Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
Add more filters










Database
Language
Publication year range
1.
FASEB J ; 31(11): 4998-5011, 2017 11.
Article in English | MEDLINE | ID: mdl-28739640

ABSTRACT

Obesity, which is caused by an energy imbalance between calorie intake and consumption, has become a major international health burden. Obesity increases the risk of insulin resistance and age-related cognitive decline, accompanied by peripheral inflammation. (-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, possesses antioxidant, anti-inflammatory, and cardioprotective activities; however, few reports have focused on its potential effect on cognitive disorders. In this study, our goal was to investigate the protective effects of EGCG treatment on insulin resistance and memory impairment induced by a high-fat and high-fructose diet (HFFD). We randomly assigned 3-mo-old C57BL/6J mice to 3 groups with different diets: control group, HFFD group, and HFFD plus EGCG group. Memory loss was assessed by using the Morris water maze test, during which EGCG was observed to prevent HFFD-elicited memory impairment and neuronal loss. Consistent with these results, EGCG attenuated HFFD-induced neuronal damage. Of note, EGCG significantly ameliorated insulin resistance and cognitive disorder by up-regulating the insulin receptor substrate-1 (IRS-1)/AKT and ERK/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathways. Long-term HFFD-triggered neuroinflammation was restored by EGCG supplementation by inhibiting the MAPK and NF-κB pathways, as well as the expression of inflammatory mediators, such as TNF-α. EGCG also reversed high glucose and glucosamine-induced insulin resistance in SH-SY5Y neuronal cells by improving the oxidized cellular status and mitochondrial function. To our knowledge, this study is the first to provide compelling evidence that the nutritional compound EGCG has the potential to ameliorate HFFD-triggered learning and memory loss.-Mi, Y., Qi, G., Fan, R., Qiao, Q., Sun, Y., Gao, Y., Liu, X. EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS.


Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Catechin/analogs & derivatives , Cyclic AMP Response Element-Binding Protein/metabolism , Dietary Carbohydrates/adverse effects , Dietary Fats/adverse effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Fructose/adverse effects , Insulin Receptor Substrate Proteins/metabolism , Learning Disabilities/metabolism , MAP Kinase Signaling System/drug effects , Memory Disorders/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Animals , Catechin/pharmacology , Cell Line , Dietary Carbohydrates/pharmacology , Dietary Fats/pharmacology , Fructose/pharmacology , Learning Disabilities/chemically induced , Learning Disabilities/pathology , Memory Disorders/chemically induced , Memory Disorders/pathology , Mice
2.
Sci Rep ; 7: 45728, 2017 04 04.
Article in English | MEDLINE | ID: mdl-28374807

ABSTRACT

Sesamol, a nutritional phenolic antioxidant compound enriched in sesame seeds, has been shown to have potential anticancer activities. This study aims at characterizing the antitumor efficacy of sesamol and unveiling the importance of mitochondria in sesamol-induced effects using a human hepatocellular carcinoma cell line, HepG2 cells. Results of this study showed that sesamol treatment suppressed colony formation, elicited S phase arrest during cell cycle progression, and induced both intrinsic and extrinsic apoptotic pathway in vitro with a dose-dependent manner. Furthermore, sesamol treatment elicited mitochondrial dysfunction by inducing a loss of mitochondrial membrane potential. Impaired mitochondria and accumulated H2O2 production resulted in disturbance of redox-sensitive signaling including Akt and MAPKs pathways. Mitochondrial biogenesis was inhibited as suggested by the decline in expression of mitochondrial complex I subunit ND1, and the upstream AMPK/PGC1α signals. Importantly, sesamol inhibited mitophagy and autophagy through impeding the PI3K Class III/Belin-1 pathway. Autophagy stimulator rapamycin reversed sesamol-induced apoptosis and mitochondrial respiration disorders. Moreover, it was also shown that sesamol has potent anti-hepatoma activity in a xenograft nude mice model. These data suggest that mitochondria play an essential role in sesamol-induced HepG2 cells death, and further research targeting mitochondria will provide more chemotherapeutic opportunities.


Subject(s)
Antioxidants/pharmacology , Apoptosis/drug effects , Autophagy/drug effects , Benzodioxoles/pharmacology , Phenols/pharmacology , Animals , Carcinoma, Hepatocellular/metabolism , Cell Proliferation/drug effects , Hep G2 Cells , Humans , Liver Neoplasms/metabolism , Male , Membrane Potential, Mitochondrial/drug effects , Mice, Nude , Mitochondria/drug effects , Mitochondria/metabolism , Sirolimus/pharmacology , Xenograft Model Antitumor Assays
3.
Food Funct ; 8(2): 710-719, 2017 Feb 22.
Article in English | MEDLINE | ID: mdl-28102395

ABSTRACT

Sesamol, a nutritional component from sesame, possesses antioxidant, lipid lowering and antidepressant activities. Nonetheless, few studies report its effects on high-energy-dense diet-induced cognitive loss. The present research aimed to elucidate the action of sesamol on high-fat and high-fructose (HFFD) "western"-diet-induced central nervous system insulin resistance and learning and memory impairment, and further determined the possible underlying mechanism. 3 month-old C57BL/6J mice were divided into 3 groups with/without sesamol in the drinking water (0.05%, w/v) and standard diet, HFFD, and HFFD with sesamol supplementation. Morris water maze tests demonstrated that sesamol improved HFFD-elicited learning and memory loss. Sesamol was also found to attenuate neuron damage in HFFD-fed mice. Importantly, sesamol treatment up-regulated brain insulin signaling by stimulating IRS-1/AKT as well as ERK/CREB/BDNF pathways; meanwhile it down-regulated neuronal death signaling GSK3ß and JNK. Moreover, sesamol also normalized mRNA expressions of neurotrophins including BDNF and NT-3, as well as expressions of mitochondrial metabolic and biogenesis related genes Sirt1 and PGC1α. Consistently, sesamol also reversed high-glucose-induced oxidized cellular status, mitochondrial membrane potential loss, insulin signaling inhibition and cell death in SH-SY5Y neuronal cells. Taken together, the current study proved that sesamol reduced western-diet-induced cognitive defects in a mouse model by inhibiting insulin resistance, normalizing mitochondrial function and cell redox status, and improving IRS/AKT cell surviving and energy metabolism regulating signaling. This compelling evidence indicated that sesamol is a potential nutritional supplement to prevent unhealthy-diet-induced learning and memory loss.


Subject(s)
Benzodioxoles/administration & dosage , Cognition Disorders/drug therapy , Diet, High-Fat/adverse effects , Fructose/adverse effects , Insulin/metabolism , Nervous System/drug effects , Phenols/administration & dosage , Animals , Cognition/drug effects , Cognition Disorders/etiology , Cognition Disorders/physiopathology , Cognition Disorders/psychology , Dietary Supplements/analysis , Humans , Male , Mice , Mice, Inbred C57BL , Nervous System/metabolism , Nervous System/physiopathology , Signal Transduction/drug effects , Sirtuin 1/genetics , Sirtuin 1/metabolism
4.
Mol Nutr Food Res ; 61(8)2017 08.
Article in English | MEDLINE | ID: mdl-28012248

ABSTRACT

SCOPE: The aim of the current study was to investigate the effect of sesamol, a natural powerful antioxidant and anti-inflammatory phenol derivative of sesame oil, on adiposity and adiposity-related metabolic disturbances in mice fed with western diet, and the potential underlying mechanisms focusing on the mitochondria-lipid metabolism. METHODS AND RESULTS: In the experimental model that consisted of 3-month-old C57BL/6J mice divided into three groups with/without sesamol in the drinking water including standard diet, high fat and high fructose diet (HFFD), and HFFD with sesamol. Results demonstrated that sesamol mitigated bodyweight gain, development of insulin resistance induced by HFFD. Sesamol was found partially normalized serum and hepatic lipid contents, as well as suppressed HFFD-induced lipogenesis in liver via regulating mitochondria-related triglyceride/cholesterol metabolism genes expressions. Importantly, sesamol decreased mass and adipocyte sizes of white adipose tissues and brown adipose tissues by improving mitochondria-related genes expressions including Pgc1a and Ucp1. Moreover, sesamol was also found to reduce differentiation and mitochondrial metabolic inhibitors (oligomycin and antimycin A) stimulated lipid accumulation in 3T3-L1 adipocytes. CONCLUSION: Taken together, this study provides compelling evidence that sesamol supplementation reduced adipocyte size and adipogenesis of diet-induced obesity by regulating mitochondria lipid metabolism.


Subject(s)
Adipogenesis/drug effects , Benzodioxoles/pharmacology , Lipid Metabolism/drug effects , Mitochondria/drug effects , Obesity/diet therapy , Phenols/pharmacology , 3T3-L1 Cells , Adipose Tissue, White/drug effects , Adipose Tissue, White/metabolism , Animals , Body Weight/drug effects , Diet, High-Fat/adverse effects , Gene Expression Regulation , Insulin Resistance , Lipid Metabolism/genetics , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Mitochondria/metabolism , Mitochondria, Liver/drug effects , Mitochondria, Liver/genetics , Obesity/etiology
5.
Mol Nutr Food Res ; 61(5)2017 05.
Article in English | MEDLINE | ID: mdl-27860258

ABSTRACT

SCOPE: The aim of the present study was to investigate the inhibitory effects of sesamol, a phenolic lignan from sesame, on the systemic inflammation-induced neuroinflammation and amyloidogenesis as well as memory impairment. METHODS AND RESULTS: C57BL/6J mice were treated with 0.05% sesamol (w/v) in the drinking water for 7 weeks, and then the mice were treated by intraperitoneal injection of LPS (0.25 mg/kg) for 9 days. Sesamol supplementation significantly improved (by 36.9%) LPS-induced decreased spontaneous alteration in Y-maze test, as well as significantly restored LPS-elicited mice cognitive deficits through restoring performances such as escape distance in Morris water maze test. Moreover, sesamol prevented LPS-induced increases in Aß1-42 formation, levels of amyloid precursor protein, and neuronal ß-secretase 1 (BACE1) in the brain. Sesamol reduced LPS-induced glial over-activation by inhibiting MAPK and NFκB pathway as well as expressions of inflammatory mediators such as IL-1ß and TNFα. Furthermore, LPS-induced transcriptional factor NFκB DNA binding activity was also inhibited by sesamol as examined by the electrophoretic mobility shift assay and molecular modeling. CONCLUSION: These results indicated that sesamol mitigated LPS-induced amyloidogenesis and memory impairment via inhibiting NFκB signal pathway, suggesting that the compound might be plausible therapeutic intervention for neuroinflammation-related diseases such as AD.


Subject(s)
Antioxidants/administration & dosage , Benzodioxoles/administration & dosage , Dietary Supplements , Inflammation/drug therapy , Memory Disorders/prevention & control , NF-kappa B/metabolism , Phenols/administration & dosage , Amyloid Precursor Protein Secretases/genetics , Amyloid Precursor Protein Secretases/metabolism , Amyloid beta-Peptides/genetics , Amyloid beta-Peptides/metabolism , Animals , Aspartic Acid Endopeptidases/genetics , Aspartic Acid Endopeptidases/metabolism , Behavior, Animal/drug effects , Brain/drug effects , Brain/metabolism , Cells, Cultured , Inflammation/complications , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Lipopolysaccharides , Male , Memory Disorders/etiology , Mice , Mice, Inbred C57BL , Microglia/cytology , Microglia/drug effects , Microglia/metabolism , NF-kappa B/antagonists & inhibitors , NF-kappa B/genetics , Peptide Fragments/genetics , Peptide Fragments/metabolism , Protein Conformation , Signal Transduction , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
6.
Food Funct ; 7(9): 3902-9, 2016 Sep 14.
Article in English | MEDLINE | ID: mdl-27526679

ABSTRACT

Carrot pomace is an abundant, but underutilized, byproduct from the juice industry. In this study, the insoluble dietary fiber from carrot pomace was treated using an ultra-microgrinding process, and the resulting changes in its physicochemical properties and intestinal protective effect against heavy metal damage were examined. The SEM and fluorescence microscopy results showed that the grinding process could significantly decrease the particle size of carrot insoluble dietary fibre and increase its Brunauer-Emmett-Teller surface area from 0.374 to 1.835 m(2) g(-1). Correspondingly, the water-holding capacity, swelling capacity, and oil-holding capacity increased by 62.09%, 49.25% and 45.45%, respectively. The glucose-, nitrite-, and lead ion-adsorbing abilities also improved significantly compared with the raw samples. In addition, apoptosis assessment by AO/EB revealed that the ground fibre could effectively protect Caco-2 cells from lead ion damage. The MTT assay showed that carrot insoluble dietary fibre has no toxicity for Caco-2 cells at a concentration of 10.0 mg L(-1). The findings of this study highlighted the potential of the ultra-microgrinding process to produce a high added-value fibre ingredient from carrot residues.


Subject(s)
Daucus carota/chemistry , Enterocytes/metabolism , Plant Roots/chemistry , Prebiotics , Protective Agents/metabolism , Apoptosis/drug effects , Caco-2 Cells , Chelating Agents/adverse effects , Chelating Agents/chemistry , Chelating Agents/metabolism , Chemical Phenomena , China , Daucus carota/economics , Enterocytes/cytology , Enterocytes/drug effects , Food Handling , Food-Processing Industry/economics , Humans , Industrial Waste/analysis , Industrial Waste/economics , Lead/chemistry , Lead/metabolism , Lead/toxicity , Lead Poisoning/prevention & control , Microscopy, Electron, Scanning , Particle Size , Prebiotics/adverse effects , Prebiotics/analysis , Prebiotics/economics , Protective Agents/adverse effects , Protective Agents/chemistry , Protective Agents/economics , Solubility , Surface Properties
SELECTION OF CITATIONS
SEARCH DETAIL
...