นโยบายงานวิจัย /จรรยาบรรณนักวิจัย /ระดับคุณภาพบทความวิจัยตีพิมพ์ /ระดับคุณภาพผลงานวิชาการ /แหล่งทุน /ดาวน์โหลด /ฐานข้อมูลวิจัย /วิเคราะห์-สังเคราะห์งานวิจัย /ลิขสิทธิ์ /ข่าว


Inhibitory Potentials of Five Phytoestrogens from  Pueraria candollei  var. mirifica on CYP1A1 and CYP1A2 Proteins in Mouse Liver Microsomes and  in silico 

Author

- Waranya Chatuphonprasert, Kanokwan Jarukamjorn, Waraporn Putalun and Thaweesak Juengwattanatrakul


Journal

- Journal of Applied Biopharm aceutics and Pharmacokinetics

Volume

- 1

Year

- 2013

Publication type

- Research article (Inter)

Page list

- 5-11

Abstract

    Pueraria candollei  var.  mirifica (PM) is a Thai traditional medicinal plant for rejuvenation and estrogen
replacement therapy in menopausal women. CYP1A1 and CYP1A2 proteins are the members of hepatic cytochrome
P450 (CYP) enzymes to activate a procarcinogen, in which ethoxyresorufin  O -demethylase (EROD) and
methoxyresorufin O -demethylase (MROD) activities are the specific markers for CYP1A1 and CYP1A2, respectively. In
the present study, the effects of five phytoestrogens isolated form the bark of PM tuberous roots namely miroestrol,
deoxymiroestrol, khawkhurin, isomiroestrol, and methoxyisomiroestrol, on EROD and MROD activities were examined in
mouse hepatic microsomes, compared to a typical CYP1A1/2 inducer and substrate beta-napthoflavone (BNF). The
bindings of these five compounds to either CYP1A1 or CYP1A2 enzymes were analyzed using molecular docking with
homology modeling technique. Rank of the median inhibitory concentration (IC50
) of these compounds on EROD activity
corresponded to that of MROD, namely BNF > miroestrol > kwakhurin > deoxymiroestrol > methoxymiroestrol>
isomiroestrol, respectively. Interestingly, the binding pose energy of these compounds to CYP1A1 and CYP1A2 proteins
were consistent to those of inhibitory effects on EROD and MROD activities. The observations suggested for the first
time that the active phytoestrogens from PM possessed inhibitory potentials on CYP1A1 and CYP1A2  via  EROD and
MROD activities, respectively. Furthermore, the binding energy of the compounds to CYP1A1 and CYP1A2 proteins
might be a useful tool to predict the effects of a compound on these two CYP enzymes.


Keywords

    Pueraria candollei var.  mirifica , phytoestrogen, miroestrol, kwakhurin, CYP1A1, CYP1A2