和厚朴酚对 2 型糖尿病大鼠 CYP450 活性和转运体 mRNA 表达的影响。
Effects of Honokiol on CYP450 Activity and Transporter mRNA Expression in Type 2 Diabetic Rats.
机构信息
Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine; Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, Hubei University, Wuhan 430062, China.
出版信息
Int J Mol Sci. 2018 Mar 12;19(3):815. doi: 10.3390/ijms19030815.
This study was aimed to clarify the effect of honokiol (Hon) on the activity of Cytochrome P450 (CYP450) enzymes, and the level of mRNA expression of liver and kidney transporters in type 2 diabetic rats induced by high-fat diet and strepotozotocin. Rats were randomly divided into normal control (NC) group, diabetic control (DC) group and Hon groups ( = 6). The activities of hepatic CYP1A2, CYP2E1, CYP2C, CYP2B, CYP3A and CYP4A, and the mRNA expression levels of hepatic and renal transporters, were determined. Compared to the NC group, the activities of CYP1A2, CYP2E1, CYP4A and CYP2C in DC group were increased by 2.36-, 2.10-, 2.55- and 1.86-fold, respectively. The mRNA expression levels of hepatic Oat2, Oatp2b1 and Oatp1a5, and renal Oct1, Octn2, Oatp2b1 and Oatp1a5, were significantly down-regulated, while the mRNA expression levels of hepatic Octn2, Oatp3a1, Oatp1a1 and Mdr2, and renal Oat2, Mrp4 and Bcrp, were significantly upregulated. Compared to the DC group, Hon treatment significantly inhibited the activity of hepatic CYP2E1, CYP4A, 3A and CYP1A2 by 45.6%, 29.2%, 22.7% and 20.7% in Hon high dose group, respectively. Moreover, Hon treatment significantly inhibited the mRNA expression levels of renal Bcrp and Mrp4 by 2.63-fold and 1.54-fold, while significantly upregulated the mRNA expression levels of hepatic Oat2 and Oatp2b1 by 1.52-fold and 1.54-fold in Hon high dose group, respectively. The results suggested that under the diabetes condition, the changes of CYP450 activity and transporter expression inevitably interfere the normal transport, metabolism and efficacy of drugs. The present work firstly reported that Hon treatment ameliorated the abnormal change of hepatic CYP activity (including CYP2E1, CYP4A and CYP1A2) and the transporter mRNA expression (including hepatic Oat2 and Oatp2b1, renal Bcrp and Mrp4) in type 2 diabetic rats induced by high-fat diet and strepotozotocin, which are associated with the occurrence and development of diabetes.
本研究旨在阐明霍诺醇（Hon）对高脂肪饮食和链脲佐菌素诱导的 2 型糖尿病大鼠细胞色素 P450（CYP450）酶活性和肝脏及肾脏转运体 mRNA 表达水平的影响。大鼠随机分为正常对照组（NC）、糖尿病对照组（DC）和 Hon 组（n=6）。测定肝 CYP1A2、CYP2E1、CYP2C、CYP2B、CYP3A 和 CYP4A 的活性，以及肝和肾转运体的 mRNA 表达水平。与 NC 组相比，DC 组 CYP1A2、CYP2E1、CYP4A 和 CYP2C 的活性分别增加了 2.36、2.10、2.55 和 1.86 倍。肝 Oat2、Oatp2b1 和 Oatp1a5 及肾 Oct1、Octn2、Oatp2b1 和 Oatp1a5 的 mRNA 表达水平显著下调，而肝 Octn2、Oatp3a1、Oatp1a1 和 Mdr2 及肾 Oat2、Mrp4 和 Bcrp 的 mRNA 表达水平显著上调。与 DC 组相比，Hon 高剂量组可分别显著抑制肝 CYP2E1、CYP4A、CYP3A 和 CYP1A2 的活性，抑制率分别为 45.6%、29.2%、22.7%和 20.7%。此外，Hon 高剂量组可显著抑制肾 Bcrp 和 Mrp4 的 mRNA 表达水平，抑制率分别为 2.63 倍和 1.54 倍，同时显著上调肝 Oat2 和 Oatp2b1 的 mRNA 表达水平，上调率分别为 1.52 倍和 1.54 倍。结果表明，在糖尿病状态下，CYP450 活性和转运体表达的变化必然会干扰药物的正常转运、代谢和疗效。本研究首次报道，Hon 治疗可改善高脂肪饮食和链脲佐菌素诱导的 2 型糖尿病大鼠 CYP 活性（包括 CYP2E1、CYP4A 和 CYP1A2）和转运体 mRNA 表达（包括肝 Oat2 和 Oatp2b1、肾 Bcrp 和 Mrp4）的异常变化，这些变化与糖尿病的发生发展有关。
Zotero 插件