The therapeutic effects of berberine plus sitagliptin in a rat model of fatty liver disease

Objective(s): Fatty liver disease (FLD) is a disorder related to accumulation of excess fat within the hepatocytes. In this study, the effects of Berberine, a natural compound, and Sitagliptin as a DPP-۴ inhibitor, were observed in a rat model of FLD.Materials and Methods: Forty male rats were divided into five groups (n=۶) including the control group (normal food and water), high-fat group (high-fat diet (HF) for ۶ weeks), Berberine group (HF with oral administration of Berberine at ۱۵۰ mg/kg for ۶ weeks), Sitagliptin group (HF with oral administration of Sitagliptin at ۱۰ mg/kg for ۶ weeks), and Berberine/ Sitagliptin group (HF diet within combination with oral administration of Berberine ۷۵ mg/kg and Sitagliptin ۵ mg/kg for ۶ weeks). Animals were examined for weight gain, serum and hepatic biochemical parameters, tissue histology, expression of glucose transporter type ۴ (GLUT۴) mRNA, and protein expression of Adiponectin receptor۲ (AdipoR۲) and extracellular signal-regulated kinase (ERK) and phoERK.Results: The results showed that ALT, AST, lipid profile, insulin, glucose, MDA, and TNF-α were significantly improved in high-fat rats treated with Berberine/ Sitagliptin compared with HF and Sitagliptin, and Berberine alone groups. SOD and adiponectin levels in Berberine/ Sitagliptin group were also significantly increased compared with the other groups. Immunoblot analysis showed that the expression of pho-ERK/ERK was significantly decreased and expression of AdipoR۲ significantly increased in the Berberine/ Sitagliptin group compared with other groups.Conclusion: Co-administration of Berberine and Sitagliptin is an effective therapeutic regimen for conditions associated with hyperlipidemia.

Keywords:

Adiponectin receptor۲ DDP , ۴ Glucose ttransporter type ۴ Natural compound Non , alcoholic fatty liver disease Pho , ERK/ERK