RESUMO
This study aimed to test the hypothesis that long-term and low-dose supplementation with an ethanol extract of Ecklonia stolonifera may confer protection against high-fat diet (HFD)-induced obesity in mice. Male C57BL/6J mice were divided into two groups, one of which was fed an HFD (40 kcal% fat) and the other an HFD+E. stolonifera (0.006%, w/w, â¼5 mg/kg body weight/day) for 16 weeks. E. stolonifera supplementation significantly reduced body weight from week 3 and until the end of the experiment. E. stolonifera-supplemented mice also exhibited lower fat mass (epididymal, perirenal, and mesenteric fat) and smaller adipocyte size than HFD control mice. The two groups displayed similar food intakes, but E. stolonifera markedly decreased lipogenesis and increased lipolysis and fatty acid oxidation in adipose tissue. Moreover, E. stolonifera significantly decreased plasma and hepatic lipid levels, hepatic lipid droplet accumulation, plasma aminotransferase levels, and liver weight by decreasing lipogenesis and increasing fatty acid oxidation. As E. stolonifera-supplemented mice showed improvements in hyperglycemia, insulin resistance, and inflammation, compared to control mice, it is possible that the beneficial effects of E. stolonifera on obesity might be associated with decreased inflammation and insulin resistance. Collectively, these results indicate that E. stolonifera could be used as a novel means of preventing and treating obesity and obesity-related metabolic disorders.
Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Masculino , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Camundongos Obesos , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Obesidade/tratamento farmacológico , Obesidade/etiologia , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Ácidos Graxos/metabolismoRESUMO
Temporal lobe epilepsy (TLE) is the most common form of localization-related epilepsy, with the highest prevalence rate in adulthood. Recently, we reported the beneficial effects of the individual treatment with flavonoids such as silibinin and morin in kainic acid (KA)-treated mouse model for TLE. In this study, we investigated whether there is a synergistic effect of co-treatment with silibinin and morin on the susceptibility to seizure, the frequency of spontaneous recurrent seizures (SRSs), and granule cell dispersion in the dentate gyrus, which could be partially controlled by treatment with each flavonoid in the animal model for TLE. Unfortunately, we did not observe any synergistic effect against the susceptibility of seizure and SRS induced by KA treatment. However, the combination of these flavonoids showed similar antiepileptic effects compared with treatment with each one individually. Therefore, although silibinin and morin are not suitable for combination therapy, our results still suggest that these flavonoids can be used as potent therapeutic compounds for preventing epileptic seizures.
Assuntos
Epilepsia do Lobo Temporal/tratamento farmacológico , Flavonoides/uso terapêutico , Convulsões/tratamento farmacológico , Silibina/uso terapêutico , Animais , Giro Denteado/citologia , Giro Denteado/efeitos dos fármacos , Sinergismo Farmacológico , Epilepsia do Lobo Temporal/induzido quimicamente , Ácido Caínico , Camundongos , Convulsões/induzido quimicamenteRESUMO
The flavonoid myricitrin exhibits various pharmacological and physiological effects. However, studies on the effects of myricitrin on obesity are limited. We hypothesized that dietary myricitrin would attenuate the adiposity and metabolic dysfunction that occur in obesity. To test this hypothesis, mice were randomly fed a high-fat diet (HFD) or HFD supplemented with myricitrin for 16 weeks. Myricitrin significantly reduced white adipose tissue (WAT) mass, adipocyte size, and plasma leptin levels, and also attenuated dyslipidemia. These changes appeared to result from increased energy expenditure and activation of the carnitine acyltransferase (CPT) and ß-oxidation in WAT. Expressions of the proinflammatory genes NF-κB, TLR2, MCP1, and TNF-α were also lower in the WAT of myricitrin-supplemented mice. Moreover, myricitrin markedly reduced hepatic triglyceride accumulation and plasma aspartate transaminase levels by increasing CPT activity and reducing fatty acid synthase activity in the liver. Myricitrin-supplemented mice also showed improved glucose tolerance, insulin sensitivity, and decreased hyperinsulinemia, along with decreased levels of circulating resistin. In conclusion, long-term consumption of a myricitrin-supplemented diet may effectively protect against HFD-induced obesity and related metabolic disorders.
Assuntos
Adiposidade , Suplementos Nutricionais , Flavonoides/farmacologia , Obesidade/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Dislipidemias/prevenção & controle , Fígado Gorduroso/prevenção & controle , Inflamação/prevenção & controle , Resistência à Insulina , Leptina/sangue , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/induzido quimicamenteRESUMO
Epilepsy is a chronic neurological disorder that affects many people worldwide. Temporal lobe epilepsy is the most common and most studied type of epilepsy, but the pathological mechanisms underlying this condition are poorly understood. More than 20 antiepileptic drugs (AEDs) have been developed and used for the treatment of epilepsy; however, 30% of patients still experience uncontrolled epilepsy and associated comorbidities, which impair their quality of life. In addition, various side effects have been reported for AEDs, such as drowsiness, unsteadiness, dizziness, blurred or double vision, tremor (shakiness), greater risk of infections, bruising, and bleeding. Thus, critical medical needs remain unmet for patients with uncontrolled epilepsy. Flavonoids belong to a subclass of polyphenols that are widely present in fruits, vegetables, and certain beverages. Recently, many studies have reported that some flavonoids elicit various beneficial effects in patients with epilepsy without causing the side effects associated with conventional medical therapies. Moreover, flavonoids may have a property of regulating microRNA expression associated with inflammation and cell survival. These findings suggest that flavonoids, which are more effective but impose fewer adverse effects than conventional AEDs, could be used in the treatment of epilepsy.
Assuntos
Anticonvulsivantes/uso terapêutico , Terapias Complementares/métodos , Epilepsia/terapia , Flavonoides/uso terapêutico , HumanosRESUMO
We hypothesized that schizandrin (SCH) A, a lignan found in the fruits of the Schisandra genus, would exert protective effects against high-fat and high-cholesterol (HFHC) diet-induced nonalcoholic fatty liver disease (NAFLD) via regulation of lipid metabolism and oxidative stress. To test our hypothesis, male C57BL/6J mice were fed an HFHC diet with or without SCH A for 15â¯weeks. There were no significant differences in food intake, body weight, fat mass, and plasma total cholesterol level between the 2 groups. However, supplementation of SCH A significantly decreased levels of plasma free fatty acid and triglyceride, whereas plasma high-density lipoprotein cholesterol level was increased in the SCH A-supplemented mice. Moreover, hepatic free fatty acid, triglyceride, and cholesterol content, as well as hepatic lipid droplet accumulation, were markedly lower in the SCH A group in contrast to the control group. Activity of hepatic enzymes involved in fatty acid and triglyceride synthesis was significantly decreased by SCH A supplementation, whereas SCH A markedly increased hepatic ß-oxidation and fatty acid oxidation-related gene expression as well as fecal excretion of free fatty acid and triglyceride. SCH A also significantly increased expression of genes involved in cholesterol homeostasis (biliary cholesterol excretion and cholesterol efflux to high-density lipoprotein) in the liver. Moreover, SCH A significantly decreased hepatic lipid peroxidation, which was accompanied by increased hepatic antioxidant enzymes activity. These results suggest that SCH A could alleviate HFHC diet-induced NAFLD by regulating hepatic lipid metabolism and oxidative stress as well as fecal lipid excretion.
Assuntos
Colesterol na Dieta/metabolismo , Ciclo-Octanos/uso terapêutico , Lignanas/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Compostos Policíclicos/uso terapêutico , Schisandra/química , Animais , Antioxidantes/metabolismo , Colesterol/sangue , Colesterol/metabolismo , Colesterol na Dieta/administração & dosagem , Colesterol na Dieta/efeitos adversos , Colesterol na Dieta/sangue , HDL-Colesterol/sangue , Ciclo-Octanos/farmacologia , Dieta Hiperlipídica , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/metabolismo , Suplementos Nutricionais , Ácidos Graxos/metabolismo , Ácidos Graxos não Esterificados/sangue , Fezes/química , Lignanas/farmacologia , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Compostos Policíclicos/farmacologia , Triglicerídeos/sangueRESUMO
Parkinson's disease (PD) and Alzheimer's disease exhibit common features of neurodegenerative diseases and can be caused by numerous factors. A common feature of these diseases is neurotoxic inflammation by activated microglia, indicating that regulation of microglial activation is a potential mechanism for preserving neurons in the adult brain. Recently, we reported that upregulation of prothrombin kringle-2 (pKr-2), one of the domains that make up prothrombin and which is cleaved and generated by active thrombin, induces nigral dopaminergic (DA) neuronal death through neurotoxic microglial activation in the adult brain. In this study, we show that silibinin, a flavonoid found in milk thistle, can suppress the production of inducible nitric oxide synthase and neurotoxic inflammatory cytokines, such as interleukin-1ß and tumor necrosis factor-α, after pKr-2 treatment by downregulating the extracellular signal-regulated kinase signaling pathway in the mouse substantia nigra. Moreover, as demonstrated by immunohistochemical staining, measurements of the dopamine and metabolite levels, and open-field behavioral tests, silibinin treatment protected the nigrostriatal DA system resulting from the occurrence of pKr-2-triggered neurotoxic inflammation in vivo. Thus, we conclude that silibinin may be beneficial as a natural compound with anti-inflammatory effects against pKr-2-triggered neurotoxicity to protect the nigrostriatal DA pathway and its properties, and thus, may be applicable for PD therapy.
Assuntos
Dopamina/metabolismo , Doença de Parkinson/tratamento farmacológico , Protrombina/toxicidade , Silibina/administração & dosagem , Animais , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Kringles , Masculino , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Protrombina/química , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Abnormal reorganization of the dentate gyrus and neuroinflammation in the hippocampus represent characteristic phenotypes of patients suffering from temporal lobe epilepsy. Hesperetin, a flavanone abundant in citrus fruit, is known to have protective effects by preventing inflammation and oxidative stress in neuronal cultures and in the adult murine brain. However, the protective effects of hesperetin against epileptic seizures in vivo remain unclear, despite one study reporting anticonvulsant effects in vitro. In this study, we report that oral administration of hesperetin not only delays the onset of seizures triggered by kainic acid (KA) but also contributes to the attenuation of granule cell dispersion in the KA-treated hippocampus. Moreover, we observed that hesperetin administration inhibited the expression of pro-inflammatory molecules produced by activated microglia in the hippocampus. Thus, administration of hesperetin might be beneficial for preventing epileptic seizures.
Assuntos
Anticonvulsivantes/uso terapêutico , Citrus , Epilepsia do Lobo Temporal/tratamento farmacológico , Hesperidina/uso terapêutico , Fitoterapia , Administração Oral , Animais , Anticonvulsivantes/administração & dosagem , Modelos Animais de Doenças , Epilepsia do Lobo Temporal/induzido quimicamente , Frutas , Hesperidina/administração & dosagem , Ácido Caínico , Masculino , CamundongosRESUMO
Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta and decreases in striatal dopamine levels. These changes led to several clinical symptoms: rigidity, resting tremor, and bradykinesia. Although the cause of PD remains unclear, it is widely accepted that oxidative stress, neuroinflammation, mitochondrial dysfunction, and insufficient support of neurotrophic factors are involved in the pathophysiology of the disease. However, novel regimens to prevent neurodegeneration and restore the degenerated nigrostriatal DA system are still required. In recent years, there has been a growing interest in naturally occurring phytochemicals, which are believed to reduce the risk of neurodegenerative diseases. This review provides an overview of the scientific literature concerning the preventive and protective roles of flavonoids, one of the largest families of phytochemicals, against PD. In addition to providing antioxidant and anti-inflammatory effects, flavonoids exhibit a neuroprotective effect by activating antiapoptotic pathways that target mitochondrial dysfunction and induce neurotrophic factors. This review suggests that flavonoids may be promising natural products for the prevention of PD and could potentially be utilized as therapeutic compounds against PD, even though there was no report showing that the treatment with flavonoids could restore the aberrant phenotypes of patients with PD.
Assuntos
Flavonoides/farmacologia , Doença de Parkinson/tratamento farmacológico , Animais , Antocianinas/farmacologia , Antioxidantes/farmacologia , Antiparkinsonianos/farmacologia , Catequina/análogos & derivados , Catequina/farmacologia , Linhagem Celular , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Flavanonas/farmacologia , Flavonas/farmacologia , Flavonóis/farmacologia , Humanos , Isoflavonas/farmacologia , Quempferóis/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
This study evaluated whether long-term supplementation with dietary yerba mate has beneficial effects on adiposity and its related metabolic dysfunctions in diet-induced obese mice. C57BL/6J mice were randomly divided into two groups and fed their respective experimental diets for 16 weeks as follows: (1) control group fed with high-fat diet (HFD) and (2) mate group fed with HFD plus yerba mate. Dietary yerba mate increased energy expenditure and thermogenic gene mRNA expression in white adipose tissue (WAT) and decreased fatty acid synthase (FAS) mRNA expression in WAT, which may be linked to observed decreases in body weight, WAT weight, epididymal adipocyte size, and plasma leptin level. Yerba mate also decreased levels of plasma lipids (free fatty acids, triglycerides, and total cholesterol) and liver aminotransferase enzymes, as well as the accumulation of hepatic lipid droplets and lipid content by inhibiting the activities of hepatic lipogenic enzymes, such as FAS and phosphatidate phosphohydrolase, and increasing fecal lipid excretion. Moreover, yerba mate decreased the levels of plasma insulin as well as the homeostasis model assessment of insulin resistance, and improved glucose tolerance. Circulating levels of gastric inhibitory polypeptide and resistin were also decreased in the mate group. These findings suggest that long-term supplementation of dietary yerba mate may be beneficial for improving diet-induced adiposity, insulin resistance, dyslipidemia, and hepatic steatosis.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Ilex paraguariensis/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Doenças Metabólicas/tratamento farmacológico , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais/análise , Humanos , Masculino , Doenças Metabólicas/metabolismo , Doenças Metabólicas/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/fisiopatologiaRESUMO
The aim of the current study was to elucidate the effect of seabuckthorn leaves (SL) extract and flavonoid glycosides extract from seabuckthorn leaves (SLG) on diet-induced obesity and related metabolic disturbances, and additionally, to identify whether flavonoid glycosides and other components in SL can exert a possible interaction for the prevention of metabolic diseases by comparing the effect of SL and SLG. C57BL/6J mice were fed a normal diet (ND, AIN-93G purified diet), high-fat diet (HFD, 60 kcal% fat), HFD + 1.8% (w/w) SL (SL), and HFD + 0.04% (w/w) SLG (SLG) for 12 weeks. In high fat-fed mice, SL and SLG decreased the adiposity by suppressing lipogenesis in adipose tissue, while increasing the energy expenditure. SL and SLG also improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption, whilst also enhancing hepatic fatty acid oxidation, which may be linked to the improvement in dyslipidemia. Moreover, SL and SLG improved insulin sensitivity by suppressing the levels of plasma GIP that were modulated by secreted resistin and pro-inflammatory cytokine, and hepatic glucogenic enzyme activities. SL, especially its flavonoid glycosides (SLG), can protect against the deleterious effects of diet-induced obesity (DIO) and its metabolic complications such as adiposity, dyslipidemia, inflammation, hepatic steatosis, and insulin resistance.
Assuntos
Adiposidade/efeitos dos fármacos , Fígado Gorduroso/tratamento farmacológico , Flavonoides/farmacologia , Resistência à Insulina , Fitoterapia , Extratos Vegetais/farmacologia , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético , Hippophae/química , Inflamação/tratamento farmacológico , Inflamação/etiologia , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Folhas de Planta/químicaRESUMO
SCOPE: We evaluated the long-term effect of low-dose nobiletin (NOB), a polymethoxylated flavone, on diet-induced obesity and related metabolic disturbances. METHODS AND RESULTS: C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without NOB (0.02%, w/w) for 16 weeks. NOB did not alter food intake or body weight. Despite increases in fatty acid oxidation-related genes expression and enzymes activity in adipose tissue, NOB did not affect adipose tissue weight due to simultaneous increases in lipogenic genes expression and fatty acid synthase activity. However, NOB significantly decreased not only pro-inflammatory genes expression in adipose tissue but also proinflammatory cytokine levels in plasma. NOB-supplemented mice also showed improved glucose tolerance and insulin resistance, along with decreased levels of plasma insulin, free fatty acids, total cholesterol, non-HDL-cholesterol, and apolipoprotein B. In addition, NOB caused significant decreases in hepatic lipid droplet accumulation and triglyceride content by activating hepatic fatty acid oxidation-related enzymes. Hepatic proinflammatory TNF-α mRNA expression, collagen accumulation, and plasma levels of aminotransferases, liver damage indicators, were also significantly lower in NOB-supplemented mice. CONCLUSION: These findings suggest that long-term supplementation with low-dose NOB can protect against HFD-induced inflammation, insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease, without ameliorating adiposity.
Assuntos
Flavonas/administração & dosagem , Hepatite/dietoterapia , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Obesidade/complicações , Tecido Adiposo/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Citocinas/sangue , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Dislipidemias/dietoterapia , Dislipidemias/etiologia , Flavonas/farmacologia , Hepatite/etiologia , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/etiologiaRESUMO
This study investigated the biological and molecular mechanisms underlying the antiobesity effect of omija fruit ethanol extract (OFE) in mice fed a high-fat diet (HFD). C57BL/6J mice were fed an HFD (20% fat, w/w) with or without OFE (500 mg/kg body weight) for 16 weeks. Dietary OFE significantly increased brown adipose tissue weight and energy expenditure while concomitantly decreasing white adipose tissue (WAT) weight and adipocyte size by up-regulating the expression of brown fat-selective genes in WAT. OFE also improved hepatic steatosis and dyslipidemia by enhancing hepatic fatty acid oxidation-related enzymes activity and fecal lipid excretion. In addition to steatosis, OFE decreased the expression of pro-inflammatory genes in the liver. Moreover, OFE improved glucose tolerance and lowered plasma glucose, insulin and homeostasis model assessment of insulin resistance, which may be linked to decreases in the activity of hepatic gluconeogenic enzymes and the circulating level of gastric inhibitory polypeptide. These findings suggest that OFE may protect against diet-induced adiposity and related metabolic disturbances by controlling brown-like transformation of WAT, fatty acid oxidation, inflammation in the liver and fecal lipid excretion. Improved insulin resistance may be also associated with its antiobesity effects.
Assuntos
Adiposidade , Fármacos Antiobesidade/uso terapêutico , Suplementos Nutricionais , Resistência à Insulina , Sobrepeso/prevenção & controle , Extratos Vegetais/uso terapêutico , Schisandra/química , Tecido Adiposo Bege/imunologia , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Bege/patologia , Tecido Adiposo Branco/imunologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Animais , Biomarcadores/sangue , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético , Etanol/química , Frutas/química , Regulação Enzimológica da Expressão Gênica , Fígado/enzimologia , Fígado/imunologia , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Sobrepeso/imunologia , Sobrepeso/metabolismo , Sobrepeso/patologia , Distribuição Aleatória , Solventes/química , Aumento de PesoRESUMO
Pterocarpans are known to have antifungal and anti-inflammatory properties. However, little is known about the changes in transcriptional profiles in response to a pterocarpan-high soybean leaf extract (PT). Therefore, this study investigated the effects of PT on blood glucose and lipid levels, as well as on the inflammation-related gene expression based on a peripheral blood mononuclear cells (PBMCs) mRNA sequencing analysis in Korean overweight and obese subjects with mild metabolic syndrome. The participants were randomly assigned to two groups and were administered either placebo (starch, 3 g/day) or PT (2 g/day) for 12 weeks. The PT intervention did not change body weight, body fat percentage and body mass index (BMI). However, PT significantly decreased the glycosylated hemoglobin (HbA1c), plasma glucose, free fatty acid, total cholesterol, and non-HDL cholesterol levels after 12 weeks. Furthermore, PT supplementation significantly lowered the homeostatic index of insulin resistance, as well as the plasma levels of inflammatory markers. Finally, the mRNA sequencing analysis revealed that PT downregulated genes related to immune responses. PT supplementation is beneficial for the improvement of metabolic syndrome by altering the fasting blood and plasma glucose, HbA1c, plasma lipid levels and inflammation-related gene expression in PBMCs.
Assuntos
Glycine max/química , Síndrome Metabólica/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Pterocarpanos/uso terapêutico , Adulto , Idoso , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Método Duplo-Cego , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Humanos , Mediadores da Inflamação/sangue , Resistência à Insulina , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/genética , Pessoa de Meia-Idade , Sobrepeso/sangue , Sobrepeso/diagnóstico , Sobrepeso/genética , Fitoterapia , Extratos Vegetais/efeitos adversos , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Pterocarpanos/efeitos adversos , Pterocarpanos/isolamento & purificação , República da Coreia , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Resultado do TratamentoRESUMO
Granule cell dispersion (GCD) in the dentate gyrus (DG) of the hippocampus is a morphological alteration characteristic of temporal lobe epilepsy. Recently, we reported that treatment with naringin, a flavonoid found in grapefruit and citrus fruits, reduced spontaneous recurrent seizures by inhibiting kainic acid (KA)-induced GCD and neuronal cell death in mouse hippocampus, suggesting that naringin might have beneficial effects for preventing epileptic events in the adult brain. However, it is still unclear whether the beneficial effects of naringin treatment are mediated by the metabolism of naringin into naringenin in the KA-treated hippocampus. To investigate this possibility, we evaluated whether intraperitoneal injections of naringenin could mimic naringin-induced effects against GCD caused by intrahippocampal KA injections in mice. Our results showed that treatment with naringenin delayed the onset of KA-induced seizures and attenuated KA-induced GCD by inhibiting activation of the mammalian target of rapamycin complex 1 in both neurons and reactive astrocytes in the DG. In addition, its administration attenuated the production of proinflammatory cytokines such as tumor necrosis tumor necrosis factor-α (TNFα) and interleukin-1ß (IL-1ß) from microglial activation in the DG following KA treatment. These results suggest that naringenin may be an active metabolite of naringin and help prevent the progression of epileptic insults in the hippocampus in vivo; therefore, naringenin may be a beneficial metabolite of naringin for the treatment of epilepsy.
Assuntos
Anticonvulsivantes/uso terapêutico , Giro Denteado/efeitos dos fármacos , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia do Lobo Temporal/patologia , Flavanonas/uso terapêutico , Proteínas Adaptadoras de Transdução de Sinal , Animais , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular , Citocinas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Epilepsia do Lobo Temporal/induzido quimicamente , Fatores de Iniciação em Eucariotos , Agonistas de Aminoácidos Excitatórios/toxicidade , Ácido Caínico/toxicidade , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Fosfoproteínas/metabolismoRESUMO
Parkinson's disease (PD) is a chronic and progressive movement disorder, resulting from the degeneration of the nigrostriatal dopaminergic (DA) pathway. The cause of DA neuronal loss in PD is still unclear; however, accumulating evidence suggests that treatment with certain flavonoids can induce neuroprotective properties, such as activation of mammalian target of rapamycin complex 1 (mTORC1) and anti-inflammatory activities in animal models of PD. The bioflavonoid myricitrin is well known for its anti-inflammatory and antioxidant properties. However, it is unclear whether systemic treatment with myricitrin can protect neurons against neurotoxin-induced DA degeneration in vivo via the preservation of tyrosine hydroxylase (TH) activity and the induction of mTORC1 activation. Our results found no significant neuroprotective effect of 30 mg/kg myricitrin on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in the substantia nigra (SN) of mice. However, myricitrin treatment with 60 mg/kg protected DA neurons against 6-OHDA-induced neurotoxicity. Moreover, myricitrin treatment preserved TH enzyme activity and mTORC1 activation in nigral DA neurons in the SN of 6-OHDA-treated mice, and its treatment suppressed an increase in tumor necrosis factor-α expression in activated microglia. These results suggest that myricitrin may have neuroprotective properties linked to mTORC1 activation, preservation of TH enzyme activity, and anti-neuroinflammation for preventing DA neuronal degeneration in vivo.
Assuntos
Neurônios Dopaminérgicos/citologia , Flavonoides/farmacologia , Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , Doença de Parkinson/tratamento farmacológico , Animais , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Substância Negra/citologia , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
We recently reported that treatment with naringin, a major flavonoid found in grapefruit and citrus fruits, attenuated neurodegeneration in a rat model of Parkinson's disease (PD) in vivo. In order to investigate whether its effects are universally applied to a different model of PD and whether its treatment induces restorative effects on the lesioned nigrostriatal dopaminergic (DA) projection, we observed the effects of pre-treatment or post-treatment with naringin in a mouse model of PD. For neuroprotective effects, 6-hydroxydopamine (6-OHDA) was unilaterally injected into the striatum of mouse brains for a neurotoxin model of PD in the presence or absence of naringin by daily intraperitoneal injection. Our results showed that naringin protected the nigrostriatal DA projection from 6-OHDA-induced neurotoxicity. Moreover, similar to the effects in rat brains, this treatment induced the activation of mammalian target of rapamycin complex 1 (mTORC1), which is well known as an important survival factor for DA neurons, and inhibited microglial activation in the substantia nigra (SN) of mouse brains treated with 6-OHDA. However, there was no significant change of DA phenotypes in the SN and striatum post-treated with naringin compared with 6-OHDA-lesioned mice, despite the treatment being continued for 12 weeks. These results suggest that post-treatment with naringin alone may not be enough to restore the nigrostriatal DA projection in a mouse model of PD. However, our results apparently suggest that naringin is a beneficial natural product to prevent DA degeneration, which is involved in PD.
Assuntos
Modelos Animais de Doenças , Dopamina/metabolismo , Flavanonas/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Animais , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Oxidopamina/administração & dosagem , Doença de Parkinson/patologiaRESUMO
Obesity, along with its related complications, is a serious health problem worldwide. Many studies reported the anti-diabetic effect of phlorizin, while little is known about its anti-obesity effect. We investigated the beneficial effects of phlorizin on obesity and its complications, including diabetes and inflammation in obese animal. Male C57BL/6J mice were divided into three groups and fed their respective experimental diets for 16 weeks: a normal diet (ND, 5% fat, w/w), high-fat diet (HFD, 20% fat, w/w), or HFD supplemented with phlorizin (PH, 0.02%, w/w). The findings revealed that the PH group had significantly decreased visceral and total white adipose tissue (WAT) weights, and adipocyte size compared to the HFD. Plasma and hepatic lipids profiles also improved in the PH group. The decreased levels of hepatic lipids in PH were associated with decreased activities of enzymes involved in hepatic lipogenesis, cholesterol synthesis and esterification. The PH also suppressed plasma pro-inflammatory adipokines levels such as leptin, adipsin, tumor necrosis factor-α, monocyte chemoattractant protein-1, interferon-γ, and interleukin-6, and prevented HFD-induced collagen accumulation in the liver and WAT. Furthermore, the PH supplementation also decreased plasma glucose, insulin, glucagon, and homeostasis model assessment of insulin resistance levels. In conclusion, phlorizin is beneficial for preventing diet-induced obesity, hepatic steatosis, inflammation, and fibrosis, as well as insulin resistance.
Assuntos
Tecido Adiposo/efeitos dos fármacos , Suplementos Nutricionais , Hiperglicemia/tratamento farmacológico , Inflamação/tratamento farmacológico , Fígado/efeitos dos fármacos , Obesidade/tratamento farmacológico , Florizina/uso terapêutico , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Dieta Hiperlipídica , Hiperglicemia/sangue , Hiperglicemia/etiologia , Inflamação/etiologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Malus/química , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/complicações , Obesidade/metabolismo , Florizina/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
SCOPE: A number of findings suggest that zero-calorie d-allulose, also known as d-psicose, has beneficial effects on obesity-related metabolic disturbances. However, it is unclear whether d-allulose can normalize the metabolic status of diet-induced obesity without having an impact on the energy density. We investigated whether 5% d-allulose supplementation in a high fat diet(HFD) could normalize body fat in a diet-induced obesity animal model under isocaloric pair-fed conditions. METHODS AND RESULTS: Mice were fed an HFD with or without various sugar substitutes (d-glucose, d-fructose, erytritol, or d-allulose, n = 10 per group) for 16 wk. Body weight and fat-pad mass in the d-allulose group were dramatically lowered to that of the normal group with a simultaneous decrease in plasma leptin and resistin concentrations. d-allulose lowered plasma and hepatic lipids while elevating fecal lipids with a decrease in mRNA expression of CD36, ApoB48, FATP4, in the small intestine in mice. In the liver, activities of both fatty acid synthase and ß-oxidation were downregulated by d-allulose to that of the normal group; however, in WAT, fatty acid synthase was decreased while ß-oxidation activity was enhanced. CONCLUSION: Taken together, our findings suggest that 5% dietary d-allulose led to the normalization of the metabolic status of diet-induced obesity by altering lipid-regulating enzyme activities and their gene-expression level along with fecal lipids.
Assuntos
Peso Corporal/efeitos dos fármacos , Frutose/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Adiposidade/efeitos dos fármacos , Animais , Apolipoproteína B-48/genética , Apolipoproteína B-48/metabolismo , Glicemia/metabolismo , Antígenos CD36/genética , Antígenos CD36/metabolismo , Dieta Hiperlipídica , Suplementos Nutricionais , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Regulação da Expressão Gênica , Glucose/administração & dosagem , Leptina/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Resistina/sangue , Edulcorantes/administração & dosagemRESUMO
The aim of this study was to examine the efficacy of combined grape pomace and omija fruit ethanol extracts (GO) on metabolic disorders in overweight or obese subjects. Seventy-six subjects (30-70 years, body mass index ≥23.0 kg/m2) were divided into control (starch, 4 g/day, n = 24), low-GO (low dose GO, grape pomace extract [342.5 mg/day] + omija fruit extract [57.5 mg/day], n = 26), and high-GO (high dose GO, grape pomace extract [685 mg/day] + omija fruit extract [115 mg/day], n = 26) groups. Body composition, nutrient intake, plasma lipid profiles, inflammation, antioxidant capacity, and hepatotoxicity markers were assessed in all subjects at the baseline and 10 weeks after taking the supplements. The body weight and body fat of overweight or obese subjects was not significantly altered in the low-GO and high-GO groups. However, the high-GO supplement significantly decreased the baseline-adjusted final plasma total-cholesterol, low-density lipoprotein (LDL)-cholesterol, and non-high-density lipoprotein (HDL)-cholesterol levels and increased the baseline-adjusted final plasma apolipoprotein (apo) A-1 level compared with that of the control group. In addition, the high-GO supplement significantly lowered apo B, apo B/apo A-1, lipoprotein a (Lp[a]), atherogenic index, interleukin (IL)-1ß, tumor necrosis factor-α, and elevated erythrocyte antioxidant capacity compared with the control group or the baseline levels. The low-GO supplement decreased the plasma IL-1ß level and elevated erythrocyte superoxide dismutase activity compared with that at baseline. However, in general, high-GO exerted a greater effect than low-GO. There were no significant differences in activities of plasma glutamate oxaloacetate transaminase and glutamate pyruvate transaminase between the groups. This study is a preliminary clinical study to verify that GO could be beneficial for amelioration of obesity-related dyslipidemia, inflammation, and oxidative stress without side effect in the overweight or obese subjects.
Assuntos
Composição Corporal/efeitos dos fármacos , Suplementos Nutricionais , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Extratos Vegetais/farmacologia , Vitis/química , Adulto , Idoso , Antioxidantes/metabolismo , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Biomarcadores/sangue , Índice de Massa Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Frutas/química , Humanos , Interleucina-1beta/sangue , Interleucina-6/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
Grape products have been known to exert greater antioxidant and anti-obesity than anti-hyperglycemic effects in animals and humans. Omija is used as an ingredient in traditional medicine, and it is known to have an anti-hyperglycemic effect. We investigated whether the combined extracts of grape pomace and omija fruit (GE+OE) could reduce fat accumulation in adipose and hepatic tissues and provide beneficial effects against hyperglycemia and insulin resistance in type 2 diabetic mice. C57BL/KsJ-db/db mice were fed either a normal control diet or GE+OE (0.5% grape pomace extract and 0.05% omija fruit extract, w/w) for 7 weeks. GE+OE decreased plasma leptin and resistin levels while increasing adiponectin levels and reducing the total white adipose tissue weight. Furthermore, GE+OE lowered plasma free fatty acid (FFA), triglyceride, and total-cholesterol levels as well as hepatic FFA and cholesterol levels. Hepatic fatty acid synthase and glucose 6-phosphate dehydrogenase activities were decreased in the GE+OE group, whereas hepatic ß-oxidation activity was increased. Furthermore, GE+OE supplementation not only reduced hyperglycemia and pancreatic ß-cell failure but also lowered blood glycosylated hemoglobin and plasma insulin levels. The homeostasis model assessment of insulin resistance levels was also decreased and the decrease seems to be mediated by the lowered activities of hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinases. The present data suggest that GE+OE may have the potential to reduce hyperglycemia, insulin resistance, and obesity in patients with type 2 diabetes.