当前位置: X-MOL 学术Food Chem. Toxicol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
CYPs-mediated drug-drug interactions on psoralidin, isobavachalcone, neobavaisoflavone and daidzein in rats liver microsomes.
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2019-12-21 , DOI: 10.1016/j.fct.2019.111027
Mengjun Shi 1 , Yiping Cui 1 , Cunyu Liu 2 , Changqin Li 3 , Zhenhua Liu 1 , Wen-Yi Kang 2
Affiliation  

The incubation system of CYP2E1 and CYP3A4 enzymes in rat liver microsomes was established to investigate the effects of psoralidin, isobavachalcone, neobavaisoflavone and daidzein from Fructus Psoraleae in vitro. The relevant metabolites were measured by the method of high performance liquid chromatography (HPLC), after probe substrates of 4-nitrophenol, testosterone and the drugs at different concentrations were added to the incubation systems. In addition, real-time RT-PCR was performed to determine the effect of psoralidin, neobavaisoflavone and daidzein on the mRNA expression of CYP3A4 in rat liver. The results suggested that psoralidin, isobavachalcone and neobavaisoflavone were Medium-intensity inhibitors of CYP2E1 with Ki values of 2.58, 1.28 and 19.07 μM, respectively, which could inhibit the increase of CYP2E1 and reduce diseases caused by lipid peroxidation. Isobavachalcone (Ki = 37.52 μM) showed a weak competitive inhibition on CYP3A4. Psoralidin and neobavaisoflavone showed obvious induction effects on CYP3A4 in the expression level of mRNA, which could accelerate the effects of drug metabolism and lead to the risk of inducing DDIs and serious adverse reactions. The results could be used for guideline of Fructus Psoraleae in clinic, which aimed to calculate the drug toxicity by studying the drug-drug interactions caused by the induction and inhibition of CYP450.

中文翻译:

在大鼠肝微粒体中,CYPs介导的补骨脂素,异巴伐康酮,新巴贝黄酮和黄豆苷元对药物的相互作用。

建立CYP2E1和CYP3A4酶在大鼠肝微粒体中的温育系统,以研究补骨脂中补骨脂素,异巴伐康酮,新黄酮和黄豆苷元的体外作用。在将4-硝基苯酚,睾丸酮和不同浓度药物的探针底物加入培养系统后,通过高效液相色谱法(HPLC)测量相关的代谢物。另外,进行实时RT-PCR以确定补骨脂素,新巴贝黄酮和大豆苷元对大鼠肝脏CYP3A4 mRNA表达的影响。结果表明,补骨脂素,异巴伐康酮和新巴贝黄酮是CYP2E1的中强度抑制剂,Ki值分别为2.58、1.28和19.07μM,可以抑制CYP2E1的升高,减少脂质过氧化引起的疾病。Isobavachalcone(Ki = 37.52μM)对CYP3A4表现出较弱的竞争抑制作用。补骨脂素和新巴贝黄酮对CYP3A4的mRNA表达水平有明显的诱导作用,可加速药物代谢作用,并有诱发DDI的危险和严重的不良反应。该研究结果可用于临床s骨的研究,旨在通过研究CYP450的诱导和抑制所引起的药物相互作用来计算药物毒性。这可能会加速药物代谢的作用,并导致诱发DDI和严重不良反应的风险。该研究结果可用于临床s骨的研究,旨在通过研究CYP450的诱导和抑制所引起的药物相互作用来计算药物毒性。这可能会加速药物代谢的作用,并导致诱发DDI和严重不良反应的风险。该结果可用于临床骨补骨科的指导,其目的是通过研究CYP450的诱导和抑制所引起的药物相互作用来计算药物毒性。
更新日期:2019-12-21
down
wechat
bug