کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8544956 | 1561558 | 2018 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Amentoflavone is a potent broad-spectrum inhibitor of human UDP-glucuronosyltransferases
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Amentoflavone is a potent broad-spectrum inhibitor of human UDP-glucuronosyltransferases Amentoflavone is a potent broad-spectrum inhibitor of human UDP-glucuronosyltransferases](/preview/png/8544956.png)
چکیده انگلیسی
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 0.12â¯Î¼M to 16.81â¯Î¼M. Inhibition constants (Ki) of AMF against various human UGTs varied from 0.29â¯Î¼M to 11.51â¯Î¼M. 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 284, 25 March 2018, Pages 48-55
Journal: Chemico-Biological Interactions - Volume 284, 25 March 2018, Pages 48-55
نویسندگان
Xia Lv, Jian-Bin Zhang, Xin-Xin Wang, Wen-Zhong Hu, Yu-Sheng Shi, Shu-Wen Liu, Da-Cheng Hao, Wei-Dong Zhang, Guang-Bo Ge, Jie Hou, Ling Yang,