrated that the glucose and trehalose levels were significantly higher (p < 0.05), while glycogen was significantly lower (p < 0.05) in the WR groups compared to the BR groups. Similarly, the expression of dACC and dPEPCK was upregulated, while that of dIRS was downregulated in the WR groups compared to the BR groups. Sex differences (p < 0.05) were observed in the WR groups in relation to the nutrigenomic effects. Our findings confirm metabolic perturbations in fruit flies following consumption of WR via distortion of insulin signalling and activation of glycogenolysis and gluconeogenesis. BR prevented these metabolic changes possibly due to its richer nutritional composition.
Assuntos
Doenças Metabólicas , Oryza , Glicemia/metabolismo , Insulina/metabolismo , Nutrigenômica , Oryza/química , Drosophila , AnimaisRESUMO
The oxidative stress resulting from the production of reactive oxygen species plays a vital role in inflammatory processes and is associated with neurodegenerative changes. In view of the ability of germinated brown rice (GBR) to improve learning and memory, this present study aimed to investigate the mechanistic basis of GBR's neuroprotection in a high-fat diet (HFD)-induced oxidative changes in adult Sprague-Dawley rats. Ferulate-rich GBR ethyl acetate extract (GBR-EA; 100 mg/kg and 200 mg/kg body weight) was supplemented orally for the last 3 months of 6 months HFD feeding during the study. GBR-EA supplementation was found to improve lipid profile and serum antioxidant status, when compared to the HFD group. Elevated mRNA expressions of SOD1, SOD2, SOD3, Catalase, and GPX were demonstrated in the frontal cortex and hippocampus of GBR-EA treated animals. The pro-inflammatory changes induced by HFD in the hippocampus were attenuated by GBR-EA through the downregulation of CRP and TNF- α and upregulation of PPAR-γ. GBR also reduced the hippocampal mRNA expression and enzyme level of acetylcholinesterase. In conclusion, this study proposed the possible transcriptomic regulation of antioxidant and inflammation in neurodegenerative processes resulting from high cholesterol consumption, with an emphasis on GBR's potential to ameliorate such changes.
Assuntos
Dieta Hiperlipídica , Oryza , Acetatos , Acetilcolinesterase , Animais , Antioxidantes/farmacologia , Encéfalo , Dieta Hiperlipídica/efeitos adversos , Estresse Oxidativo , RNA Mensageiro , Ratos , Ratos Sprague-DawleyRESUMO
In this study, anti-proliferative effects of C. calcitrans extract and its fucoxanthin rich fraction (FxRF) were assessed on human liver HepG2 cancer cell line. Efficacy from each extract was determined by cytotoxicity assay, morphological observation, and cell cycle analysis. Mechanisms of action observed were evaluated using multiplex gene expression analysis. Results showed that CME and FxRF induced cytotoxicity to HepG2 cells in a dose and time-dependent manner. FxRF (IC50: 18.89 µg.mL-1) was found to be significantly more potent than CME (IC50: 87.5 µg.mL-1) (p < 0.05). Gene expression studies revealed that anti-proliferative effects in treated cells by C. calcitrans extracts were mediated partly through the modulation of numerous genes involved in cell signaling (AKT1, ERK1/2, JNK), apoptosis (BAX, BID, Bcl-2, APAF, CYCS) and oxidative stress (SOD1, SOD2, CAT). Overall, C. calcitrans extracts demonstrated effective intervention against HepG2 cancer cells where enhanced apoptotic activities were observed with increased fucoxanthin content.
RESUMO
Adipose tissue is one of the major organs responsible for rapid restoration of postprandial glucose fluxes. Being the major isoform of glucose transporter in adipose tissue, regulations of insulin-dependent GLUT4 trafficking have always been of research interest. The present study aimed to examine the molecular mechanisms underlying the efficacy of curculigoside and polyphenol-rich ethyl acetate fraction (EAF) of Molineria latifolia rhizome in triggering glucose uptake. We assessed the adipogenic potential and glucose uptake stimulatory activity of curculigoside and EAF by employing a murine 3T3-L1 adipocyte model. The transcriptional and translational expressions of selected intermediates in the insulin signalling pathway were evaluated. While curculigoside neither promoted adipogenesis nor activated peroxisome proliferator activated receptor gamma, treatment with polyphenol-rich EAF resulted otherwise. However, both treatments enhanced insulin-stimulated uptake of glucose. This was coupled with increased availability of GLUT4 at the plasma membrane of the differentiated adipocytes although the total GLUT4 protein level was unaffected. In addition, the treatment increased the phosphorylation of both AKT and mTOR, which have been reported to be associated with GLUT4 translocation. The present findings proposed that curculigoside and EAF increased glucose transport activity of 3T3-L1 adipocytes via GLUT4 translocation as a result of potential mTOR/AKT activation. The more potent efficacy observed with EAF suggested potential synergistic and multi-targeted action.
Assuntos
Adipócitos/efeitos dos fármacos , Benzoatos/farmacologia , Transportador de Glucose Tipo 4/metabolismo , Glucosídeos/farmacologia , Hypoxidaceae/química , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Adipócitos/metabolismo , Animais , Glucose/metabolismo , Transportador de Glucose Tipo 4/genética , Camundongos , Células NIH 3T3 , Transporte Proteico/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Rizoma/química , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genéticaRESUMO
Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-ß (Aß) accumulation due to abnormal amyloid-ß precursor protein (APP) processing and Aß metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Aß metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis. Despite the neuropharmacological attributes of black cumin seed (Nigella sativa) extracts and its main active compound, thymoquinone (TQ), limited records are available in relation to AD research. Nanoemulsion (NE) is exploited as drug delivery systems due to their capacity of solubilising non-polar active compounds and is widely examined for brain targeting. Herewith, the effects of thymoquinone-rich fraction nanoemulsion (TQRFNE), thymoquinone nanoemulsion (TQNE) and their counterparts' conventional emulsion in response to high fat/cholesterol diet (HFCD)-induced rats were investigated. Particularly, the Aß generation; APP processing, ß-secretase 1 (BACE1), γ-secretases of presenilin 1 (PSEN1) and presenilin 2 (PSEN2), Aß degradation; insulin degrading enzyme (IDE), Aß transportation; low density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) were measured in brain tissues. TQRFNE reduced the brain Aß fragment length 1-40 and 1-42 (Aß40 and Aß42) levels, which would attenuate the AD pathogenesis. This reduction could be due to the modulation of ß- and γ-secretase enzyme activity, and the Aß degradation and transportation in/out of the brain. The findings show the mechanistic actions of TQRFNE in response to high fat and high cholesterol diet associated to Aß generation, degradation and transportation in the rat's brain tissue.
Assuntos
Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Benzoquinonas/farmacologia , Insulisina/metabolismo , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Nanopartículas/química , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Regulação para Cima , Animais , Dieta Hiperlipídica , Regulação para Baixo/efeitos dos fármacos , Emulsões/química , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Presenilina-2/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacosRESUMO
The study determined the effect of thymoquinone rich fraction (TQRF) and thymoquinone (TQ) in the forms of nano- and conventional emulsions on learning and memory, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble ß-amyloid (Aß) levels in rats fed with a high fat-cholesterol diet (HFCD). The TQRF was extracted from Nigella sativa seeds using a supercritical fluid extraction system and prepared into nanoemulsion, which later named as TQRF nanoemulsion (TQRFNE). Meanwhile, TQ was acquired commercially and prepared into thymoquinone nanoemulsion (TQNE). The TQRF and TQ conventional emulsions (CE), named as TQRFCE and TQCE, respectively were studied for comparison. Statin (simvastatin) and non-statin (probucol) cholesterol-lowering agents, and a mild-to-severe Alzheimer's disease drug (donepezil) were served as control drugs. The Sprague Dawley rats were fed with HFCD for 6 months, and treated with the intervention groups via oral gavage daily for the last 3 months. As a result, HFCD-fed rats exhibited hypercholesterolaemia, accompanied by memory deficit, increment of lipid peroxidation and soluble Aß levels, decrement of total antioxidant status and down-regulation of antioxidants genes expression levels. TQRFNE demonstrated comparable effects to the other intervention groups and control drugs in serum biomarkers as well as in the learning and memory test. Somehow, TQRFNE was more prominent than those intervention groups and control drugs in brain biomarkers concomitant to gene and protein expression levels. Supplementation of TQRFNE into an HFCD thus could ameliorate memory deficit, lipid peroxidation and soluble Aß levels as well as improving the total antioxidant status and antioxidants genes expression levels.
Assuntos
Peptídeos beta-Amiloides/análise , Benzoquinonas/farmacologia , Emulsões/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Nanopartículas/química , Oxirredutases/genética , Fragmentos de Peptídeos/análise , Animais , Antioxidantes/metabolismo , Benzoquinonas/química , Benzoquinonas/uso terapêutico , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Encéfalo/metabolismo , Dieta Hiperlipídica , Emulsões/química , Regulação da Expressão Gênica/efeitos dos fármacos , Lipídeos/sangue , Masculino , Transtornos da Memória/tratamento farmacológico , Nigella sativa/química , Nigella sativa/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Nigella sativa Linn. (N. sativa) and its bioactive constituent Thymoquinone (TQ) have demonstrated numerous pharmacological attributes. In the present study, the neuroprotective properties of Thymoquinone-rich fraction (TQRF) and TQ against hydrogen peroxide- (H2O2-) induced neurotoxicity in differentiated human SH-SY5Y cells were investigated. TQRF was extracted using supercritical fluid extraction while TQ was acquired commercially, and their effects on H2O2 were evaluated using cell viability assay, reactive oxygen species (ROS) assay, morphological observation, and multiplex gene expression. Both TQRF and TQ protected the cells against H2O2 by preserving the mitochondrial metabolic enzymes, reducing intracellular ROS levels, preserving morphological architecture, and modulating the expression of genes related to antioxidants (SOD1, SOD2, and catalase) and signaling genes (p53, AKT1, ERK1/2, p38 MAPK, JNK, and NF-κß). In conclusion, the enhanced efficacy of TQRF over TQ was likely due to the synergism of multiple constituents in TQRF. The efficacy of TQRF was better than that of TQ alone when equal concentrations of TQ in TQRF were compared. In addition, TQRF also showed comparable effects to TQ when the same concentrations were tested. These findings provide further support for the use of TQRF as an alternative to combat oxidative stress insults in neurodegenerative diseases.
Assuntos
Antioxidantes/metabolismo , Apoptose , Benzoquinonas/química , Peróxido de Hidrogênio/química , Neurônios/metabolismo , Estresse Oxidativo , Laranja de Acridina/química , Linhagem Celular Tumoral , Sobrevivência Celular , Dieta , Regulação da Expressão Gênica , Humanos , Mitocôndrias/metabolismo , Nigella sativa/química , Extratos Vegetais/química , Propídio/química , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
Plant bioresources are relied upon as natural, inexpensive, and sustainable remedies for the management of several chronic diseases worldwide. Plants have historically been consumed for medicinal purposes based on traditional belief, but this trend is currently changing. The growing interest in the medicinal properties of plant bioresources stems from concerns of side effects and other adverse effects caused by synthetic drugs. This interest has yielded a better understanding of the roles of plant bioactive compounds in health promotion and disease prevention, including the underlying mechanisms involved in such functional effects. The desire to maximize the potential of phytochemicals has led to the development of "rich fractions," in which extracts contain bioactive compounds in addition to elevated levels of the primary compound. Although a rich fraction effectively increases the bioactivity of the extract, the standardization and quality assurance process can be challenging. However, the supercritical fluid extraction (SFE) system is a promising green technology in this regard. Future clinical and pharmacological studies are needed to fully elucidate the implications of these preparations in the management of human diseases, thereby fostering a move toward evidence-based medicine.
Assuntos
Benzoquinonas/farmacologia , Fenilpropionatos/farmacologia , Extratos Vegetais/farmacologia , Tocotrienóis/farmacologia , Animais , Humanos , FitoterapiaRESUMO
N-Acetylneuraminic acid (Neu5Ac) is a biomarker of cardiometabolic diseases. In the present study, we tested the hypothesis that dietary Neu5Ac may improve cardiometabolic indices. A high fat diet (HFD) + Neu5Ac (50 or 400 mg/kg BW/day) was fed to rats and compared with HFD + simvastatin (10 mg/kg BW/day) or HFD alone for 12 weeks. Weights and serum biochemicals (lipid profile, oral glucose tolerance test, leptin, adiponectin, and insulin) were measured, and mRNA levels of insulin signaling genes were determined. The results indicated that low and high doses of sialic acid (SA) improved metabolic indices, although only the oral glucose tolerance test, serum triglycerides, leptin, and adiponectin were significantly better than those in the HFD and HFD + simvastatin groups (P < 0.05). Furthermore, the results showed that only high-dose SA significantly affected the transcription of hepatic and adipose tissue insulin signaling genes. The data suggested that SA prevented HFD-induced insulin resistance in rats after 12 weeks of administration through nontranscriptionally mediated biochemical changes that may have differentially sialylated glycoprotein structures at a low dose. At higher doses, SA induced transcriptional regulation of insulin signaling genes. These effects suggest that low and high doses of SA may produce similar metabolic outcomes in relation to insulin sensitivity through multiple mechanisms. These findings are worth studying further.
Assuntos
Gorduras na Dieta/efeitos adversos , Suplementos Nutricionais , Resistência à Insulina , Ácido N-Acetilneuramínico/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Animais , Gorduras na Dieta/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Edible bird's nest (EBN) is used traditionally in many parts of Asia to improve wellbeing, but there are limited studies on its efficacy. We explored the potential use of EBN for prevention of high fat diet- (HFD-) induced insulin resistance in rats. HFD was given to rats with or without simvastatin or EBN for 12 weeks. During the intervention period, weight measurements were recorded weekly. Blood samples were collected at the end of the intervention and oral glucose tolerance test conducted, after which the rats were sacrificed and their liver and adipose tissues collected for further studies. Serum adiponectin, leptin, F2-isoprostane, insulin, and lipid profile were estimated, and homeostatic model assessment of insulin resistance computed. Effects of the different interventions on transcriptional regulation of insulin signaling genes were also evaluated. The results showed that HFD worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. Additionally, simvastatin was able to prevent hypercholesterolemia but promoted insulin resistance similar to HFD. EBN, on the other hand, prevented the worsening of metabolic indices and transcriptional changes in insulin signaling genes due to HFD. The results suggest that EBN may be used as functional food to prevent insulin resistance.
Assuntos
Aves , Dieta Hiperlipídica , Dieta , Gorduras na Dieta/metabolismo , Resistência à Insulina , Adiponectina/sangue , Animais , Produtos Biológicos , F2-Isoprostanos/sangue , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Homeostase , Insulina/sangue , Insulina/metabolismo , Leptina/sangue , Lipídeos/sangue , Medicina Tradicional Chinesa , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Transcrição GênicaRESUMO
There are reports of improved redox outcomes due to consumption of Edible Bird's Nest (EBN). Many of the functional effects of EBN can be linked to its high amounts of antioxidants. Interestingly, dietary components with high antioxidants have shown promise in the prevention of aging and its related diseases like Alzheimer's disease. In this study, the antioxidative potentials of EBN and its constituents, lactoferrin (LF) and ovotransferrin (OVF), were determined and protective effects against hydrogen peroxide (H2O2)- induced toxicity on SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and acridine orange and propidium iodide (AO/PI) staining with microscopy were examined. Results showed that EBN and its constituents attenuated H2O2-induced cytotoxicity, and decreased radical oxygen species (ROS) through increased scavenging activity. Furthermore, LF, OVF, and EBN produced transcriptional changes in antioxidant related genes that tended towards neuroprotection as compared to H2O2-treated group. Overall, the results suggest that LF and OVF may produce synergistic or all-or-none antioxidative effects in EBN.
Assuntos
Antioxidantes/farmacologia , Conalbumina/farmacologia , Lactoferrina/farmacologia , Fármacos Neuroprotetores/farmacologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Animais , Antioxidantes/isolamento & purificação , Produtos Biológicos/química , Aves , Linhagem Celular Tumoral , Conalbumina/isolamento & purificação , Expressão Gênica/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Lactoferrina/isolamento & purificação , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1RESUMO
The pathogenesis of Alzheimer's disease involves complex etiological factors, of which the deposition of beta-amyloid (Aß) protein and oxidative stress have been strongly implicated. We explored the effects of H2O2, which is a precursor for highly reactive hydroxyl radicals, on neurotoxicity and genes related to AD on neuronal cells. Candidate bioactive compounds responsible for the effects were quantified using HPLC-DAD. Additionally, the effects of germinated brown rice (GBR) on the morphology of Aß(1-42) were assessed by Transmission Electron Microscopy and its regulatory effects on gene expressions were explored. The results showed that GBR extract had several phenolic compounds and γ-oryzanol and altered the structure of Aß(1-42) suggesting an antiamyloidogenic effect. GBR was also able to attenuate the oxidative effects of H2O2 as implied by reduced LDH release and intracellular ROS generation. Furthermore, gene expression analyses showed that the neuroprotective effects of GBR were partly mediated through transcriptional regulation of multiple genes including Presenilins, APP, BACE1, BACE2, ADAM10, Neprilysin, and LRP1. Our findings showed that GBR exhibited neuroprotective properties via transcriptional regulation of APP metabolism with potential impact on Aß aggregation. These findings can have important implications for the management of neurodegenerative diseases like AD and are worth exploring further.
RESUMO
BACKGROUND: Apoptosis is often the end result of oxidative damage to neurons. Due to shared pathways between oxidative stress, apoptosis and antioxidant defence systems, an oxidative insult could end up causing cellular apoptosis or survival depending on the severity of the insult and cellular responses. Plant bioresources have received close attention in recent years for their potential role in regulating the pathways involved in apoptosis and oxidative stress in favour of cell survival. Rice bran is a bioactive-rich by-product of rice milling process. It possesses antioxidant properties, making it a promising source of antioxidants that could potentially prevent oxidative stress-induced neurodegenerative diseases. METHODS: Thus, the present study investigated the neuroprotective properties of oryzanol-rich fraction (ORF) against hydrogen peroxide (H2O2)-induced neurotoxicity in differentiated human neuroblastoma SH-SY5Y cells. ORF was extracted from rice bran using a green technology platform, supercritical fluid extraction system. Furthermore, its effects on cell viability, morphological changes, cell cycle, and apoptosis were evaluated. The underlying transcriptomic changes involved in regulation of oxidative stress, apoptosis and antioxidant defence systems were equally studied. RESULTS: ORF protected differentiated SH-SY5Y cells against H2O2-induced neurotoxicity through preserving the mitochondrial metabolic enzyme activities, thus reducing apoptosis. The mechanistic basis for the neuroprotective effects of ORF included upregulation of antioxidant genes (catalase, SOD 1 and SOD 2), downregulation of pro-apoptotic genes (JNK, TNF, ING3, BAK1, BAX, p21 and caspase-9), and upregulation of anti-apoptotic genes (ERK1/2, AKT1 and NF-Kß). CONCLUSION: These findings suggest ORF may be an effective antioxidant that could prevent oxidative stress-induced neurodegenerative disorders.
Assuntos
Peróxido de Hidrogênio/toxicidade , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenilpropionatos/farmacologia , Substâncias Protetoras/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Transcriptoma/efeitos dos fármacosRESUMO
Thymoquinone (TQ), a bioactive constituent of Nigella sativa Linn (N. sativa) has demonstrated several neuropharmacological attributes. In the present study, the neuroprotective properties of TQ were investigated by studying its anti-apoptotic potential to diminish ß-amyloid peptide 1-40 sequence (Aß1-40)-induced neuronal cell death in primary cultured cerebellar granule neurons (CGNs). The effects of TQ against Aß1-40-induced neurotoxicity, morphological damages, DNA condensation, the generation of reactive oxygen species, and caspase-3, -8, and -9 activation were investigated. Pretreatment of CGNs with TQ (0.1 and 1 µM) and subsequent exposure to 10 µM Aß1-40 protected the CGNs against the neurotoxic effects of the latter. In addition, the CGNs were better preserved with intact cell bodies, extensive neurite networks, a loss of condensed chromatin and less free radical generation than those exposed to Aß1-40 alone. TQ pretreatment inhibited Aß1-40-induced apoptosis of CGNs via both extrinsic and intrinsic caspase pathways. Thus, the findings of this study suggest that TQ may prevent neurotoxicity and Aß1-40-induced apoptosis. TQ is, therefore, worth studying further for its potential to reduce the risks of developing Alzheimer's disease.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Benzoquinonas/farmacologia , Cerebelo/patologia , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Neurotoxinas/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Células Cultivadas , Cromatina/metabolismo , DNA/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Ativação Enzimática/efeitos dos fármacos , Neuritos/efeitos dos fármacos , Neuritos/metabolismo , Neuritos/patologia , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: There are reports of improved metabolic outcomes due to consumption of germinated brown rice (GBR). Many of the functional effects of GBR can be linked to its high amounts of antioxidants. Interestingly, dietary components with high antioxidants have shown promise in the prevention of neurodegenerative diseases like Alzheimer's disease (AD). This effect of dietary components is mostly based on their ability to prevent apoptosis, which is believed to link oxidative damage to pathological changes in AD. In view of the rich antioxidant content of GBR, we studied its potential to modulate processes leading up to AD. METHODS: The total phenolic content and antioxidant capacity of the ethyl acetate extract of GBR were compared to that of brown rice (BR), and the cytotoxicity of both extracts were determined on human SH-SY5Y neuronal cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) Assay. Based on its higher antioxidant potentials, the effect of the GBR extract on morphological changes due to hydrogen peroxide (H2O2)-induced oxidative damage in human SH-SY5Y neuronal cells was examined using inverted light microscope and fluorescence microscope by means of acridine orange-propidium iodide (AO/PI) staining. Also, evaluation of the transcriptional regulation of antioxidant and apoptotic genes was carried out using Multiplex Gene Expression System. RESULTS: The ethyl acetate extract of GBR had higher total phenolic content and antioxidant capacity compared to BR. The cytotoxicity results showed that GBR extract did not cause any damage to the human SH-SY5Y neuronal cells at concentrations of up to 20 ppm, and the morphological analyses showed that the GBR extract (up to 10 ppm) prevented H2O2-induced apoptotic changes in the cells. Furthermore, multiplex gene expression analyses showed that the protection of the cells by the GBR extract was linked to its ability to induce transcriptional changes in antioxidant (SOD 1, SOD 2 and catalase) and apoptotic (AKT, NF-Kß, ERK1/2, JNK, p53 and p38 MAPK) genes that tended towards survival. CONCLUSIONS: Taken together, the results of our study showed that the ethyl acetate extract of GBR, with high antioxidant potentials, could prevent H2O2-induced oxidative damage in SH-SY5Y cells. The potential of GBR and its neuroprotective mechanism in ameliorating oxidative stress-related cytotoxicity is therefore worth exploring further.
Assuntos
Antioxidantes/farmacologia , Proteínas Reguladoras de Apoptose/genética , Apoptose/efeitos dos fármacos , Neuroblastoma/metabolismo , Fármacos Neuroprotetores/farmacologia , Oryza/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Antioxidantes/isolamento & purificação , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/metabolismo , Neuroblastoma/genética , Neuroblastoma/fisiopatologia , Fármacos Neuroprotetores/isolamento & purificação , Extratos Vegetais/isolamento & purificaçãoRESUMO
Oxidative stress is implicated in the pathogenesis of diabetic complications, and can be increased by diet like white rice (WR). Though brown rice (BR) and germinated brown rice (GBR) have high antioxidant potentials as a result of their bioactive compounds, reports of their effects on oxidative stress-related conditions such as type 2 diabetes are lacking. We hypothesized therefore that if BR and GBR were to improve antioxidant status, they would be better for rice consuming populations instead of the commonly consumed WR that is known to promote oxidative stress. This will then provide further reasons why less consumption of WR should be encouraged. We studied the effects of GBR on antioxidant status in type 2 diabetic rats, induced using a high-fat diet and streptozotocin injection, and also evaluated the effects of WR, BR and GBR on catalase and superoxide dismutase genes. As dietary components, BR and GBR improved glycemia and kidney hydroxyl radical scavenging activities, and prevented the deterioration of total antioxidant status in type 2 diabetic rats. Similarly, GBR preserved liver enzymes, as well as serum creatinine. There seem to be evidence that upregulation of superoxide dismutase gene may likely be an underlying mechanism for antioxidant effects of BR and GBR. Our results provide insight into the effects of different rice types on antioxidant status in type 2 diabetes. The results also suggest that WR consumption, contrary to BR and GBR, may worsen antioxidant status that may lead to more damage by free radicals. From the data so far, the antioxidant effects of BR and GBR are worth studying further especially on a long term to determine their effects on development of oxidative stress-related problems, which WR consumption predisposes to.
Assuntos
Antioxidantes/metabolismo , Oryza/metabolismo , Alanina Transaminase/metabolismo , Animais , Antioxidantes/química , Área Sob a Curva , Aspartato Aminotransferases/metabolismo , Glicemia/análise , Catalase/genética , Catalase/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Sequestradores de Radicais Livres/metabolismo , Germinação , Células Hep G2 , Humanos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Oryza/crescimento & desenvolvimento , Curva ROC , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Ácido gama-Aminobutírico/química , Ácido gama-Aminobutírico/metabolismoRESUMO
Diet is an important variable in the course of type 2 diabetes, which has generated interest in dietary options like germinated brown rice (GBR) for effective management of the disease among rice-consuming populations. In vitro data and animal experiments show that GBR has potentials as a functional diet for managing this disease, and short-term clinical studies indicate encouraging results. Mechanisms for antidiabetic effects of GBR due to bioactive compounds like γ-aminobutyric acid (GABA), γ-oryzanol, dietary fibre, phenolics, vitamins, acylated steryl ß-glucoside, and minerals include antihyperglycemia, low insulin index, antioxidative effect, antithrombosis, antihypertensive effect, hypocholesterolemia, and neuroprotective effects. The evidence so far suggests that there may be enormous benefits for diabetics in rice-consuming populations if white rice is replaced with GBR. However, long-term clinical studies are still needed to verify these findings on antidiabetic effects of GBR. Thus, we present a review on the antidiabetic properties of GBR from relevant preclinical and clinical studies, in order to provide detailed information on this subject for researchers to review the potential of GBR in combating this disease.