Jearapong Nattharat, Chatuphonprasert Waranya, Jarukamjorn Kanokwan
Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology (PANPB), Khon Kaen University, Khon Kaen 40002, Thailand; Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology (PANPB), Khon Kaen University, Khon Kaen 40002, Thailand; Faculty of Medicine, Mahasarakham University, Mahasarakham 44000, Thailand.
Chem Biol Interact. 2015 Sep 5;239:67-75. doi: 10.1016/j.cbi.2015.06.022. Epub 2015 Jun 20.
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.
细胞色素P450（CYP）是肝脏单加氧酶的一个超家族，催化内源性化合物和外源性物质的生物转化。CYP的改变与代谢性疾病以及持续食用高能量水平的饮食有关。四氢姜黄素（THC）在糖尿病和血脂异常等代谢综合征中显示出有益作用。本研究旨在探讨THC和维生素E（vitE）对高脂高糖饮食喂养的小鼠肝脏中CYPs表达谱的影响。除了随意获取市售常规饮食外，成年雄性ICR小鼠的高脂高糖饮食（HFD）组给予高脂高糖饮食，即每天灌胃氢化大豆油（1mL/天）并在饮用水中添加20%果糖，持续8周。在诱导期，将小鼠亚组（n = 5）每天经胃内给予THC（100或2百毫克/千克/天）或vitE（100毫克/千克/天）。使用实时PCR定量CYP mRNA和蛋白质的表达，并使用免疫印迹法定量这些蛋白质的水平。连续8周食用高脂高糖显著增加了Cyp1a1、Cyp1a2、Cyp1b1、Cyp2c29和Cyp3a11的表达，而THC最终使这些CYPs谱恢复正常。在对照小鼠中，大多数研究的CYPs不受THC影响，但Cyp1a1、Cyp2b9和Cyp3a11蛋白有所升高。这些发现为THC对饮食诱导的代谢功能障碍的影响提供了额外的重要信息。然而，将THC用作替代补充剂时的药物相互作用令人担忧，特别是在包括作为Cyp1a1、Cyp2b9和Cyp3a11底物的药物的组合中。
