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Source: Acta Pharmacologica Sinica

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Total 122 results found since Jan 2013.

TRPM2: a candidate therapeutic target for treating neurological diseases.
Abstract Transient receptor potential melastatin 2 (TRPM2) is a calcium (Ca2+)-permeable non-selective cation channel belonging to the TRP ion channel family. Oxidative stress-induced TRPM2 activation provokes aberrant intracellular Ca2+ accumulation and cell death in a variety of cell types, including neurons. Aberrant TRPM2 function has been implicated in several neurological disorders including ischemia/stroke, Alzheimer's disease, neuropathic pain, Parkinson's disease and bipolar disorder. In addition to research identifying a role for TRPM2 in disease, progress has been made in the identification of physiolog...
Source: Acta Pharmacologica Sinica - April 19, 2018 Category: Drugs & Pharmacology Authors: Belrose JC, Jackson MF Tags: Acta Pharmacol Sin Source Type: research

The role of KATP channels in cerebral ischemic stroke and diabetes.
Abstract ATP-sensitive potassium (KATP) channels are ubiquitously expressed on the plasma membrane of cells in multiple organs, including the heart, pancreas and brain. KATP channels play important roles in controlling and regulating cellular functions in response to metabolic state, which are inhibited by ATP and activated by Mg-ADP, allowing the cell to couple cellular metabolic state (ATP/ADP ratio) to electrical activity of the cell membrane. KATP channels mediate insulin secretion in pancreatic islet beta cells, and controlling vascular tone. Under pathophysiological conditions, KATP channels play cytoprotect...
Source: Acta Pharmacologica Sinica - April 19, 2018 Category: Drugs & Pharmacology Authors: Szeto V, Chen NH, Sun HS, Feng ZP Tags: Acta Pharmacol Sin Source Type: research

Pharmacological approaches promoting stem cell-based therapy following ischemic stroke insults.
Abstract Stroke can lead to long-term neurological deficits. Adult neurogenesis, the continuous generation of newborn neurons in distinct regions of the brain throughout life, has been considered as one of the appoaches to restore the neurological function following ischemic stroke. However, ischemia-induced spontaneous neurogenesis is not suffcient, thus cell-based therapy, including infusing exogenous stem cells or stimulating endogenous stem cells to help repair of injured brain, has been studied in numerous animal experiments and some pilot clinical trials. While the effects of cell-based therapy on neurologic...
Source: Acta Pharmacologica Sinica - April 19, 2018 Category: Drugs & Pharmacology Authors: Zhu SZ, Szeto V, Bao MH, Sun HS, Feng ZP Tags: Acta Pharmacol Sin Source Type: research

Targeting RNS/caveolin-1/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: potential application for drug discovery.
Abstract Reactive nitrogen species (RNS) play important roles in mediating cerebral ischemia-reperfusion injury. RNS activate multiple signaling pathways and participate in different cellular events in cerebral ischemia-reperfusion injury. Recent studies have indicated that caveolin-1 and matrix metalloproteinase (MMP) are important signaling molecules in the pathological process of ischemic brain injury. During cerebral ischemia-reperfusion, the production of nitric oxide (NO) and peroxynitrite (ONOO-), two representative RNS, down-regulates the expression of caveolin-1 (Cav-1) and, in turn, further activates nit...
Source: Acta Pharmacologica Sinica - March 29, 2018 Category: Drugs & Pharmacology Authors: Chen HS, Chen X, Li WT, Shen JG Tags: Acta Pharmacol Sin Source Type: research

Discovery and development of NA-1 for the treatment of acute ischemic stroke.
Abstract Stroke creates a complex interplay of multiple signaing pathways including excitotoxicity, ionic imbalance, inflammation, oxidative stress and apoptosis. There are very few treatments that have been shown to be beneficial in acute stroke. Recent findings have provided insights into the pathophysiology and mechanisms of ischemic stroke, complementing the traditional glutamate hypothesis: the molecular interaction between PSD95 and GluN2B has been identified as a culprit in stroke-mediated excitotoxicity, leading to the discovery of NA-1, a peptide that disrupts that interaction, as a potent neuroprotective...
Source: Acta Pharmacologica Sinica - March 22, 2018 Category: Drugs & Pharmacology Authors: Ballarin B, Tymianski M Tags: Acta Pharmacol Sin Source Type: research

Diterpene ginkgolides protect against cerebral ischemia/reperfusion damage in rats by activating Nrf2 and CREB through PI3K/Akt signaling.
This study was designed to investigate the neuroprotective effects of DGMI components against ischemic stroke in vivo and in vitro. Acute cerebral ischemic injury was induced in rats by occlusion of the middle cerebral artery (MCA) for 1.5 h followed by 24 h reperfusion. The rats were treated with DGMI (1, 3 and 10 mg/kg, iv) at the onset of reperfusion and 12 h after reperfusion. Administration of DGMI significantly decreased rat neurological deficit scores, reduced brain infarct volume, and induced protein kinase B (Akt) phosphorylation, which prompted the nuclear translocation of nuclear factor-erythroid 2-related facto...
Source: Acta Pharmacologica Sinica - March 15, 2018 Category: Drugs & Pharmacology Authors: Zhang W, Song JK, Yan R, Li L, Xiao ZY, Zhou WX, Wang ZZ, Xiao W, Du GH Tags: Acta Pharmacol Sin Source Type: research

The role of TRPM2 channels in neurons, glial cells and the blood-brain barrier in cerebral ischemia and hypoxia.
Abstract Stroke is one of the major causes of mortality and morbidity worldwide, yet novel therapeutic treatments for this condition are lacking. This review focuses on the roles of the transient receptor potential melastatin 2 (TRPM2) ion channels in cellular damage following hypoxia-ischemia and their potential as a future therapeutic target for stroke. Here, we highlight the complex molecular signaling that takes place in neurons, glial cells and the blood-brain barrier following ischemic insult. We also describe the evidence of TRPM2 involvement in these processes, as shown from numerous in vitro and in vivo s...
Source: Acta Pharmacologica Sinica - March 15, 2018 Category: Drugs & Pharmacology Authors: Turlova E, Feng ZP, Sun HS Tags: Acta Pharmacol Sin Source Type: research

Apolipoprotein J as a predictive biomarker for restenosis after carotid endarterectomy: a retrospective study.
Abstract Carotid endarterectomy (CEA) is an effective surgical option for stroke prophylaxis in most patients. Restenosis after CEA can lead to re-intervention and adverse events, but the factors predicting restenosis are poorly understood. Apolipoprotein J (ApoJ) is considered to be a novel predictive factor of vascular restenosis and is associated with a large number of processes related to atherosclerosis and cell-cycle phases. The aim of this study was to elucidate the predictive value of Apo J in internal carotid artery (ICA) restenosis following CEA. This retrospective study examined all prospectively collec...
Source: Acta Pharmacologica Sinica - February 8, 2018 Category: Drugs & Pharmacology Authors: Maskanakis A, Patelis N, Karaolanis G, Davakis S, Schizas D, Perrea D, Klonaris C, Georgopoulos S, Liakakos T, Bakoyiannis C Tags: Acta Pharmacol Sin Source Type: research

Pure mechanistic analysis of additive neuroprotective effects between baicalin and jasminoidin in ischemic stroke mice.
In this study we used transcriptome analysis to explore the pure therapeutic mechanisms of BA, JA and their combination (BJ) contributing to phenotype variation and reversal of pathological processes. Mice with middle cerebral artery obstruction were treated with BA, JA, their combination (BJ), or concha margaritifera (CM). Cerebral infarct volume was examined to determine the effect of these compounds on phenotype. Using the hippocampus microarray and ingenuity pathway analysis (IPA) software, we exacted the differentially expressed genes, networks, pathways, and functions in positive-phenotype groups (BA, JA and BJ) by c...
Source: Acta Pharmacologica Sinica - January 18, 2018 Category: Drugs & Pharmacology Authors: Wang PQ, Liu Q, Xu WJ, Yu YN, Zhang YY, Li B, Liu J, Wang Z Tags: Acta Pharmacol Sin Source Type: research

Carnosine suppresses oxygen-glucose deprivation/recovery-induced proliferation and migration of reactive astrocytes of rats in vitro.
In this study we investigated the effects of carnosine, an endogenous water-soluble dipeptide (β-alanyl-L-histidine), on astrogliosis of cells exposed to oxygen-glucose deprivation/recovery (OGD/R) in vitro. Primary cultured rat astrocytes exhibited a significant increase in proliferation at 24 h recovery after OGD for 2 h. Pretreatment with carnosine (5 mmol/L) caused G1 arrest of reactive astrocytes, significantly attenuated OGD/R-induced increase in cyclin D1 protein expression and suppressed OGD/R-induced proliferation of reactive astrocytes. Carnosine treatment also reversed glycolysis and ATP production, which was e...
Source: Acta Pharmacologica Sinica - September 21, 2017 Category: Drugs & Pharmacology Authors: Ou-Yang L, Liu Y, Wang BY, Cao P, Zhang JJ, Huang YY, Shen Y, Lyu JX Tags: Acta Pharmacol Sin Source Type: research

Age-related differences in interferon regulatory factor-4 and -5 signaling in ischemic brains of mice.
Abstract Stroke is a disease that mainly affects the elderly. Since the age-related differences in stroke have not been well studied, modeling stroke in aged animals is clinically more relevant. The inflammatory responses to stroke are a fundamental pathological procedure, in which microglial activation plays an important role. Interferon regulatory factor-5 (IRF5) and IRF4 regulate M1 and M2 activation of macrophages, respectively, in peripheral inflammation; but it is unknown whether IRF5/IRF4 are also involved in cerebral inflammatory responses to stroke and whether age-related differences of the IRF5/IRF4 sign...
Source: Acta Pharmacologica Sinica - September 14, 2017 Category: Drugs & Pharmacology Authors: Zhao SC, Wang C, Xu H, Wu WQ, Chu ZH, Ma LS, Zhang YD, Liu F Tags: Acta Pharmacol Sin Source Type: research

Conversion and pharmacokinetics profiles of a novel pro-drug of 3-n-butylphthalide, potassium 2-(1-hydroxypentyl)-benzoate, in rats and dogs.
In this study, we investigated the conversion and pharmacokinetics profiles of dl-PHPB in vitro and in vivo. The conversion of dl-PHPB to dl-NBP was pH- and calcium-dependent, and paraoxonase was identified as a major enzyme for the conversion in rat plasma. The pharmacokinetics, tissue distribution and excretion of dl-PHPB were studied and compared with equal-molar doses of dl-NBP in rats and dogs. The in vivo studies showed that dl-PHPB could be quickly and completely converted to dl-NBP. The plasma concentration-time course of converted dl-NBP after intravenous dl-PHPB administration was nearly the same as that after eq...
Source: Acta Pharmacologica Sinica - September 14, 2017 Category: Drugs & Pharmacology Authors: Li J, Xu SF, Peng Y, Feng N, Wang L, Wang XL Tags: Acta Pharmacol Sin Source Type: research

Pharmacokinetic and metabolomic analyses of the neuroprotective effects of salvianolic acid A in a rat ischemic stroke model.
In conclusion, a larger amount of SAA enters the central nervous system in ischemia/reperfusion rats to facilitate its protective and regulatory effects on the perturbed metabolism. PMID: 28836583 [PubMed - as supplied by publisher]
Source: Acta Pharmacologica Sinica - August 24, 2017 Category: Drugs & Pharmacology Authors: Feng SQ, Aa N, Geng JL, Huang JQ, Sun RB, Ge C, Yang ZJ, Wang LS, Aa JY, Wang GJ Tags: Acta Pharmacol Sin Source Type: research

Xyloketal B alleviates cerebral infarction and neurologic deficits in a mouse stroke model by suppressing the ROS/TLR4/NF- κB inflammatory signaling pathway.
In conclusion, Xyl-B administered within 2 h after the onset of stroke effectively protects against focal cerebral ischemia; the underlying mechanism may be related to suppressing the ROS/TLR4/NF-κB inflammatory signaling pathway. PMID: 28552908 [PubMed - as supplied by publisher]
Source: Acta Pharmacologica Sinica - May 29, 2017 Category: Drugs & Pharmacology Authors: Pan N, Lu LY, Li M, Wang GH, Sun FY, Sun HS, Wen XJ, Cheng JD, Chen JW, Pang JY, Liu J, Guan YY, Zhao LY, Chen WL, Wang GL Tags: Acta Pharmacol Sin Source Type: research

Regulation of microglial activation in stroke.
Abstract When ischemic stroke occurs, oxygen and energy depletion triggers a cascade of events, including inflammatory responses, glutamate excitotoxicity, oxidative stress, and apoptosis that result in a profound brain injury. The inflammatory response contributes to secondary neuronal damage, which exerts a substantial impact on both acute ischemic injury and the chronic recovery of the brain function. Microglia are the resident immune cells in the brain that constantly monitor brain microenvironment under normal conditions. Once ischemia occurs, microglia are activated to produce both detrimental and neuroprote...
Source: Acta Pharmacologica Sinica - March 5, 2017 Category: Drugs & Pharmacology Authors: Zhao SC, Ma LS, Chu ZH, Xu H, Wu WQ, Liu F Tags: Acta Pharmacol Sin Source Type: research