Inhibitory Effects of Sodium Ferulate on Proliferation of Rabbit Aortic Smooth Muscle Cells Induced by Oxidized LDL

The effects of sodium ferulate(SF), a water-soluble element of Chinese medicine Angelica sinensis diels, on cell-mediated oxidative modification of human low density lipoprotein(LDL) and proliferation of rabbit aortic smooth muscle cells(SMCs) were investigated. Using experimental models of proliferation of cultured rabbit aortic SMCs induced by oxidized LDL(ox-LDL), the extent of oxidation was determined by thiobarbituric acid reactive substances(TBARS) method, MTT colorimetry and 3H-thymidine(3H-TdR) incorporation were used to observe proliferation of SMCs. It showed that SF effectively inhibited cell-mediated oxidation induced by Cu2+ in a concentration-dependent manner. At the final concentration of 40, 80, 120 gmL-1, SF could significantly inhibit 3H-TdR incorporation and cell Proliferation in a dose-dependent manner. The results indicated that SF could, in vitro protect LDL against oxidative modification and inhibit the proliferation of SMC, which might be due to its free radical scavenging capacity.

Effects of sodium ferulate on the ultrarapid delayed rectifier K^+ current in human atrial myocytes

Objective：To study the effects of sodium ferulate on the ultrarapid delayed rectifier K^＋ current（IKur） in human atrial myocytes. Methods：Human atrial myocytes were isolated by enzyme dispersion method. IKur, in human atrial myocytes were recorded by using the whole cell patch clamp. The changes of IKur were compared in the absence and the presence of sodium ferulate. Results：There was no effect of 0.4 g/L sodium ferulate on I-V relation of IKur. However, 0.4 g/L sodium ferulate inhibited IKur to some degrees at each test pulse. The current densities of IKur at ＋60 mV decreased from 4.997 ± 0.35 PA/PF to 3.331 ± 0.26 PA/PF（n = 6, P 〈 0.05）. The inhibitory effect was concentration-dependent. IC50 was（0.41 ±0.03）g/L and the Hill coefficient was 0.95 ± 0.05. Conclusion：Sodium ferulate as a potassium channel blocker can inhibit IKur in human atrial myocytes effectively.

Protective effect of sodium ferulate on cardiac hypertrophy in spontaneously hypertensive rats

OBJECTIVE To investigate the inhibitory effect and mechanism of sodium ferulate(SF)on myocardial hypertrophy in spontaneously hypertensive(SHR).METHODS Forty 14-week-old SHR male rats were randomly divided into model group(SHR,receive distilled water)and SF treatment groups(SF 20,40 and 80 mg·kg^-1 per day,respectively).Age-matched male Wistar-Kyoto(WKY)rats gavaged with distilled water served as controls.After 12 weeks of treatment,the effects of SF on cardiac hypertrophy were evaluated using echocardiographic measurement,pathological analysis and the expression of atrial natriuretic peptide(ANP),myosin heavy chainβ(β-MHC)-a gene related to myocardial hypertrophy.In order to explore the mechanism of SF on myocardial hypertrophy,the calcium-sensing receptor(CaSR),calcineurin(CaN),nuclear factor of activated T cell 3(NFAT3),phosphorylation NFAT3(p-NFAT3),zinc finger transcription factor(GATA4),phosphorylation GATA4(p-GATA4),protein kinase Cβ(PKC-β),Raf-1,extracellular regulated protein kinase 1/2(ERK 1/2),phosphorylation ERK1/2(p-ERK 1/2)and mitogen-activated protein kinase phosphatase-1(MKP-1)were detected.RESULTS The myocardial hypertrophy parameters,myocardial cell cross section area,left ventricular wall thickness and expression of ANP and β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 were significantly increased,while the left ventricular cavity was significantly smaller,expression of p-NFAT3 and MKP-1 were significantly decreased,meanwhile,the ultra⁃structure of cardiomyocytes was significantly damaged in 26-week-old SHR rats.Notably,SF significantly ameliorated myocardial hyper⁃trophy in 26-week-old SHR rats;suppressed the overexpression of ANP,β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 and increased the expression of p-NFAT3 and MKP-1.CONCLUSION SF can inhibit cardiac hypertrophy in SHR rats,and the mechanism may be related to the inhibition of CaSR mediated signaling pathway.

Protective effects of sodium ferulate in vascular endothelial function during cardiopulmonary bypass

Objective Cardiopulmonary bypass (CPB) and its related ischemia reperfusion injury may cause endothelial cell injury. To study the protective effects of sodium ferulate in vascular endothelial function during CPB by testing the changes of vascular endothelial cell(CEC) ,nitric oxide(NO) and endothelin-1 (ET-1) in children with congenital heart disease. Methods Sixty patients

Effect of sodium ferulate on activation of postsynaptic density-95 after transient facol cerebral ischemia

It was confirmed that sodium ferulate (SF) could significantly improve neurologic function deficit, reduce cerebral infarct volume at 24 h after reperfusion, and weakened postsynaptic density-95 (PSD-95) activation in ische-mic area reacting to ischemia after transient middle cerebral artery occlusion ( MCAO) by Western immunoblot analy-

Effects of sodium ferulate on preventing steroid-induced femoral head osteonecrosis in rabbits

The aim of this study is to investigate the effects and possible mechanisms of sodium ferulate (SF) on anti-apoptosis in steroid-induced femoral head osteonecrosis in rabbits. Japanese white rabbits were randomly divided into three groups (control group, treatment group, and model group), each with 24 rabbits. The model and treatment groups were first injected with an intravenous dose of horse serum, 10 ml/kg, three weeks later with an intravenous dose of 7.5 ml/kg, and two weeks later with an intramuscular dose of methylprednisolone, 45 mg/kg, three times in order to establish rabbit models of osteonecrosis. Concurrently, the treatment group was injected with intravenous doses of SF 20 mg/kg for two weeks, once per day. Three time points, Weeks 2, 4, and 8, were selected after modeling was completed. Osteonecrosis was verified by histopathology with haematoxylin-eosin (HE) staining. The apoptosis rate of osteonecrosis was observed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The apoptosis expressions of caspase-3 and Bcl-2 were analyzed by immunohistochemistry and Western blot. The rabbit models of osteonecrosis were successfully established and observed by HE staining. SF was effective in intervening in apoptosis and decreasing the apoptosis rate in femoral head necrosis by the immunohistochemistry and TUNEL assay (P<0.01). Western blot analysis indicated that there were statistical significances in the protein levels of caspase-3 and Bcl-2 (P<0.01). SF has a protective effect by reducing the incidence of early steroid-induced femoral head necrosis in rabbits, effectively intervening in apoptosis through decreasing caspase-3 expression and up-regulating Bcl-2 expression.

Differentiation of Human Bone Marrow Stromal Cells into Neural-Like Cells Induced by Sodium Ferulate in vitro

Human marrow stromal cells （hMSCs） are multipotential stem cells, capable of differentiating into bone, cartilage, fat and muscle. Several recent reports demonstrated that hMSCs have been also differentiated into neural cells. However, only a few reported inducers are applicable for clinical use. This work is to explore the effects of sodium ferulate （SF） on differentiation of hMSCs into neural cells in vitro. We found that hMSCs could be induced to the cells with typical neural morphology when cultured with SF. The cells express neural proteins, such as nestin, neuron-specific enolase （NSE） and glial fibrillary acidic protein （GFAP）. About 30% of the hMSC-derived cells expressed nestin when cultured with SF for 3 h, but no expression was detected after 24 h. The percentages of positive cells for NSE or GFAP were about 67% and 39% separately at 6 h, and reached the plateau phage after treatment with SF for 3 days. The data suggest that SF can induce hMSCs to differentiate into neural-like cells in vitro. Cellular ＆ Molecular Immunology. 2005;2（3）：225-229.

Neuroprotective effect of sodium ferulate on transient focal cerebral ischemia by weakening activation of postsynaptic density-95 in rats

Objective： To investigate the effects of sodium ferulate （SF）, an intravenous drug made from traditional Chinese herbs, on activation of postsynaptic density-95 （PSD-95） and neuroprotection after transient cerebral artery occlusion in rats. Methods： Forty-six male Sprague-Dawley rats were randomized into 2 groups （ n = 23 in each group） ： the control group and the SF group. After anesthesia, the middle cerebral artery occlusion （MCAO） was conducted with the intraluminal filament technique. The neurological deficit was assessed with the method devised by Bederson et al.^ 8 The 2, 3, 4-triphenyltetrazolium chloride staining was used to assess the infarct volume. We adopted a modified six-point scale to conduct neurobehavioral evaluation. Immediately the activation of postsynaptic density-95 （ PSD- 95 ） was studied with Western blot analysis system in the cortex and striatum of rat brain. Results ： The neurologic deficit score of the SF group decreased substantially compared with that of the control group （ P 〈0.05）. The infarct volume of the control group （168.1 mm^3 ± 42.2 mm^3） was significantly larger than that of the SF group （61.5 mm^3 ± 28.7 mm^3 ） at 24 hours after reperfusion （P 〈 0.01 ）. And the rats showed some neurological deficit. The activity of PSD-95 in the SF group at most timepoints was less than that in the control group. No upregulation of PSD-95 protein could be detected in the contralateral cortex. Conclusions ： Sodium ferulate can induce a neuroproteetive effect against the transient focal cerebral isehemie injury and weaken the activation of PSD-95 in isehemie area after MCAO.

Study on Effect and Mechanism of Sodium Ferulate in Preventing and Treating Ozone Induced Lung Injury in Mice

Objective： To study the effect and mechanism of sodium ferulate （SF） in preventing and treating ozone （O3） induced lung oxidative injury in mice. Methods： Lung oxidative injury model mice were established by making them inhale O3. The activitY of anti-oxidase and membranous microviscosity in epithelial cells in the lung of mice were determined, and the ultrastructural change of lung tissues was observed with electromicroscopy. Results, Activities of superoxide dismutase （SOD） and giutathione peroxidase （GSH-Px） were reduced, while membranous lipo-microviscosity significantly increased in the pulmonary epithelial cells of model mice, revealing ultrastructural change. These abnormal changes were reversed by SF treatment, which was manifested as the significantly raised activities of SOD and GSH-Px after treatment with high and moderate doses of SF, showing a significant difference compared with those in the model group （P〈0.01）. Membranous lipo-microviscosity basically approached that in the control group （P〉0.05）; electron microscopic examination showed a basically normal morphological structure of pulmonary epithelial cells, with the change in lung injury significantly milder than that in the model group. Conclusion： O3 could induce oxidative injury of lungs in mice, and SF could enhance the anti-oxidation capacity of mice and scavenge the oxygen free radicals so as to alleviate the injury.

Effect of Sodium Ferulate on Fluidity and Morphology of Cell Membrane in Ozone Induced Lung Injury

To study the effect of sodium ferulate （SF）, an active component of Radix Angelica, on lung damage induced by ozone （O3）. Methods： Mice model of lung injury was induced by ozone inhalation and treated with SF. The level of lipid peroxide and microviscosity in alveolar epithelial cell membrane of the mice was determined, and the structural change of lung cells was observed by microscopy. Results： Ozone could increase the level of malondialdehyde （MDA） and the microviscosity in alveolar epithelial cell membrane, and induce inflammatory changes in morphologic structure. These abnormal changes were improved after SF administration, which was manifested as alleviation of heightened microviscosity, increase of membrane fluidity, as well as the basically normalized pulmonary cellular structure under microscope. Conclusion： SF has a preventive effect against oxidized pulmonary injury induced by ozone, the action of which could be through scavenging oxygen free radicals, reducing lipid peroxide production, increasing membranous fluidity and mitigating inflammatory changes in cell structure.