JLX001, a novel compound with similar structure with cyclovirobuxine D (CVB-D), has been proved to exert therapeutical effects on permanent focal cerebral ischemia. However, the protective effects of JLX001 on cerebral ischemia/reperfusion (I/R) injury and its anti-apoptotic effects have not been reported. We investigated the efficacy of JLX001 in two pharmacodynamic tests (pre-treatment test and post-treatment) with rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R).
View Article and Find Full Text PDF(3β,5α,16α,20S)-4,4,14-trimethyl-3,20-bis(methylamino)-9,19-cyclopregnan-16-ol-dihydrochloride (JLX-001), a structural analogue of cyclovirobuxine D (CVB-D), is a novel compound from synthesis. This study aims to confirm the therapeutic effects of JLX001 on ischemic stroke (IS) and research its induction of autophagy function via 5'-AMP-activated protein kinase (AMPK)-Human Serine/threonine-protein kinase (ULK1) signaling pathway activation. The therapeutic effects of JLX001 were evaluated by infarct sizes, brain edema, neurological scores and proportion of apoptotic neurons in Sprague-Dawley (SD) rats with middle cerebral artery occlusion/reperfusion (MCAO/R).
View Article and Find Full Text PDFIschemic stroke is one of the leading health issues and the major cause of permanent disability in adults worldwide. Energy depletion and hypoxia occurring after ischemic stroke result in cell death, which activates resident glia cells and promotes the peripheral immune cells breaching into brain performing various functions even contradictory effects. The infiltration of immune cells may mediate neuron apoptosis and escalate ischemic damage, while it enhances neuron repair, differentiation, and neuroregeneration.
View Article and Find Full Text PDF(3β,5α,16α,20S)-4,4,14-trimethyl-3,20-bis(methylamino)-9,19-cyclopregnan-16-ol-dihydrochloride (JLX001), a derivative of cyclovirobuxine D (CVB-D), is a novel compound from synthesis. This study aims to confirm the therapeutic effect of JLX001 on cerebral ischemia and researchits antiplatelet and antithrombosis activities via thromboxane (TXA)/phospholipase C-β-3(PLCβ3)/protein kinase C (PKC) pathway suppression. The therapeutic effects of JLX001 was evaluated by infarct sizes, brain edema and neurological scores in Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO).
View Article and Find Full Text PDFNeuropathic pain is maladaptive pain caused by injury or dysfunction in peripheral and central nervous system, and remains a worldwide thorny problem leading to decreases in physical and mental quality of people's life. Currently, drug therapy is the main treatment regimen for resolving pain, while effective drugs are still unmet in medical need, and commonly used drugs such as anticonvulsants and antidepressants often make patients experience adverse drug reactions like dizziness, somnolence, severe headache, and high blood pressure. Thus, in this review we overview the anatomical physiology, underlying mechanisms of neuropathic pain to provide a better understanding in the initiation, development, maintenance, and modulation of this pervasive disease, and inspire research in the unclear mechanisms as well as potential targets.
View Article and Find Full Text PDFEur J Pharmacol
September 2017
1-(5-(1H-indol-5-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine (KFP-H008),a novel and potent potassium-competitive acid blocker for the treatment of acid secretion related diseases, has not been reported previously. In this study, we demonstrated that KFP-H008 inhibits basal acid secretion, 2-deoxy-D-glucose- (2DG-) stimulated gastric acid secretion in rats. KFP-H008 blocked histamine-stimulated acid secretion in rats and heidenhain pouch dogs and reversed acid output in isolated gastric perfusion under histamine stimulation.
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