Abstract:
AIM:The aim of this study was to study the effects of compound FLZ, a novel cyclic derivative of squamosamide from Annona glabra, on brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element-binding protein (CREB) signaling and neuronal apoptosis in the hippocampus of the amyloid precursor protein (APP)/presenilin-1 (PS1) double transgenic mice. METHODS:APP/PS1 mice at the age of 5 months and age-matched wild-type mice (WT) were intragastrically administered FLZ (150 mg/kg) or vehicle [0.05% carboxymethyl cellulose sodium (CMC-Na)] daily for 20 weeks. The levels of BDNF in the hippocampus of WT and APP/PS1 mice were then measured by immunohistochemistry and Western blot analysis. Neuronal apoptosis in mouse hippocampus was detected by Nissl staining. Expression of NGF, NT3, pTrkB (Tyr515)/TrkB, pAkt (Ser473)/Akt, pERK/ERK, pCREB (Ser133)/CREB, Bcl-2/Bax, and active caspase-3 fragment/caspase-3 in the hippocampus of WT and APP/PS1 mice was detected by Western blot analysis. RESULTS:Compared with vehicle-treated APP/PS1 mice, FLZ (150 mg/kg) significantly increased BDNF and NT3 expression in the hippocampus of APP/PS1 mice. In addition, FLZ promoted BDNF high-affinity receptor TrkB phosphorylation and activated its downstream ERK, thus increasing phosphorylation of CREB at Ser133 in the hippocampus of APP/PS1 mice. Moreover, FLZ showed neuroprotective effects on neuronal apoptosis by increasing the Bcl-2/Bax ratio and decreasing the active caspase-3 fragment/caspase-3 ratio in the hippocampus of APP/PS1 mice. CONCLUSION:FLZ exerted neuroprotection at least partly through enhancing the BDNF/TrkB/CREB pathway and inhibiting neuronal apoptosis in APP/PS1 mice, which suggests that FLZ can be explored as a potential therapeutic agent in long-term Alzheimer's disease therapy.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Li N,Liu GTdoi
10.1038/aps.2010.3subject
Has Abstractpub_date
2010-03-01 00:00:00pages
265-72issue
3eissn
1671-4083issn
1745-7254pii
aps20103journal_volume
31pub_type
杂志文章abstract:AIM:Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. METHODS:Male SD rats were injected with...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2014.127
更新日期:2015-03-01 00:00:00
abstract:AIM:Experimental studies found that cinacalcet (CINA) markedly attenuated vascular calcification in uremic rats, but its underlying mechanisms are still largely unknown. Recent evidence have demonstrated that endothelial cells (ECs) participate in ectopic calcification in part by mediating endothelial-to-mesenchymal tr...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2016.83
更新日期:2016-11-01 00:00:00
abstract:AIM:To investigate the mechanism of brain interleukin-1 beta (IL-1 beta) in reserpine-induced behavioral depression in rats. METHODS:Porsult swim test was used in the measurement of depressive behavior and ELISA was used in measurement of brain IL-1 beta. RESULTS:Intraperitoneal injection of reserpine (0, 4, 6, and 8...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract::Kushen (Radix Sophorae Flavescentis) has a long history of use for the treatment of tumors, inflammation and other diseases in traditional Chinese medicine. Compound Kushen Injection (CKI) is a mixture of natural compounds extracted from Kushen and Baituling (Rhizoma Smilacis Glabrae). The main principles of CKI are m...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2015.24
更新日期:2015-06-01 00:00:00
abstract:AIM:To study the effects of MN-9202, a new effective Ca2+ channel blocker, on platelet aggregation, 5-HT and TXB2 release, and calcium transport induced by platelet activators. METHODS:The mobilization of cytosolic-free calcium induced by thrombin in washed platelets was observed by Ca(2+)-sensitive fluorescent indica...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
abstract:AIM:To study the effect of nociceptin (orphanin FQ), a newly discovered heptadecapeptide, on cholinergic constrictions in isolated trachea and bronchus of rat. METHODS:The electric field stimulation (EFS) induced a monophasic constriction, which was due to an activation of the cholinergic nerves. RESULTS:Nociceptin 0...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2000-10-01 00:00:00
abstract:AIM:To investigate the effects of rapamycin on glutamate uptake in cultured rat astrocytes expressing N-terminal 552 residues of mutant huntingtin (Htt-552). METHODS:Primary astrocyte cultures were prepared from the cortex of postnatal rat pups. An astrocytes model of Huntington's disease was established using the ast...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2011.162
更新日期:2012-03-01 00:00:00
abstract:AIM:To investigate the protective effects of prostaglandin E(1) (PGE(1)) against H(2)O(2)-induced oxidative damage on human umbilical vein endothelial cells (HUVECs). METHODS:HUVECs were pretreated with PGE(1) (0.25, 0.50, and 1.00 micromol/L) for 24 h and exposed to H(2)O(2) (200 micromol/L) for 12 h, and cell viabil...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.23
更新日期:2010-04-01 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 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 study the neurotoxicity and toxicokinetics of norfloxacin (NFLX) in freely moving rats. METHODS:Rats were assigned randomly to four treatment groups that received a single iv dose of 50, 100, 200 mg/kg of NFLX and 0.9 % saline, respectively. Electroencephalogram (EEG) was continuously recorded with a computeriz...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-06-01 00:00:00
abstract::Natural compound valepotriate exhibits inhibitory activity against a number of cancers, but the effect of valepotriate against pancreatic cancer is unclear, and the structure-activity relationship of valepotriate has not been characterized. In this study, we performed a structure-based similarity search and found 16 h...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-019-0354-1
更新日期:2020-06-01 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::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 investigate the role of CYP2E1 in isoniazid (INH)-induced hepatotoxicity and the influence of rifampicin (RFP) on INH-induced liver injury. METHODS:Rats were treated with INH alone (100 mg/kg, ip) or co-administered with RFP (100 mg/kg, ig) for 10 d and 21 d. Hepatotoxicity was assayed by plasma enzymes (sALT, ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-05-01 00:00:00
abstract:AIM:To examine the in vitro antitumor activity of resveratrol against multiple myeloma (MM) cell lines (RPMI 8226, U266, and KM3), and the mechanisms involved. METHODS:The growth inhibition of resveratrol was determined by 3-(4, 5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The effect of resve...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00343.x
更新日期:2006-11-01 00:00:00
abstract:AIM:NLRP3 inflammasome plays an important role in renal injury and may be a therapeutic target in the treatment of patients with progressive chronic kidney disease. In this study we investigated whether angiotensin II (Ang II)-induced NLRP3 inflammasome activation was linked to endoplasmic reticulum stress (ERS) in hum...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2015.21
更新日期:2015-07-01 00:00:00
abstract:AIM:Our previous study demonstrated an siRNA-mediated, allele-specific silencing of mutant genes that cause amyotrophic lateral sclerosis. To improve siRNA design for better therapeutic use of RNA interference, we systematically tested the base-pairing mismatch strategy in the design of asymmetric siRNA. METHODS:A nat...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00740.x
更新日期:2008-02-01 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:AIM:To investigate the protective effects of hydrogen sulfide (H2S) against inflammation, oxidative stress and apoptosis in a rat model of resuscitated hemorrhagic shock. METHODS:Hemorrhagic shock was induced in adult male SD rats by drawing blood from the femoral artery for 10 min. The mean arterial pressure was main...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2013.96
更新日期:2013-12-01 00:00:00
abstract:AIM:In order to elucidate the molecular mechanism underlying the cardioprotection afforded by schisandrin B (Sch B), the effect of Sch B treatment on the sensitivity of mitochondria to Ca2+-stimulated permeability transition (PT) was investigated in rat hearts under normal and ischemia-reperfusion (I-R) conditions. RE...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00614.x
更新日期:2007-10-01 00:00:00
abstract:AIM:Both endothelin ETA receptor antagonists and angiotensin AT1 receptor antagonists lower blood pressure in hypertensive patients. A dual AT1 and ETA receptor antagonist may be more efficacious antihypertensive drug. In this study we identified the mode and mechanism of binding of imidazole series of compounds as dua...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2013.129
更新日期:2013-12-01 00:00:00
abstract:AIM:The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remo...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2016.22
更新日期:2016-06-01 00:00:00
abstract:AIM:To establish a 96-well plate based kinase assay using a recombinant vascular endothelial growth factor (VEGF) receptor 1 kinase domain protein. METHODS:A human VEGF receptor 1 kinase domain protein was expressed in E coli, and its activity was monitored by its ability of phosphorylating the polyE4Y substrate coate...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-02-01 00:00:00
abstract::Cerebral edema is a pathological hallmark of various central nervous system (CNS) insults, including traumatic brain injury (TBI) and excitotoxic injury such as stroke. Due to the rigidity of the skull, edema-induced increase of intracranial fluid significantly complicates severe CNS injuries by raising intracranial p...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-00503-5
更新日期:2020-10-01 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::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::Binding of a neurotransmitter to its ionotropic receptor opens a distantly located ion channel, a process termed allosteric activation. Here we review recent advances in the molecular mechanism by which the cys-loop receptors are activated with emphasis on the best studied nicotinic acetylcholine receptors (nAChRs). W...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2009.51
更新日期:2009-06-01 00:00:00
abstract:AIM:To investigate molecular mechanism of testis development and spermatogenesis. METHODS:A human testis cDNA microarray was hybridized with probes from human adult testis, embryo testis and human sperm, and the differential expressed clones were sequenced and analyzed. Expression of PIAS-NY gene was analyzed by RT-PC...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-08-01 00:00:00
abstract:AIM:Pirarubicin (THP) is recently found to be effective in treating patients with advanced, relapsed or recurrent high-grade osteosarcoma. In this study, the effects of THP on the multidrug-resistant (MDR) osteosarcoma cells were assessed, and the underlying mechanisms for the disruption of cell cycle kinetics by THP w...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.20
更新日期:2012-06-01 00:00:00