Changes in CYP2D enzyme activity following induction of type 2 diabetes, and administration of cinnamon and metformin: an experimental animal study

Abstract

1. Alterations in the activity of hepatic cytochrome P-450 isoenzymes result in changes in the pharmacokinetic behavior of drugs. This study was designed to explore the impact of type II diabetes, metformin and cinnamon on the activity of CYP2D isoenzyme. 2. Streptozotocin-nicotinamide-induced diabetic and normal rats were gavaged by cinnamon and/or metformin for 14 days. Using isolated perfusion of rat livers, the metabolic activity of CYP2D in the study groups was evaluated based on the oxidative biotransformation of tramadol hydrochloride. 3. The metabolic ratios of O-desmethyltramadol, the product of CYP2D-mediated metabolism of tramadol, in normal and diabetic control rats were found to be 0.33 ± 0.12 and 0.29 ± 0.07, respectively. Cinnamon significantly reduced the mentioned ratio in both normal and diabetic rats (0.13 ± 0.05 and 0.15 ± 0.04) and metformin increased the reduced activity in diabetic rats (0.37 ± 0.09 versus 0.29 ± 0.07). 4. In conclusion, it is evident that this study has shown the significant inhibitory effect of cinnamon on CYP2D. This finding suggests that it should be taken into consideration the possible metabolism-related pharmacokinetic drug-cinnamon interactions. 5. Additionally, type 2 diabetes condition reduced the enzyme activity and metformin consumption reversed this reduction; however, the significance of the latest is not clear.

Effects of Cinnamon Powder on Glucose Metabolism in Diabetic Mice and the Molecular Mechanisms

“…A previous study suggested that the effective hypoglycemic dose for CP in mice is approximately 300 mg/kg b.w. [40]. The effective dosage of cinnamon can vary depending on factors such as the variety of cinnamon, which can influence the bioactive contents of the plant material and consequently affect its bioactivity [6].…”

Effects of cinnamon supplementation on expression of systemic inflammation factors, NF-kB and Sirtuin-1 (SIRT1) in type 2 diabetes: a randomized, double blind, and controlled clinical trial

“…Data were represented as mean ± standard deviation (SD) and *P < 0.05 was considered as statistically significant. hs-CRP, high-sensitive C-Reactive Protein; TNF-α, Tumor Necrosis Factor-alpha; IL-6, Interleukine-6; NF-kB, Nuclear factor-Kappa B; SIRT1, Sirtuin-1 elucidated in another study by Taheri et al that the effectiveness of metformin increases in the high dose of cinnamon, but significant effect was not seen in low dose [38]. Although we used 3000 mg/day cinnamon on human in our study, it was not observed any pharmacodynamic effects.…”

Systematic analysis and identification of the absorption and metabolic components of Zengye decoction in type 2 diabetic rats by HPLC-ESI-Q-TOF–MS/MS

“…A previous study found that the plasma concentrations of catalpol and harpagide in diabetes-model rats were increased compared with normal rats, and that the clearance rate was slower [11]. Diabetes also changes the experesion of cytochrome P450 enzymes, including CYP3A4, CYP2E1, CYP2C9, and CYP2D4 participate in phase I drug metabolism [33][34][35]. Catalpol has been shown to effect the activity of CYP3A4, CYP2E1 and CYP2C9 that resulted in pharmacokinetic interactions of coadministered drugs [36].…”