Key Points
Currently, obesity and type 2 diabetes mellitus (T2DM) are considered as the foremost prevalent metabolic disorders in both developed and developing countries. Chronic consumption of high-fat diet has been shown to induce numerous changes and deposition of fat in the liver, which is characterised by insulin resistance and T2DM. Herbacetin is a natural flavonoid compound found in flaxseed and other plants. Herbacetin is known to have strong antioxidant activity and antitumor properties in the breast, colon, and skin. This study assessed whether herbacetin can increase insulin sensitivity by improving lipid metabolism. In this study, feeding mice with high-fat diet significantly increased the body weight, food intake, blood glucose level, insulin level, HOMAIR, and other biochemical parameters. Intragastric administration of herbacetin for 5 weeks resulted in decreased body weight and food intake when compared to OIR control mice, which could be due to enhanced insulin sensitivity. After the administration of herbacetin, plasma glucose and insulin levels and index of HOMA decreased in OIR mice when compared to normal control mice. These results indicate that the anti-hyperglycaemic activity of herbacetin is due to an improvement in insulin sensitivity and lipid lowering activity. In the present study, herbacetin reduced the elevated glycosylated haemoglobin in OIR mice, confirming that herbacetin prevents haemoglobin glycation through its anti-hyperglycaemic activity. In the current study, the activities of serum AST and ALT increased significantly in HF-induced group, which can be due to the leakage of these enzymes from the cytosol into the blood stream. The administration of herbacetin along with a high fat diet restores the activities of these enzymes to near normal mice values, which could be due to an improvement in insulin sensitivity and lipid lowering activity. The investigators suggested that herbacetin in flaxseed has anti-hyperglycaemic and antihyperlipidemic action against HFD induced T2DM, which might be due to its effect in controlling lipid metabolizing and lipid-regulating enzymes activities.
ABSTRACT
Healthy plants and their constituents have been considered as a safe remedy for the treatment of obesity and obesity associated diseases. Herbacetin is a dietary flavonoid that has been explored for many pharmacological activities; but, the anti-hyperglycaemic and anti-hyperlipidemic properties of herbacetin have not yet been explored. The present study was performed to evaluate the ameliorative effect of herbacetin on high-fat diet-induced hyperglycaemia and hyperlipidemia in 57BL/6 J mice. Obesity associated insulin resistance was induced by continuously feeding the mice with high-fat diet for 10 weeks. Afterwards, mice were subjected to intragastric administration of herbacetin (different doses) daily along with high-fat diet for the next 5 weeks. At the end of 106th day, changes in body weight, blood glucose, insulin, HOMA-IR, and lipids profiles and lipid-regulating enzymes were evaluated. Herbacetin significantly reduced the body weight, plasma glucose, plasma insulin, and HOMA-IR activity in obesity associated insulin resistant mice (OIR). In addition, herbacetin administration significantly reduced the plasma and hepatic total cholesterol, triglycerides, and free fatty acids in OIR mice. Moreover, herbacetin significantly improved the altered hepatic lipid metabolizing and lipid-regulating enzymes such as SREBP-1c, and 2, fatty acid synthase (FAS), fatty acid β-oxidation (β-oxidation), malic enzyme, glucose 6-phosphate dehydrogenase (G6PD), and carnitine palmitoyltransferase (CPT) when compared to OIR control mice. Histopathological examination clearly showed that herbacetin decreases lipid droplets in the liver tissue. Thus, observed results strongly indicate that herbacetin provides remarkable protection against the harmful effects of chronic high-fat diet consumption because of its anti-hyperglycaemic and anti-hyperlipidemic properties through the regulation of hepatic lipid metabolizing and lipid-regulating enzymes.
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