In Vitro Bioactivation of Dihydrobenzoxathiin Selective Estrogen Receptor Modulators by Cytochrome P450 3A4 in Human Liver Microsomes:  Formation of Reactive Iminium and Quinone Type Metabolites

2005 ◽  
Vol 18 (4) ◽  
pp. 675-685 ◽  
Author(s):  
Zhoupeng Zhang ◽  
Qing Chen ◽  
Ying Li ◽  
George A. Doss ◽  
Brian J. Dean ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Selective Estrogen Receptor Modulators ◽  
Human Liver Microsomes ◽  
Cytochrome P450 3A4 ◽  
Estrogen Receptor Modulators ◽  
Receptor Modulators

scholarly journals Drug-Herb Interaction Between Selective Estrogen Receptor Modulators and Estrogenic Herbal Medicine Er-Xian Decoction in Bone in Vivo and in Vitro

2020 ◽  
Author(s):  
Ka-Ying Wong ◽  
Liping Zhou ◽  
Wenxuan Yu ◽  
Christina Chui Wa Poon ◽  
Man-Sau Wong
Keyword(s):  
Estrogen Receptor ◽  
Selective Estrogen Receptor Modulators ◽  
Serum Estradiol ◽  
Mineral Density ◽  
Alp Activity ◽  
Estrogen Receptor Modulators ◽  
Combined Use ◽  
Receptor Modulators

Abstract Background: Er-Xian decoction (EXD), a traditional Chinese Medicine for managing menopausal syndrome and osteoporosis in China, could exert osteoprotective action via activation of estrogen receptor (ERs) and regulation of serum estradiol without causing severe side effects. However, no fundamental studies have explored its potential interaction in the combined use of prescription drugs, Selective Estrogen Receptor Modulators (SERMs), regarding the osteogenic and uterotrophic effects. The present study evaluated the estrogenic effects of EXD and its potential interactions with tamoxifen and raloxifene in bone and uterus using a mature ovariectomized (OVX) Sprague-Dawley (SD) rat model and human osteoblastic MG-63 cells. Methods: Six-month-old female SD rats were randomly assigned to Sham-operated group or seven OVX groups: vehicle, 17ß-estradiol (E2, 1.0 mg/kg.day), Tamoxifen (Tamo, 1.0 mg/kg.day), Raloxifene (Ralo, 3.0 mg/kg.day), EXD (EXD, 1.6 g/kg.day), EXD+Tamoxifen (EXD+Tamo) and EXD+Raloxifene (EXD+Ralo). The effect of EXD on bodyweight, bone mineral density (BMD), bone microarchitecture, biochemical analysis of serum and urine, and uterus were evaluated. In addition, Alkaline phosphatase assay and activation of estrogen-responsive element mediated by EXD and in its combination with SERMs were investigated in MG-63 cells. Results: In vivo, EXD could interact with SERMs to modulate the serum estradiol, follicle-stimulating hormone, osteocalcin level as well as BMD and bone properties in OVX rats. Moreover, EXD could relieve the uterotrophic effect of SERMs. In vitro, EXD crude extract and EXD-treated serum could promote ALP activity. In particular, EXD-treated serum could interact with SERMs on regulating ALP activity in MG-63 cells. Conclusion: Our study demonstrated that EXD in vivo and EXD-treated serum in vitro did not weaken the osteogenic effect of SERMs. Interestingly, EXD seems to ameliorate the uterotrophic effects of SERMs. Therefore, the combined use of EXD and SERMs may be considered safe and effective in managing postmenopausal osteoporosis.

scholarly journals Effect of a New Prokinetic Agent DA-9701 Formulated with Corydalis Tuber and Pharbitidis Semen on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Hye Young Ji ◽  
Kwang Hyeon Liu ◽  
Ji Hyeon Jeong ◽  
Dae-Young Lee ◽  
Hyun Joo Shim ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Udp Glucuronosyltransferase ◽  
Index Value ◽  
Tuber Extract ◽  
Corydalis Tuber

DA-9701 is a new botanical drug composed of the extracts of Corydalis tuber and Pharbitidis semen, and it is used as an oral therapy for the treatment of functional dyspepsia in Korea. The inhibitory potentials of DA-9701 and its component herbs, Corydalis tuber and Pharbitidis semen, on the activities of seven major human cytochrome P450 (CYP) enzymes and four UDP-glucuronosyltransferase (UGT) enzymes in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. DA-9701 and Corydalis tuber extract slightly inhibited UGT1A1-mediated etoposide glucuronidation, with 50% inhibitory concentration (IC50) values of 188 and 290 μg/mL, respectively. DA-9701 inhibited CYP2D6-catalyzed bufuralol1′-hydroxylation with an inhibition constant (Ki) value of 6.3 μg/mL in a noncompetitive manner. Corydalis tuber extract competitively inhibited CYP2D6-mediated bufuralol1′-hydroxylation, with aKivalue of 3.7 μg/mL, whereas Pharbitidis semen extract showed no inhibition. The volume in which the dose could be diluted to generate an IC50equivalent concentration (volume per dose index) value of DA-9701 for inhibition of CYP2D6 activity was 1.16 L/dose, indicating that DA-9701 may not be a potent CYP2D6 inhibitor. Further clinical studies are warranted to evaluate thein vivoextent of the observedin vitrointeractions.

Sign in / Sign up

Export Citation Format

Share Document