Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China.
National Clinical Drug Monitoring Center, Department of Pharmacy, Hebei Province General Center, Shijiazhuang 050051, China.
Molecules. 2019 Mar 25;24(6):1171. doi: 10.3390/molecules24061171.
Galangin is a marker compound of honey and Hance that exhibits great potential for anti-microbial, anti-diabetic, anti-obesity, anti-tumour and anti-inflammatory applications. Galangin is frequently consumed in combination with common clinical drugs. Here, we evaluated the effects of galangin on cytochrome P450 (CYP)-mediated metabolism, using two different approaches, to predict drug⁻drug interactions. Male Sprague Dawley rats were administered galangin daily for 8 weeks. A "cocktail-probes" approach was employed to evaluate the activities of different CYP450 enzymes. Blood samples of seven probe drugs were analysed using liquid chromatography-tandem mass spectrometry in positive and negative electrospray-ionisation modes. Pharmacokinetic parameters were calculated to identify statistical differences. CYP mRNA-expression levels were investigated in real-time quantitative polymerase chain reaction experiments. The galangin-treated group showed significantly decreased AUC and C values for CYP1A2, and CYP2B3. The galangin-treated group showed significantly increased AUC and C values for CYP2C13 and CYP3A1. No significant influences were observed in the pharmacokinetic profiles of CYP2C11, CYP2D4 and CYP2E1. The mRNA-expression results were consistent with the pharmacokinetic results. Thus, CYP450 enzyme activities may be altered by long-term galangin administration, suggesting galangin to be a promising candidate molecule for enhancing oral drug bioavailability and chemoprevention and reversing multidrug resistance.
姜黄素是蜂蜜和 Hance 的标志物化合物，具有很强的抗微生物、抗糖尿病、抗肥胖、抗肿瘤和抗炎应用潜力。姜黄素经常与常用的临床药物联合使用。在这里，我们使用两种不同的方法评估了姜黄素对细胞色素 P450（CYP）介导的代谢的影响，以预测药物相互作用。雄性 Sprague Dawley 大鼠每天给予姜黄素 8 周。采用“鸡尾酒探针”方法评估不同 CYP450 酶的活性。使用液相色谱-串联质谱法在正、负离子喷雾电离模式下分析七种探针药物的血样。计算药代动力学参数以确定统计学差异。通过实时定量聚合酶链反应实验研究 CYP mRNA 表达水平。姜黄素处理组 CYP1A2 和 CYP2B3 的 AUC 和 C 值显著降低。姜黄素处理组 CYP2C13 和 CYP3A1 的 AUC 和 C 值显著升高。CYP2C11、CYP2D4 和 CYP2E1 的药代动力学特征没有明显影响。mRNA 表达结果与药代动力学结果一致。因此，长期姜黄素给药可能会改变 CYP450 酶活性，表明姜黄素是增强口服药物生物利用度、化学预防和逆转多药耐药性的有前途的候选分子。
