ABSTRACT
AIM: Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea. In this study, we investigated the effects of EGCG on insulin resistance and insulin clearance in non-alcoholic fatty liver disease (NAFLD) mice. METHODS: Mice were fed on a high-fat diet for 24 weeks. During the last 4 weeks, the mice were injected with EGCG (10, 20 and 40 mg·kg(-1)·d(-1), ip). Glucose tolerance, insulin tolerance and insulin clearance were assessed. After the mice were euthanized, blood samples and tissue specimens were collected. Glucose-stimulated insulin secretion was examined in isolated pancreatic islets. The progression of NAFLD was evaluated histologically and by measuring lipid contents. Insulin-degrading enzyme (IDE) protein expression and enzyme activity were detected using Western blot and immunocapture activity assays, respectively. RESULTS: The high-fat diet significantly increased the body weight and induced grade 2 or 3 liver fatty degeneration (steatosis, lobular inflammation and ballooning) accompanied by severe hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in the model mice. Administration of EGCG dose-dependently ameliorated the hepatic morphology and function, reduced the body weight, and alleviated hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in NAFLD mice. Furthermore, EGCG dose-dependently enhanced insulin clearance and upregulated IDE protein expression and enzyme activity in the liver of NAFLD mice. CONCLUSION: EGCG dose-dependently improves insulin resistance in NAFLD mice not only by reducing body weight but also through enhancing the insulin clearance by hepatic IDE. The results suggest that IDE be a potential drug target for the treatment of NAFLD.
Subject(s)
Camellia sinensis , Catechin/analogs & derivatives , Hypoglycemic Agents/pharmacology , Insulin Resistance , Liver/drug effects , Non-alcoholic Fatty Liver Disease/drug therapy , Animals , Biomarkers/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , Catechin/pharmacology , Diet, High-Fat , Disease Models, Animal , Dose-Response Relationship, Drug , Insulin/blood , Insulysin/metabolism , Liver/metabolism , Liver/pathology , Male , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/pathology , Phytotherapy , Plants, Medicinal , Time FactorsABSTRACT
OBJECTIVE: To investigate the effect of Resveratrol on Hydrogen peroxide-treated human umbilical vein endothelial cells (HUVEC). METHODS: Oxidative stress in HUVEC was induced by hydrogen peroxide (H2O2). The cells were divided in to 5 groups: A. Control group; B. H2O2 group; C. Res + H2O2 group; D. Res + H2O2 + LY294002 group; E. H2O2 + LY294002 group. The cell viability were measured by cck-8 assay; Malondialdehyde (MDA) and Superoxide dismutase (SOD) were determined by using commercially available kits; Reactive oxygen species (ROS)were detect by flow cytometer; the expression of Nuclear factor-E2-related factor(Nrf2), Protein kinase B(Akt), Mammalian target of rapamycin (mTOR) were determined by Western blot. RESULTS: Compared with control, resveratrol increased the cells viability (36.14 ± 2.20) to (72.05 ± 2.46) (P = 0.004), decreased MDA formation (299.38 ± 12.42) to (159.17 ± 7.30)(P = 0.006), elevated SOD activity(35.61 ± 3.26) to (81.37 ± 4.55) (P = 0.007), inhibited ROS production (177.86 ± 8.98) to (133.96 ± 4.17) (P = 0.003). These changes were accompany with the activation of p-Nrf2 (198.57 ± 6.89) to (371.10 ± 8.41) (P = 0.005), p-Akt (102.93 ± 3.29) to (221.62 ± 6.51) (P = 0.004), p-mTOR (93.26 ± 4.12) to (172.14 ± 5.74) (P = 0.008). However these protective effect of resveratrol were abolished by LY294002. CONCLUSION: Resvertrol could protects HUVEC cells from H2O2-induced oxidative stress, in which the PI3K-Akt-mTOR pathway may be involved.
Subject(s)
Human Umbilical Vein Endothelial Cells/drug effects , Oxidative Stress/drug effects , Stilbenes/pharmacology , Cells, Cultured , Human Umbilical Vein Endothelial Cells/cytology , Humans , Hydrogen Peroxide/metabolism , Reactive Oxygen Species/metabolism , ResveratrolABSTRACT
The anti-inflammatory properties of soyasaponins (especially soyasaponins with different chemical structures) have scarcely been investigated. We investigated the inhibitory effects of five structural types of soyasaponins (soyasaponin A(1), A(2), I and soyasapogenol A, B) on the induction of nitric oxide (NO) and inducible NO synthase (iNOS) in murine RAW 264.7 cells activated with lipopolysaccharide (LPS). Soyasaponin A(1), A(2) and I (25-200 µg/mL) dose-dependently inhibited the production of NO and tumor necrosis factor α (TNF-α) in LPS-activated macrophages, whereas soyasapogenol A and B did not. Furthermore, soyasaponin A(1), A(2) and I suppressed the iNOS enzyme activity and down-regulated the iNOS mRNA expression both in a dose-dependent manner. The reporter gene assay revealed that soyasaponin A(1), A(2) and I decreased LPS-induced nuclear factor kappa B (NF-κB) activity. Soyasaponin A(1), A(2) and I exhibit anti-inflammatory properties by suppressing NO production in LPS-stimulated RAW 264.7 cells through attenuation of NF-κB-mediated iNOS expression. It is proposed that the sugar chains present in the structures of soyasaponins are important for their anti-inflammatory activities. These results have important implication for using selected soyasaponins towards the development of effective chemopreventive and anti-inflammatory agents.
