کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5850218 1561768 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Metabolic characterization of meso-dihydroguaiaretic acid in liver microsomes and in mice
ترجمه فارسی عنوان
تعیین متابولیسم اسید مازو دی هیدروگلایرایتیک در میکروسوم های کبد و موش ها
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش تغذیه
چکیده انگلیسی


- MDGA is rapidly metabolized by CYP and UGT in HLMs and MLMs.
- Extensive metabolism causes poor bioavailability of MDGA in mice.
- MDGA exhibits selective CYP2E1 inhibitory activity in HLMs.
- MDGA-induced CYP2E1 inhibition is competitive.

meso-Dihydroguaiaretic acid (MDGA) is a major component of Myristica fragrans and Machilus thunbergii that is traditionally used as a spice and for medicinal purposes. Despite reports of various biological activities exerted by MDGA, there is no information regarding its metabolic properties. The purpose of this study was to determine the metabolic stability and cytochrome P450 (CYP) inhibitory potential of MDGA, using pooled human liver microsomes (HLMs) to characterize its metabolic properties. In addition, pharmacokinetic analysis was performed in mice treated intravenously (5 mg/kg) or orally (20 mg/kg) with MDGA for comparison with our in vitro results. The half-life of MDGA in HLMs and mouse liver microsomes incubated with NADPH, UDPGA or NADPH plus UDPGA was 25.41 and 22.74, 0.39 and 0.20 or 0.28 and 0.22 min, respectively. In our pharmacokinetic study, MDGA rapidly declined in plasma and had low bioavailability, which was attributable to extensive metabolism by UDP-glucuronosyltransferases and CYPs. Among CYP isoforms, CYP2E1 activity was selectively inhibited by MDGA through a competitive inhibitory mode, with an inhibitory constant (Ki) value of 13.1 µM. These results suggest that MDGA can be used as a selective CYP2E1 inhibitor in vitro, which warrants evaluation of the pharmacological significance of MDGA-induced CYP2E1 inhibition.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Food and Chemical Toxicology - Volume 76, February 2015, Pages 94-102
نویسندگان
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