Abstract:
AIM:To investigate the mechanisms underlying the isomer-selective distribution of 3-n-butylphthalide (NBP) hydroxylated metabolites, 3-hydroxy-NBP (3-OH-NBP) and 10-hydroxy-NBP (10-OH-NBP), across the blood brain barrier (BBB). METHODS:After oral administration of NBP (20 mg/kg) to rats, the pharmacokinetics of two major hydroxylated metabolites, 3-OH-NBP and 10-OH-NBP, in plasma and brains were investigated. Plasma and brain protein binding of 3-OH-NBP and 10-OH-NBP was also assessed. To evaluate the influences of major efflux transporters, rats were pretreated with the P-gp inhibitor tariquidar (10 mg/kg, iv) and BCRP inhibitor pantoprazole (40 mg/kg, iv), then received 3-OH-NBP (12 mg/kg, iv) or 10-OH-NBP (3 mg/kg, iv). The metabolic profile of NBP was investigated in rat brain homogenate. RESULTS:After NBP administration, the plasma exposure of 3-OH-NBP was 4.64 times that of 10-OH-NBP, whereas the brain exposure of 3-OH-NBP was only 11.8% of 10-OH-NBP. In the rat plasma, 60%±5.2% of 10-OH-NBP was unbound to proteins versus only 22%±2.3% of 3-OH-NBP being unbound, whereas in the rat brain, free fractions of 3-OH-NBP and 10-OH-NBP were 100%±9.7% and 49.9%±14.1%, respectively. In the rats pretreated with tariquidar and pantoprazole, the unbound partition coefficient Kp,uu of 3-OH-NBP was significantly increased, while that of 10-OH-NBP showed a slight but not statistically significant increase. Incubation of rat brain homogenate with NBP yielded 3-OH-NBP but not 10-OH-NBP. CONCLUSION:The isomer-selective distribution of 10-OH-NBP and 3-OH-NBP across the BBB of rats is mainly attributed to the differences in plasma and brain protein binding and the efflux transport of 3-OH-NBP. The abundant 10-OH-NBP is not generated in rat brains.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Diao XX,Zhong K,Li XL,Zhong DF,Chen XYdoi
10.1038/aps.2015.64subject
Has Abstractpub_date
2015-12-01 00:00:00pages
1520-7issue
12eissn
1671-4083issn
1745-7254pii
aps201564journal_volume
36pub_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::Excessive and abnormal vessel growth plays a critical role in the pathogenesis of many diseases, such as cancer. Angiogenesis is one of the hallmarks of cancer growth, invasion, and metastasis. Discovery of novel antiangiogenic agents would provide new insights into the mechanisms of angiogenesis, as well as potential...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-019-0224-x
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abstract:AIM:To investigate the proliferation of vascular smooth muscle cells (VSMC) affected by ginsenoside Rg1 and further explore the molecular mechanism of ginsenoside Rg1 using proteomics. METHODS:The proliferation of VSMC was measured by MTS assay kit and flow cytometry. Proteomic alterations were analyzed using two-dime...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00331.x
更新日期:2006-08-01 00:00:00
abstract:AIM:To investigate the effect of chymase on the mucin secretion from human bronchial epithelial cells. METHODS:Primarily-cultured human bronchial epithelial (PCHBE) cells and normal human bronchial epithelial (NHBE) cells were cultured with chymase or other stimulus in a mixture of bronchial epithelial growth medium (...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
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abstract:AIM:To study the effects of dl-praeruptorin A (Pd-Ia) on nucleus factor-kappaB (NF-kappaB) activativity and tumor necrosis factor-alpha (TNF-alpha) expression in ischemia-reperfusion (I/R) myocardium. METHODS:Langendorff's isolated rat heart was subjected to a 10-min ischemia followed by a 30-min reperfusion. NF-kappa...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-01-01 00:00:00
abstract:AIM:Bufalin is one of the active components in the traditional Chinese medicine ChanSu that is used to treat arrhythmia, inflammation and cancer. BF211 is a bufalin derivative with stronger cytotoxic activity in cancer cells. The aim of this study was to identify the putative target proteins of BF211 and the signaling ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2016.30
更新日期:2016-07-01 00:00:00
abstract:AIM:To examine the role of cholinergic neurons in the nucleus raphe magnus (NRM) in noxious heat stimulation and in the effects of morphine-induced antinociception by rats. METHODS:After the cholinergic neuron selective toxin, AF64A, was microinjected into the NRM, we examined changes in the antinociceptive threshold ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-11-01 00:00:00
abstract::KCNQ1 channel is a member of the voltage-gated potassium channel KQT-like subfamily. The KCNQ1 gene has recently been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). In the present study, we examined the effects of KCNQ1 variants on the therapeutic response to modified-release gliclazide (gli...
journal_title:Acta pharmacologica Sinica
pub_type: 临床试验,杂志文章
doi:10.1038/aps.2016.103
更新日期:2017-01-01 00:00:00
abstract::Retinoid X receptor-α (RXRα), a unique member of the nuclear receptor superfamily, represents an intriguing and unusual target for pharmacologic interventions and therapeutic applications in cancer, metabolic disorders and neurodegenerative diseases. Despite the fact that the RXR-based drug Targretin (bexarotene) is c...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2014.109
更新日期:2015-01-01 00:00:00
abstract:AIM:To test the hypothesis that PI3K/Akt/eNOS signaling has a protective role in a murine model of ventilation associated lung injury (VALI) through down-regulation of p38 MAPK signaling. METHODS:Male C57BL/J6 (wild-type, WT) or eNOS knockout mice (eNOS(-/-)) were exposed to mechanical ventilation (MV) with low (LV(T)...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2009.190
更新日期:2010-02-01 00:00:00
abstract:AIM:To investigate the effects of 3-n-butylphthalide (NBP) on apoptosis induced by transient focal cerebral ischemia in rats, compare the action potency of s-(-)-, r-(+)- and (+/-)-NBP, and clarify the enantiomer that played a main role. METHODS:DNA fragmentation was detected by the terminal deoxynucleotidyl transfera...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-08-01 00:00:00
abstract:AIM:Probucol, an anti-hyperlipidemic drug, has been reported to exert antitumor activities at various stages of tumor initiation, promotion and progression. In this study we examined whether the drug affected glioma cell growth in vitro and the underlying mechanisms. METHODS:Human glioma U87 and glioblastoma SF295 cel...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,收录出版
doi:10.1038/aps.2014.88
更新日期:2014-12-01 00:00:00
abstract:AIM:To investigate the expression of advanced glycation end products (AGEs) and their receptor RAGE in the livers and blood vessels of rats with non-alcoholic steatohepatitis (NASH) and the effect of pentoxifylline (PTX) on liver and artery function in rats with NASH. METHODS:Sprague-Dawley rats were fed a high-fat di...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.110
更新日期:2010-10-01 00:00:00
abstract::For follicular lymphoma (FL) with grade 1/2, the complete response (CR) rate of the first-line R-CHOP treatment was significantly low. In this study, we assessed the rationality of the administration of rituximab for FL patients with grade 1/2 based on concentration-response relationship analyses. Thus, we conducted a...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-0479-2
更新日期:2020-07-31 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00462.x
更新日期:2006-12-01 00:00:00
abstract:AIM:To determine the release characteristics of a 5-fluorouracil-loaded poly (lactic acid) disc (5-FU-PLA-DS) and the effect of sustained drug delivery on the success of glaucoma filtration surgery in rabbit eyes. METHODS:A method of microspheres accumulated by excessive carriers was used in the preparation of the 5-F...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00833.x
更新日期:2008-09-01 00:00:00
abstract::Severe acute pancreatitis (SAP) is a severe acute abdominal disease. Recent evidence shows that intestinal homeostasis is essential for the management of acute pancreatitis. Chitosan oligosaccharides (COS) possess antioxidant activity that are effective in treating various inflammatory diseases. In this study we explo...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-00581-5
更新日期:2021-01-25 00:00:00
abstract:AIM:To determine whether deguelin can regulate the expression of nuclear factor kappa B (NF-kappaB) binding protein (IkappaBalpha) in U937 human leukemia cells and Raji human B lymphoma cells. METHODS:The localization of IkappaBalpha protein was investigated by using an immunofluorescence method. The expression of Ika...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00284.x
更新日期:2006-04-01 00:00:00
abstract::With the increasing incidence of drug-induced liver disease, attempts are being made to better understand the mechanisms behind these frequently life-endangering reactions. Analgesics and anti-inflammatory drugs are a major group exhibiting hepatotoxicity. We review research relating to these reactions, focusing on ul...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1111/j.1745-7254.2006.00278.x
更新日期:2006-03-01 00:00:00
abstract::Due to the lack of typical clinical symptoms, the average delay time for diagnosis of pulmonary hypertension (PH) is longer than 2 years. It is urgent to find biomarkers for PH diagnosis. In this study we investigated whether plasma microRNAs (miRNAs) can be used as biomarkers for PH diagnosis. We used microarray to i...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2018.39
更新日期:2018-07-01 00:00:00
abstract:AIM:To investigate the effects of angiotensin II (Ang II) on corticotropin-releasing hormone (CRH) and argipressin (AVP) release from median eminence (ME) of hypothalamus during acute hypoxia in rats. METHODS:Simulated hypoxia was performed in a hypobaric chamber. CRH and AVP were determined by radioimmunoassay (RIA)....
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::Central nervous system (CNS) disorders represent a broad spectrum of brain ailments with short- and long-term disabilities, and nanomedicine-based approaches provide a new therapeutic approach to treating CNS disorders. A variety of potential drugs have been discovered to treat several neuronal disorders; however, the...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/s41401-020-0429-z
更新日期:2020-07-01 00:00:00
abstract::Resibufogenin (RBG) is a single compound isolated from Chansu, a traditional Chinese medicine obtained from the skin venom gland of the toad. Formulations of Chansu have been widely applied in China, Japan, and other Asian countries for a long time and are currently used as alternative medicines. However, there have b...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:
更新日期:2001-04-01 00:00:00
abstract:AIM:To investigate the effect of epigallocatechin gallate (EGCG) on angiotensin II (Ang II)-induced stress fiber formation and hyperpermeability in endothelial cells. METHODS:Human umbilical vein endothelial cells (HUVECs) were treated with Ang II in the absence or presence of EGCG or mitogen-activated protein kinases...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.75
更新日期:2010-10-01 00:00:00
abstract:AIM:To differentiate the electrophysiological characteristics of somatic action potentials (AP) from isolated Neo and Juv nodose sensory neurons (NSN) and those from slices of intact Juv and adult rat nodose ganglia. METHODS:For isolated cell recordings nodose ganglia from 3-8 d old Neo and 4 weeks old Juv rats were d...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract::Saw palmetto extract (SPE), an extract from the ripe berries of the American dwarf palm, has been widely used as a therapeutic remedy for urinary dysfunction due to benign prostatic hyperplasia (BPH) in Europe. Numerous mechanisms of action have been proposed for SPE, including the inhibition of 5alpha-reductase. Toda...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2009.1
更新日期:2009-03-01 00:00:00
abstract:AIM:Targeting the VEGF/VEGF receptor (VEGFR) pathway has proved to be an effective antiangiogenic approach for cancer treatment. Here, we identified 6-((2-((3-acetamidophenyl)amino)pyrimidin-4-yl)oxy)-N-phenyl-1-naphthamide (designated herein as DW10075) as a novel and highly selective inhibitor of VEGFRs. METHODS:In ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2015.117
更新日期:2016-03-01 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:AIM:Epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent in green tea. The aim of this study is to investigate the effects of EGCG on proliferation and migration of the human colon cancer SW620 cells. METHODS:Proliferation and migration of SW620 cells were induced by the protease-activated receptor ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2011.139
更新日期:2012-01-01 00:00:00
abstract:AIM:To explore the possible association of different polymorphic forms of human alpha-estrogen receptor (ER-alpha) and aryl hydrocarbon receptor gene (Ahr) with the risk to senile dementia in farmers in Shanghai suburb. METHODS:Senile dementia patients (n=52) were examined for ER-alpha and Ahr gene polymorphism genoty...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00