Chen Jun-Jun, Zhang Jing-Xian, Zhang Xiang-Qi, Qi Mei-Juan, Shi Mei-Zhi, Yang Jiao, Zhang Ke-Zhi, Guo Cheng, Han Yong-Long
Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai 200233, China.
College of Food Science and Technology, Shanghai Ocean University, 999 Hucheng Huan Road, Shanghai 201306, China.
Toxicol Appl Pharmacol. 2017 Nov 1;334:1-7. doi: 10.1016/j.taap.2017.08.020. Epub 2017 Sep 1.
Diosmetin (3', 5, 7-trihydroxy-4'-methoxyflavone), a natural flavonoid from traditional Chinese herbs, has been used in various medicinal products because of its anticancer, antimicrobial, antioxidant, estrogenic and anti-inflammatory activity. However, flavonoids could affect the metabolic enzymes and cause drug-drug interactions (DDI), reducing the efficacy of co-administered drugs and potentially resulting in serious adverse reactions. To evaluate its potential to interact with co-administered drugs, the IC value of phase I cytochrome P450 enzymes (CYPs), phase II UDP-glucuronyltransferases (UGTs) and hepatic uptake transporters (organic cation transporters (OCTs), organic anion transporter polypeptides (OATPs) and Na-taurocholate cotransporting polypeptides (NTCPs)) were examined in vitro by LC-MS/MS. Diosmetin showed strong inhibition of CYP1A2 in a concentration-dependent manner. The intensity of the inhibitory effect was followed by CYP2C8, CYP2C9, CYP2C19 and CYP2E1. For CYP2A6, CYP2B6, CYP2D6 and CYP3A4, diosmetin was found to have no significant inhibitory effects, and the induction effect on CYPs was not significant. For UGTs, diosmetin had a minimal inhibitory effect. In addition, the inhibitory effects of diosmetin on OATP and OCT1 were weak, and it had little effect on NTCP. This finding indicated that drug-drug interactions induced by diosmetin may occur through co-administration of drugs metabolized by CYP1A2.
香叶木素（3'，5，7 - 三羟基 - 4'- 甲氧基黄酮）是一种源自传统中草药的天然黄酮类化合物，因其具有抗癌、抗菌、抗氧化、雌激素样和抗炎活性，已被用于各种医药产品中。然而，黄酮类化合物可能会影响代谢酶并导致药物相互作用（DDI），降低联合用药的疗效，并可能导致严重的不良反应。为了评估其与联合用药相互作用的可能性，通过液相色谱 - 串联质谱法（LC - MS/MS）在体外检测了I相细胞色素P450酶（CYPs）、II相尿苷二磷酸葡萄糖醛酸转移酶（UGTs）和肝脏摄取转运体（有机阳离子转运体（OCTs）、有机阴离子转运多肽（OATPs）和牛磺胆酸钠共转运多肽（NTCPs））的IC值。香叶木素以浓度依赖性方式对CYP1A2表现出强烈抑制作用。抑制作用强度依次为CYP2C8、CYP2C9、CYP2C19和CYP2E1。对于CYP2A6、CYP2B6、CYP2D6和CYP3A4，发现香叶木素没有显著抑制作用，并且对CYPs的诱导作用也不显著。对于UGTs，香叶木素具有最小的抑制作用。此外，香叶木素对OATP和OCT1的抑制作用较弱，对NTCP几乎没有影响。这一发现表明，香叶木素诱导的药物相互作用可能通过与由CYP1A2代谢的药物联合给药而发生。
