Abstract
Purpose: To investigate the effect of farrerol on diabetic hepatopathy in a rat model of type 2 diabetes mellitus (T2DM).Methods: Adult male Wistar rats (n = 40) were randomly assigned to four groups of ten rats each: normal control, diabetic control, farrerol control and treatment groups. With the exception of normal control and farrerol control groups, the rats were fed high-fat diet (HFD) for four weeks, and thereafter injected streptozotocin (STZ) at a dose of 30 mg/kg body weight intraperitoneally (i.p.) for induction of T2DM. Rats in farrerol control and treatment groups received 50 mg/kg farrerol orally/day. Serum levels of triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and lowdensity lipoprotein cholesterol (LDL-C) were determined. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were assessed in liver homogenate while mRNA and protein expressions of glucose transporter 2 (GLUT2) were assayed in liver using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also determined using qRT-PCR.Results: Diabetes mellitus (DM) led to significant reductions in rat body weight and SOD activity, while increasing fasting blood glucose (FBG) and MDA levels (p < 0.05). However, treatment with farrerol significantly reversed the effect of DM on these parameters (p < 0.05). The mRNA expressions of TNF-α and IL-1β were significantly higher in diabetic control group than in normal control group, but were significantly reduced after farrerol treatment (p < 0.05). Treatment with farrerol also significantly reversed the effect of DM on rat lipid profile (p < 0.05). The expression of GLUT2 protein was significantly downregulated in the liver of diabetic control rats, when compared with normal control rats, but was significantly upregulated after treatment with farrerol (p < 0.05).Conclusion: The results of this study show that farrerol alleviates STZ-induced hyperglycemia and dyslipidemia via reduction in oxidative stress and inflammation, and upregulation of GLUT2 protein expression. Thus, farrerol has antidiabetic and hepatoprotective potentials for clinical use in humans.
 Keywords: Diabetes mellitus, Dyslipidemia, Farrerol, Hepatopathy, High-fat diet
Highlights
Diabetes mellitus (DM) is a heterogeneous group of syndromes characterized by elevation of fasting blood glucose (FBG) caused by a relative or absolute deficiency of insulin
Pre-clinical and epidemiological evidence indicate a clinical link between DM and liver diseases such as nonalcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), liver cirrhosis and metastatic hepatocellular carcinoma [2]
This study investigated the effect of farrerol on rat model of type 2 diabetes mellitus (T2DM)
Summary
Diabetes mellitus (DM) is a heterogeneous group of syndromes characterized by elevation of FBG caused by a relative or absolute deficiency of insulin. Nonalcoholic fatty liver is a common co-morbidity in approximately 70 % of patients with T2DM [3]. This explains the persistent occurrence of obesity and insulin resistance in diabetics. This study investigated the effect of farrerol on rat model of T2DM. The rats were exposed to 12 h light/12 h dark cycles and maintained at a temperature of 25 °C, and 50 % humidity in an aseptic environment They were acclimatized for seven days before commencement of the study, and had free access to standard feed and clean drinking water. The excised liver was homogenized using a Teflon homogenizer and the resultant homogenate was centrifuged at 3000 rpm for 10 min to obtain supernatant which was used for determination of SOD activity and MDA levels.
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