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ABSTRACT Uliginosin B, a phloroglucinol isolated from Hypericum polyanthemum Klotzsch ex Reichardt, Hypericaceae, has antidepressant-like effect in the forced swimming test in rodents and inhibits monoamines neuronal reuptake without binding to their neuronal carriers. Studies showed the involvement of Na+,K+-ATPase brain activity in depressive disorders, as well as the dependence of neuronal monoamine transport from Na+ gradient generated by Na+,K+-ATPase. This study aimed at evaluating the effect of uliginosin B on Na+,K+-ATPase activity in mice cerebral cortex and hippocampus (1 and 3 h after the last administration) as well as the influence of veratrine, a Na+ channel opener, on the antidepressant-like effect of uliginosin B. Mice were treated (p.o.) with uliginosin B single (10 mg/kg) or repeated doses (10 mg/kg/day, 3 days). Acute administration reduced the immobility in the forced swimming test and tail suspension test and increased Na+,K+-ATPase activity in cerebral cortex 1 h after treating, whereas the repeated treatment induced the antidepressant-like effect and increased the Na+,K+-ATPase activity at both times evaluated. None treatment affected the hippocampus enzyme activity. Veratrine pretreatment prevented uliginosin B antidepressant-like effect in the forced swimming test, suggesting the involvement of Na+ balance regulation on this effect. Altogether, these data indicate that uliginosin B reduces the monoamine uptake by altering Na+ gradient.
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OBJECTIVE Tostudythehepatotoxicityofveratrinehydrochloride(VH)anditsmecha-nismoninductionofapoptosisinvitro.METHODS HepG2cellswereexposedtoVH0.1-0.6g·L-1 for 24 h,cell viability was examined by CCK-8 assay,and the morphologic changes in HepG2 cells were quantified.After the treatment with VH 0.1 -0.5 g·L-1 for 24 h,cell membrane injury was examined by detecting the release rate of lactate dehydrogenase (LDH).The effect on reactive oxygen species (ROS),mitochondrial membrane potential and apoptosis was detected by flow cytometry.The mRNA expression of p53,Bax,cytochrome c,caspase 9,caspase 3 was evaluated by real-time PCR. RESULTS HepG2cellviabilitywassignificantlyreducedfollowingexposuretoVH0.1-0.5g·L-1. The IC50 value was 0.4 g·L-1 .The 95%confidence limit was 0.2558-0.6965 g·L-1 .The LDH release rate,ROS and apoptosis rate of HepG2 cells were significantly increased after exposure to VH 0.1 -0.5 g·L-1 for 24 h (P<0.05,P<0.01 ),and the mitochondrial membrane potential markedly declined (P<0.05,P<0.01 ).The expression of p53,Bax,cytochrome c,caspase 9 and caspase 3 was increased(P<0.05,P<0.01).CONCLUSION VHhascytotoxicpotential.Damagetocell me mbrane and mitochondria and initiation of apoptosis-related genes of caspase 9 and caspase 3 mRNA expression may be the mechanis m of apoptosis.
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Objective To observe the effects of low dose of veratrine on the discharges of rat hippocampus pyramidal neurons,and to elucidate its possible cytological mechanism.Methods The discharge features of hippocampus CA1 pyramidal neurons of 14-day-aged healthy Sprague-Dawley rats induced by low dose(0.3～0.8?mol/L)of veratrine were observed by slice patch-clamp technique.Presynap- tic stimulation was given to Schaffer collaterals.Presynaptic receptor inhibitors such as 6-cyano-7-nitroquinoxaline-2,3-dione(CNQX, 5?mol/L),DL-2-amino-5-phosphonopentanoic acid(AP-5,12.5?mol/L),bicuculline(Bic,10?mol/L)and tetrodotoxin(TTX,40～80nmol/L)were used to investigate the influence on veratrine-induced epilepsy andⅠ-Ⅴcurves were plotted under these conditions.Elec- trophysiological mechanism of veratrine-induced epilepsy was elucidated on the basis of these experiments,Results After a perfusion with low dose of veratrine,the pyramidal neurons were found to discharge relatively fixed-mode slow wave epileptoid bursts accompanied with hyperpolarization of membrane potential.These epileptoid bursts were not blocked by a mixture of CNQX,AP-5 and Bic,but by low dose of TTX.After a perfusion with veratrine,Ⅰ-Ⅴrelationship tended to be nonlinear and the depolarization rectification was enhanced,which were reversed by administration of low dose of TTX.The subthreshold TTX-sensitive persistent sodium current of CA1 pyramidal cells was enhanced by veratrine in a voltage-dependent manner.Conclusion Inducing slow wave epileptoid bursts,the low dose of veratrine can remarkably change the discharge features of CA1 pyramidal neurons.Such epileptoid activities were not influenced by the synaptic receptor inhibitors,and were obviously related to the persistent sodium current.