Abstract：
AIM:Catechol estrogens and 16alpha-hydroxy estrogen are important metabolites that cause carcinogenesis. This study was aimed to stud y the role of cytochrome P450 in estradiol metabolism. METHODS:The estradiol metabolites were determined with HPLC-ECD. Correlation of estradiol metabolites production between cytochrome P450 activity, the inhibitory effect of specific inhibitors and enzyme catalyzing kinetics were studied in cDNA-expressed P450 or human liver microsomes. RESULT:CYP1A2, CYP3A4, and CYP2C9 catalyze the estradiol 2-hydroxylation. CYP2C9, CYP2C19, and CYP2C8 have high activity in catalyzing 17beta-hydroxy dehydrogenation in cDNA expressed P450, but CYP1A2 is the most important enzyme in catalyzing estradiol 2-hydroxylation. Using furafyllin and troleandomycin to inhibit CYP1A2 and CYP3A4 in liver microsomes, it was found that the 2-hydroxylation had been inhibited about the same amount. This result suggests that in human liver microsomes CYP1A2 and CYP3A4 play an important role in 2-hydroxy estradiol formation. At low substrate concentration, 17beta -hydroxy dehydrogenation dominated the estradiol metabolism, but at high substrate concentration, 2-hydroxylation exceeded 17beta-hydroxy dehydrogenation to become the important mechanism. CONCLUSION:CYP1A2 and CYP3A4 are two important enzymes catalyzing the main estradiol 2-hydroxylation metabolism pathway at high substrate concentrations. 17beta-hydroxy dehydrogenation is the main metabolism pathway at low concentrations, and CYP2C9, CYP2C19, and CYP2C8 may have high catalyzing activity.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Cheng ZN,Shu Y,Liu ZQ,Wang LS,Ou-Yang DS,Zhou HHsubject
Has Abstractpub_date
2001-02-01 00:00:00pages
148-54issue
2eissn
1671-4083issn
1745-7254journal_volume
22pub_type
杂志文章abstract：AIM:To examine whether (-)-stepholidine (SPD) has a direct effect on the N-methyl- D-aspartic acid receptors (NMDAR) containing the NMDA receptor subunits NR2A or NR2B and to compare its effect with those of haloperidol (Hal) and clozapine (Cloz). METHODS:NMDAR was transiently expressed in human embryonic kidney 293 (...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00581.x
更新日期：2007-07-01 00:00:00
abstract：AIM:To determine whether mycophenolate mofetil (MMF) has beneficial effects on refractory idiopathic thrombocytopenic purpura (ITP) and the corresponding cellular mechanism. METHODS:Twenty refractory ITP patients resistant to corticosteroid and/or splenectomy and chemical therapy were given MMF 1.5-2.0 g/d orally for ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2005.00088.x
更新日期：2005-05-01 00:00:00
abstract：AIM:To investigate the anticancer effect of crocetin, a major ingredient in saffron, and its underlying mechanisms. METHODS:Cervical cancer cell line HeLa, non-small cell lung cancer cell line A549 and ovarian cancer cell line SKOV3 were treated with crocetin alone or in combination with vincristine. Cell proliferatio...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.109
更新日期：2011-12-01 00:00:00
abstract：:Dry eye disease (DED) is a multifactorial disorder of the tears and ocular surface characterized by manifestations of dryness and irritation. Although the pathogenesis is not fully illuminated, it is recognized that inflammation has a prominent role in the development and deterioration of DED. β-aminoarteether maleate...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-0484-5
更新日期：2020-08-03 00:00:00
abstract：AIM:To study the effects of tetrandrine (Tet) on extracellular Ca2+ influx and intracellular Ca2+ release in cultured calf basilar artery smooth muscle cells. METHODS:Free intracellular calcium was examined by a system of measurement of AR-CM-MIC, using Fura 2-AM as a fluorescent indicator. RESULTS:In the presence of...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-12-01 00:00:00
abstract：AIM:To test the ability of huperzine B (HupB) to alleviate injury from oxygen-glucose deprivation (OGD) in the rat pheochromocytoma line PC12 cells. METHODS:After OGD for 3 h and reoxygenation for 24 h, neuronal morphology was observed by phase-contrast microscopy; cell survival was quantified by the reduction of MTT;...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-12-01 00:00:00
abstract：AIM:To search for novel effective P-glycoprotein (P-gp) reversal agents in the blood-brain barrier (BBB). METHODS:Using rhodamine123 (Rh123) to examine the functional activity of P-gp in cultured bovine brain capillary endothelial cells (BCEC) and screen various principles on P-gp modulation in BBB. RESULTS:All of te...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-07-01 00:00:00
abstract：AIM:To investigate the effects of pravastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on impaired endothelium-dependent relaxation induced by lysophosphatidylcholine (LPC), the major component of oxidized low-density lipoprotein, in rat thoracic aorta. METHODS:Both the endotheliu...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2005.00013.x
更新日期：2005-01-01 00:00:00
abstract：AIM:To evaluate the pharmacokinetics of L-threonate after single or multiple oral administrations and its safety profile in healthy Chinese volunteers. METHODS:This was an open-label, single- and multiple-dose study. The subjects were assigned to receive a single dose, 675, 2025, or 4050 mg, of calcium L-threonate (n=...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.138
更新日期：2011-12-01 00:00:00
abstract：:Over half of patients with BRCA1-deficient cancers do not respond to treatment with poly(ADP-ribose) polymerase (PARP) inhibitors. In this study, we report that a combination of 53BP1 and BRCA1 may serve as a biomarker of PARP inhibitor sensitivity. Based on the mRNA levels of four homologous recombination repair (HR)...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2017.8
更新日期：2017-07-01 00:00:00
abstract：AIM:To study the protein and mRNA expressions of pro-inflammatory and anti-inflammatory cytokines in the brain of rats with atherosclerosis (AS) and the effects of Ginkgo biloba extract (GbE) on expressions of cytokines. METHODS:The experimental model of AS in rats were established by intraperitioneal injection of vit...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2005.00106.x
更新日期：2005-07-01 00:00:00
abstract：:Monoclonal antibodies are believed to be magic bullets and hold great potential for lots of biological process. About 100 μg of mAb109 was expressed in 5 × 106 cells after 10 days' immunization. 64Cu-NOTA-mAb109 was synthesized with the specific activity of 0.74 MBq/μg and high in vitro stability. The binding affinity...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-019-0294-9
更新日期：2020-01-01 00:00:00
abstract：AIM:To investigate modulation of antagonist and agonist binding to adenosine A1 receptors by MgCl2 and 5 -guanylimidodiphosphate (Gpp(NH)p) using rat brain membranes and the A1 antagonist [3H]-8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX) and the A1 agonist [3H]-2-chloro-N6-cyclopentyladenosine ([3H]CCPA). METHODS:Pa...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2003-08-01 00:00:00
abstract：:Terpene lactones are a class of bioactive constituents of standardized preparations of Ginkgo biloba leaf extract, extensively used as add-on therapies in patients with ischemic cardiovascular and cerebrovascular diseases. This investigation evaluated human pharmacokinetics of ginkgo terpene lactones and impact of the...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-018-0086-7
更新日期：2018-12-01 00:00:00
abstract：AIM:To investigate the antidepressant-like effects of a novel 5-HT3 receptor antagonist N-(benzo[d]thiazol-2-yl)-3-methoxyquinoxalin-2-carboxamide (6z) in acute and chronic murine models of depression. METHODS:5-HT3 receptor antagonism was examined in guinea pig ileum in vitro. A tail suspension test (TST) was used as...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2014.89
更新日期：2014-12-01 00:00:00
abstract：:Cerebral ischemia/reperfusion (I/R) results in harmful consequences during ischemic stroke, especially the disruption of the blood-brain barrier (BBB), which leads to severe hemorrhagic transformation through aggravation of edema and brain hemorrhage. Our previous study demonstrated that icariside II (ICS II), which i...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-0409-3
更新日期：2020-12-01 00:00:00
abstract：AIM:To study the protective effect of the polypeptide isolated from Chlamys farreri (PCF) on hairless mice skin damaged by ultraviolet A. METHODS:Enzymes and malondialdehyde (MDA) were determined by biochemical methods; the expressions of Bcl-2 protein and NOS protein were examined by immunohistochemical technique. Th...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-09-01 00:00:00
abstract：AIM:To identify the genetic variants of angiotensin II type 2 receptor (AT2R) gene in a Chinese population and to determine whether the AT2R gene polymorphisms are associated with essential hypertension (EH). METHODS:The detection of single nucleotide polymorphisms (SNPs) was performed in 19 subjects by a direct DNA s...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2003-11-01 00:00:00
abstract：:Astragaloside IV (AsIV) is an active saponin extracted from Astragalus membranaceus, which has shown cardioprotective effects in a number of experimental animals. In this study we investigated the molecular mechanisms by which AsIV attenuated the myocardial ischemia reperfusion (MI/R)-induced injury in vitro and in vi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-018-0082-y
更新日期：2019-05-01 00:00:00
abstract：AIM:To evaluate the pharmacokinetic interactions between theophylline and antofloxacin in vivo and in vitro. METHODS:A randomized, 5-day treatment and 3-way crossover design was documented in 12 healthy subjects. The subjects were orally administered with antofloxacin (400 mg on d 1 and 200 mg on d 2 to 5), theophylli...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,随机对照试验
doi：10.1038/aps.2011.78
更新日期：2011-10-01 00:00:00
abstract：:Hispidulin, a polyphenolic flavonoid extracted from the traditional Chinese medicinal plant S involucrata, exhibits anti-tumor effects in a wide array of human cancer cells, mainly through growth inhibition, apoptosis induction and cell cycle arrest. However, its precise anticancer mechanisms remain unclear. In this s...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2017.154
更新日期：2017-12-01 00:00:00
abstract：AIM:To study the stereoselectivity in pharmacokinetics of the enantiomers of trans-tramadol (trans-T) and its active metabolite, trans-O-demethyltramadol (M1) in human subjects. METHODS:Trans-T hydrochloride sustained-release tablets were taken orally by 12 healthy male volunteers. After a multiple dosage schedule, th...
journal_title：Acta pharmacologica Sinica
pub_type： 临床试验,杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：AIM:FTY720 is a new synthetic immunosuppressive agent which has a unique mechanism of action and induces long-term graft acceptance in rat and dog allotransplantation as prophylactic administration. The present study investigated whether FTY720 was able to rescue ongoing acute rejection of solid organ transplants in a ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2003-09-01 00:00:00
abstract：:Isothiocyanates are naturally occurring small molecules that are formed from glucosinolate precursors of cruciferous vegetables. Many isothiocyanates, both natural and synthetic, display anticarcinogenic activity because they reduce activation of carcinogens and increase their detoxification. Recent studies show that ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2009.50
更新日期：2009-05-01 00:00:00
abstract：AIM:To study the influence of angiotensin (Ang) II receptor antagonist (AT1) valsartan and angiotensin-converting enzyme (ACE) inhibitor fosinopril on the cardiac hypertrophy induced by catecholamine. METHODS:A cardiac hypertrophy model was produced by i.p. norepinephrine (NE) 1.5 mg.kg-1.d-1 x 15 d. The animals were ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2000-09-01 00:00:00
abstract：AIM:To study the expressions of vascular endothelial growth factor (VEG F), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), Tie-1, and Tie-2 in C57BL/6 mouse brain after permanent focal cerebral ischemia. METHODS:The mRNA levels of VEGF, Ang-1, Ang-2, Tie-1, and Tie-2 were measured by semiquantitative reverse transcri...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-05-01 00:00:00
abstract：:Wound healing impairment represents a particularly challenging clinical problem to which no efficacious treatment regimens currently exist. The factors ensuring appropriate intercellular communication during wound repair are not completely understood. Although protein-type mediators are well-established players in thi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1111/j.1745-7254.2005.00058.x
更新日期：2005-03-01 00:00:00
abstract：AIM:To explore the action of doxorubicin on vascular smooth muscle cells. METHODS:Isometric tension of denuded or intact thoracic aortic vessels was recorded and [Ca(2+)](i) in isolated aortic smooth muscle cells was measured by using Fluo-3. RESULTS:Doxorubicin induced phasic and tonic contractions in denuded vessel...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2009.145
更新日期：2009-11-01 00:00:00
abstract：AIM:To investigate the effect of edaravone (MCI-186), a free radical scavenger, against ischemia/reperfusion (I/R) injury in the rat retina. METHODS:Retinal ischemia was induced in male Sprague-Dawley rats by elevating intraocular pressure to 110 mmHg for 60 min. The rats were intraperitoneally injected with edaravone...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00822.x
更新日期：2008-07-01 00:00:00
abstract：:Pre-B-cell leukemia transcription factor 3 (PBX3) is a member of the PBX family and contains a highly conserved homologous domain. PBX3 is involved in the progression of gastric cancer, colorectal cancer, and prostate cancer; however, the detailed mechanism by which it promotes tumor growth remains to be elucidated. H...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-00599-9
更新日期：2021-02-01 00:00:00
