Amentoflavone is a potent broad-spectrum inhibitor of human UDP-glucuronosyltransferases

التفاصيل البيبلوغرافية
العنوان: Amentoflavone is a potent broad-spectrum inhibitor of human UDP-glucuronosyltransferases
المؤلفون: Yu-Sheng Shi, Jie Hou, Wei-Dong Zhang, Xia Lv, Wen-Zhong Hu, Da-Cheng Hao, Shuwen Liu, Ling Yang, Xin-Xin Wang, Guang-Bo Ge, Jianbin Zhang
المصدر: Chemico-Biological Interactions. 284:48-55
بيانات النشر: Elsevier BV, 2018.
سنة النشر: 2018
مصطلحات موضوعية: 0301 basic medicine, UGT1A4, Udp glucuronosyltransferases, Pharmacology, Amentoflavone, Toxicology, digestive system, 030226 pharmacology & pharmacy, Inhibitory Concentration 50, 03 medical and health sciences, chemistry.chemical_compound, Broad spectrum, 0302 clinical medicine, Non-competitive inhibition, Biflavonoids, Humans, Glucuronosyltransferase, Propofol, Chromatography, High Pressure Liquid, chemistry.chemical_classification, Chemistry, fungi, Biflavonoid, General Medicine, Recombinant Proteins, Kinetics, 030104 developmental biology, Toxicity, Microsomes, Liver, Microsome, Hymecromone
الوصف: Amentoflavone (AMF), an abundant natural biflavonoid found in many medicinal plants, displays various beneficial effects including anti-inflammatory, anti-oxidative and anti-cancer. Despite the extensive studies on pharmacological activities, the toxicity or undesirable effects of AMF are rarely reported. In this study, the inhibitory effects of AMF on human UDP-glucuronosyltransferases (UGTs) were carefully investigated. AMF displayed strong inhibition towards most of human UGTs including UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4 and 2B17, with the IC50 values ranging from 0.12 μM to 16.81 μM. Inhibition constants (Ki) of AMF against various human UGTs varied from 0.29 μM to 11.51 μM. Further investigation demonstrated that AMF was a noncompetitive inhibitor of UGT1A1 mediated NCHN-O-glucuronidation but functioned as a competitive inhibitor of UGT1A1 mediated 4-MU-O-glucuronidation. In addition, AMF was a competitive inhibitor of UGT1A4 mediated TFP-N-glucuronidation in both UGT1A4 and human liver microsomes, while functioned as a competitive inhibitor of UGT1A9 mediated propofol or 4-MU-O-glucuronidation. These findings demonstrated that AMF was a strong and broad-spectrum natural inhibitor of most human UGTs, which might bring potential risks of herb-drug interactions (HDIs) via UGT inhibition. Additionally, this study provided novel insights into the underlying mechanism of AMF-associated toxicity from the perspective of UGT inhibition.
تدمد: 0009-2797
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9df08038617355667f7bbdfe24b35c6dTest
https://doi.org/10.1016/j.cbi.2018.02.009Test
حقوق: CLOSED
رقم الانضمام: edsair.doi.dedup.....9df08038617355667f7bbdfe24b35c6d
قاعدة البيانات: OpenAIRE