| Summary: | 博士 === 國立嘉義大學 === 食品科學系研究所 === 105 === Methylglyoxal (MG) is a highly reactive dicarbonyl compound. The glycation reaction of MG with protein, lipid, and DNA lead to oxidative stress, diabetes mellitus, microvascular complications, atherosclerosis, hypertension, and aging. Tartary buckwheat is rich in rutin and quercetin, and has been shown to possess antiglycative, hepatoprotective and antidiabetic ability. This research investigated the effect of ethanol extracts from tartary buckwheat (EEB), rutin and quercetin on insulin resistance, nonalcoholic fatty liver disease (NAFLD), and accumulation and metabolism of MG in high fructose/MG (HF/MG) diet rats. Firstly, the protective effect of EEB on insulin resistance through receptor for advanced glycation end products (RAGE) pathway was discussed. EEB alleviated HF/MG diet induced insulin resistance by improved glucose tolerance, decreased HOMA-IR, increased hepatic glucose uptake, and reversed hepatic glucose transporter-2 (GLUT2) expression. EEB also inhibited production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and expression of nuclear factor-kappa B (NF-κB) and RAGE in liver of HF/MG diet rats. The results showed that EEB stimulated glucose uptake through enhanced GLUT2 expression, and decreased inflammatory response by inhibiting RAGE-NF-κB pathway, it suggested that EEB enhanced insulin sensitivity by improving glucose metabolism disorders. Furthermore, due to high correlation between insulin resistance and NAFLD, the effect of EEB on HG/MH diet induced NAFLD was assessed. HF/MG diet resulted in functional impairment, lipid accumulation, adipogenic change, and oxidative stress in rat liver. The administration of EEB reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL), malonaldehyde (MDA), and reactive oxygen species (ROS) levels in serum and liver, which showed hepatoprotection. In addition, EEB also increased the concentration of serum leptin and adiponectin, and reversed the expression of peroxisome proliferator-activated receptor-α (PPARα) and PPARγ. Results indicated that EEB presented protective effect of fat-related liver damage by increasing leptin and adiponectin concentration, and showing the function of dual PPARα/γ agonists, and moreover decreased the development of NAFLD. Combined the results of two chapters, it exhibited insulin resistance and NAFLD in HF/MG diet rats. We examined further on the protection effect of EEB against MG accumulation by regulation of glyoxalase (GLO), and evaluated the effect of relative complications. Higher levels of MG in serum and hepatic were found in HF/MG diet rats, but the MG accumulation was decreased when treating together with EEB, moreover increased the D-lactate contents. EEB also inhibited the decline of GLO-1, GLO-2 and glutathione peroxidase (GPx) activity and the depletion of glutathione (GSH) which induced by HF/MG diet. In MG related complications, there had no effect on renal and vascular complications in rats which gave HF/MG diet for 8 weeks. The results of this chapter indicated that EEB alleviates MG accumulation through GLO system. Moreover, rutin and quercetin, the major activity compounds of tartary buckwheat, also improved insulin resistance, decreased inflammatory response, and assuaged NAFLD. In summary, EEB not only possess lowering capability in MG accumulation and alleviating RAGE-related inflammatory by enhancing GLO activity, also increase the concentration of leptin and adiponectin and the protein expressions of PPARα and PPARγ. Therefore, EEB exist potential therapeutic use for the treatment of insulin resistance and NAFLD, and rutin and quercetin played important roles in this protective effect.
|
|---|
