Effect of tetrahydrocurcumin on the profiles of drug-metabolizing enzymes induced by a high fat and high fructose diet in mice

Abstract

Cytochrome P450 (CYP), a superfamily of hepatic monooxygenase enzymes, catalyzes biotransformation of endogenous compounds and xenobiotics. Modification of CYPs associated with metabolic diseases and continuous consumption of diet with excessive energy levels. Tetrahydrocurcumin (THC) exhibited beneficial effects in metabolic syndromes such as diabetic mellitus and dyslipidemia. The present study aimed to investigate the effects of THC and vitamin E (vitE) on the expression profiles of CYPs in the livers of mice fed with the high fat and high fructose diet. In addition to ad libitum access to commercial regular diet, the high fat and high fructose diet (HFD) group of adult male ICR mice was administered a HFD, which consisted of intragastric administration of hydrogenated soybean oil (1mL/day) and the addition of 20% fructose to the drinking water for 8weeks. During the induction period, subgroups of mice (n=5) were daily intragastrically administered with THC (100 or 200mg/kg/day) or vitE (100mg/kg/day). The expressions of CYP mRNA and protein were quantified using real-time PCR and the levels of these proteins were quantified using immunoblotting. Continuous consuming of high fat and high fructose for 8weeks significantly increased the expressions of Cyp1a1, Cyp1a2, Cyp1b1, Cyp2c29, and Cyp3a11 while THC ultimately normalized these CYPs profiles. In the control mice, most of the investigated CYPs was unchanged by THC, with the exception that the Cyp1a1, Cyp2b9, and Cyp3a11 proteins were elevated. These findings provided additional important information on the effects of THC on diet induced-metabolic dysfunctions. However, drug interactions due to the use of THC as an alternative supplement are of concern, particularly in the combinations that include a drug that is a substrate of Cyp1a1, Cyp2b9, and Cyp3a11.

Keywords: Cytochrome P450s; High fat and high fructose diet; Tetrahydrocurcumin.