Faculty of Medicine, Jinhua Polytechnic, Zhejiang, People's Republic of China.
Drug Des Devel Ther. 2020 Jan 29;14:429-434. doi: 10.2147/DDDT.S236221. eCollection 2020.
Calycosin (CAL), a type of O-methylated isoflavone extracted from the herb (AM), is a bioactive chemical with antioxidative, antiphlogistic and antineoplastic activities commonly used in traditional alternative Chinese medicine. AM has been shown to confer health benefits as an adjuvant in the treatment of a variety of diseases.
The main objective of this study was to determine whether CAL influences the cytochrome P450 (CYP450) system involved in drug metabolism.
Midazolam, tolbutamide, omeprazole, metoprolol and phenacetin were selected as probe drugs. Rats were randomly divided into three groups, specifically, 5% Carboxymethyl cellulose (CMC) for 8 days (Control), 5% CMC for 7 days + CAL for 1 day (single CAL) and CAL for 8 days (conc CAL), and metabolism of the five probe drugs evaluated using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
No significant differences were observed for omeprazole and midazolam, compared to the control group. and t values of only one probe drug, phenacetin, in the conc CAL group were significantly different from those of the control group ( h: 0.50±0.00 vs 0.23±0.15; control vs conc CAL). of tolbutamide was decreased about two-fold in the conc CAL treatment group (conc vs control: 219.48 vs 429.56, <0.001).
Calycosin inhibits the catalytic activities of CYP1A2, CYP2D6 and CYP2C9. Accordingly, we recommend caution, particularly when combining CAL as a modality therapy with drugs metabolized by CYP1A2, CYP2D6 and CYP2C9, to reduce the potential risks of drug accumulation or ineffective treatment.
毛蕊异黄酮（CAL）是从草药（AM）中提取的一种 O-甲基化异黄酮，是一种具有抗氧化、抗炎和抗肿瘤活性的生物活性化学物质，常用于传统替代中医。AM 已被证明作为辅助治疗多种疾病具有健康益处。
本研究的主要目的是确定 CAL 是否会影响参与药物代谢的细胞色素 P450（CYP450）系统。
选择咪达唑仑、甲苯磺丁脲、奥美拉唑、美托洛尔和非那西汀作为探针药物。将大鼠随机分为三组，分别为 5%羧甲基纤维素（CMC）8 天（对照组）、5%CMC 7 天+CAL1 天（单次 CAL）和 CAL8 天（高浓度 CAL），并使用超高效液相色谱-串联质谱法（UPLC-MS/MS）评估 5 种探针药物的代谢情况。
与对照组相比，奥美拉唑和咪达唑仑无显著差异。仅在高浓度 CAL 组中，一种探针药物非那西汀的 t 值与对照组有显著差异（h：0.50±0.00 对 0.23±0.15；对照组对高浓度 CAL）。甲苯磺丁脲在高浓度 CAL 治疗组中降低了约两倍（高浓度对对照组：219.48 对 429.56，<0.001）。
毛蕊异黄酮抑制 CYP1A2、CYP2D6 和 CYP2C9 的催化活性。因此，我们建议谨慎，特别是当将 CAL 作为一种与 CYP1A2、CYP2D6 和 CYP2C9 代谢的药物联合使用的模式治疗时，以降低药物蓄积或无效治疗的潜在风险。
