Evaluation of cinnamon (Cinnamomum Verum) effects on liver CYP450 2D1 activity and hepatic clearance in diabetic rats

Abstract

Objectives: The present study assessed the effects of cinnamon on the activity of the liver CYP2D1 enzyme and hepatic clearance in the rat model of type 1 and 2 diabetes mellitus. Methods: Male Wistar rats were randomly categorized into 8 groups. Fourteen days after induction of diabetes type 1 and 2, type 1 groups received cinnamon and insulin plus cinnamon and type 2 groups received cinnamon and metformin plus cinnamon daily for 14 days. On day 28, rats were subjected to liver perfusion by buffer containing dextromethorphan as the CYP2D1 enzyme activity probe. Perfused samples were analyzed by high-performance liquid chromatography (HPLC) with fluorescence (FL) detection to evaluate the CYP2D1 activity and hepatic clearance. Results: In the control group, enzyme activity and hepatic clearance changed from 0.0081 ± 0.00009 and 6.09 ± 0.2 mL/min to 0.0059 ± 0.0001 and 3.71 ± 0.07 mL/min in the untreated type 1 diabetic rats and to 0.0006 ± 0.0001 and 5.19 ± 0.02 mL/min in untreated type 2 ones. These pharmacokinetic (PK) parameters changed to 0.0069 ± 0.0005 and 6.27 ± 0.06 mL/min in treated type 1 and 0.0115 ± 0.0003 and 5.79 ± 0.11 mL/min in the treated type 2 rats with only cinnamon administration. Treatment with cinnamon plus insulin or metformin modulated these PK parameters to 0.0039 ± 0.00006 and 4.88 ± 0.13 mL/min in type 1 and 0.0092 ± 0.0005 and 6.13 ± 0.01 mL/min in type 2 diabetic rats. Conclusions: Cinnamon can act as an effective complementary medicine in order to normalize the metabolism and clearance processes in diabetes mellitus.