Tartary buckwheat flavonoids ameliorate high fructose-induced insulin resistance and oxidative stress associated with the insulin signaling and Nrf2/HO-1 pathways in mice

Abstract

The present study was conducted to explore the effects of a purified tartary buckwheat flavonoid fraction (TBF) on insulin resistance and hepatic oxidative stress in mice fed high fructose in drinking water (20%) for 8 weeks. The results indicated that continuous administration of TBF dose-dependently improved the insulin sensitivity and glucose intolerance in high fructose-fed mice. TBF treatment also reversed the reduced level of insulin action on the phosphorylation of insulin receptor substrate-1 (IRS-1), protein kinase B (Akt) and phosphatidylinositol 3-kinase (PI3K), as well as the translocation of glucose transporter type 4 (GLUT4) in the insulin-resistant liver. Furthermore, TBF was found to exert high antioxidant capacity as it acts as a shield against oxidative stress induced by high fructose by restoring the antioxidant status, and modulating nuclear factor E2 related factor 2 (Nrf2) translocation to the nucleus with subsequently up-regulated antioxidative enzyme protein expression. Histopathological examinations revealed that impaired pancreatic/hepatic tissues were effectively restored in high fructose-fed mice following TBF treatment. Our results show that TBF intake is effective in preventing the conversion of high fructose-induced insulin resistance and hepatic oxidative stress in mice by improving the insulin signaling molecules and the Nrf2 signal pathway in the liver.

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“…The results in Fig.4 a, b showed the elevation of hepatic oxidant activities (MDA) and the reduction of GSH levels (P < 0.0001) in HFD groups caused by increasing the fructose catabolism. These results conformed to results of "Hu et al [50]" who observed that chronic fructose consumption was resulting in a significant elevation in hepatic peroxidation of lipid (MDA) and a significant reduction in antioxidant enzyme activities (GSH) of the liver in high fructose-fed mice.…”

Rice bran oil ameliorates hepatic insulin resistance by improving insulin signaling in fructose fed-rats

“…Moreover, high-fructose levels down-regulates both GLUT4 and GLUT5 genes expression in the liver. These results agree with previous studies which reported impaired insulin action and a decrease in GLUT4 expression in insulin resistance [27,35]. The current results established that exposure to high concentrations of fructose induces insulin resistance like conditions, including inhibition of the Akt/PI3K pathway.…”

“…Rats fed high-fructose diet showed elevated levels of serum ALT and AST, the specific markers of hepatocellular injury [25,26]. Previous studies agree with the current results only for serum ALT in HFD1 and HFD2 [25][26][27]. These elevations were significantly reduced in groups fed HFD containing RBO, compared to their respective control rats.…”

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“…8 As the core component of the biological activity of some plant leaves, plant flavonoids have a strong antioxidative effect, and they also exert the functions of enhancing immunity, preventing heart and brain blood diseases, and reducing blood lipids and cholesterol, which play an important role in human fat metabolism. [9][10][11] Esophageal cancer is a common digestive tract tumor, and about 300,000 people die of esophageal cancer every year in the world. 12 The occurrence of esophageal cancer may be related to many factors, such as heredity, environment, and lifestyle, but the exact pathogenesis has not been clarified.…”

“…8 As the core component of the biological activity of some plant leaves, plant flavonoids have a strong anti-oxidative effect, and they also exert the functions of enhancing immunity, preventing heart and brain blood diseases, and reducing blood lipids and cholesterol, which play an important role in human fat metabolism. 9 – 11…”