کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5547191 | 1402784 | 2016 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identification and characterization of human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of ursolic acid
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کلمات کلیدی
RILDESIMetabolism pathwayUDPGAUGTsDDILC-MSVmaxnuclear magnetic resonance - رزونانس مغناطیسی هستهایHLMs - HLM هاLC-MS/MS - LC-MS / MSm/z - m / zUDP-glucuronosyltransferases - UDP-گلوکورونوزیل ترانسفرازUDP-glucuronic acid - اسید UDP-گلوکورونیکUrsolic acid - اسید اورسولیکstandard deviation - انحراف معیارNMR - تشدید مغناطیسی هستهای Drug–drug interactions - تعاملات داروییmaximum velocity - حداکثر سرعتSIM - سیم کارتLiquid chromatography mass spectrometry - طیف سنجی جرمی کروماتوگرافی مایعLiquid chromatography-tandem mass spectrometry - طیف سنجی جرمی کروماتوگرافی مایع دو طرفهHuman Liver Microsomes - میکروسومهای کبدی انسانیmass to charge ratio - نسبت جرم به شارژIntrinsic clearance - پاکسازی ذاتیClint - کلینت
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Identification and characterization of human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of ursolic acid Identification and characterization of human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of ursolic acid](/preview/png/5547191.png)
چکیده انگلیسی
This study aims to characterize the glucuronidation kinetics of ursolic acid (UA) in human liver microsomes (HLMs) and intestinal microsomes (HIMs) and identify the main UDP-glucuronosyltransferases (UGTs) involved. In our present study, only one type of UA glucuronide was observed after incubation with HLMs and HIMs respectively and was identified as a UA hydroxyl O-glucuronide. The glucuronidation of UA can be shown in HLMs and HIMs with Km values of 3.29 ± 0.16 and 3.74 ± 0.22 μM and Vmax values of 0.33 ± 0.03 and 0.42 ± 0.03 nmol/min/(mg protein). Among the 12 recombinant UGT enzymes investigated, UGT1A3 and UGT1A4 were identified as the major enzymes catalyzing the glucuronidation of UA [Km values of 2.58 ± 0.12 and 4.66 ± 0.60 μM, Vmax values of 0.72 ± 0.01 and 1.00 ± 0.06 nmol/min/(mg protein)]. The chemical inhibition study showed that the IC50 for hecogenin inhibition of UA glucuronidation was 51.79 ± 4.32 μM in HLMs. And chenodeoxycholic acid inhibited UA glucuronidation in HLMs with an IC50 of 28.26 ± 2.91 μM. In addition, UA glucuronidation in a panel of eight HLM was significantly correlated with telmisartan glucuronidation (r2 = 0.7660, p < 0.01) and trifluoperazine glucuronidation (r2 = 0.5866, p < 0.01) respectively. These findings collectively indicate that UGT1A3 and UGT1A4 were the main enzymes responsible for the glucuronidation of UA in human.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Drug Metabolism and Pharmacokinetics - Volume 31, Issue 4, August 2016, Pages 261-268
Journal: Drug Metabolism and Pharmacokinetics - Volume 31, Issue 4, August 2016, Pages 261-268
نویسندگان
Rui Gao, Mingyi Liu, Yu Chen, Chunhua Xia, Hong Zhang, Yuqing Xiong, Shibo Huang,