Total saponins of Aralia elata(Miq) Seem protect tumor necrosis factor-α-induced human umbilical vein endothelial cells via PI3K/Akt and NF-κB signal pathways

It is now thought that atherosclerosis,although due to enhanced lipid deposition,is mainly the result of a series inflammatory process.Total saponins of Aralia elata(Miq) Seem(TASAES) from the Chinese traditional herb Longya Araliachinensis L.,a folk medicine used for treating various diseases,increasing energy and improving the body′s ability to prevent hypoxia in Asian countries has attracted widespread attention.However,the ability of TASAES on inflammation-triggered vascular endothelial cell injury,a key early event in the pathogenesis of atherosclerosis,and its potential mechanisms of this protection have never been demonstrated.The present study determined the anti-inflammatory and anti-apoptoticactivities and protective mechanisms of the total aralosides of Araliaelata(Miq) Seem(TASAES) ameliorate tumor necrosis factor-α(TNF-α)-induced human umbilical vein endothelial cells(HUVECs) injury.Our results indicate that TASAES pretreatment provided cytoprotective effects by suppressing TNF-α-induced HUVECs apoptosis,mitochondrial membrane depolarization,caspase-3 activation,and modulation of inflammatory factors(IL-6,MCP-1 and VCAM-1),meanwhile inhibiting NF-κB transcription.Furthermore,the effect was correlated with the activation of the PI3K/Akt signal pathway.Blocking Akt activation with the PI3K inhibitor LY294002 effectively reversed the protective effect of TASAES against TNF-α-induced cell apoptosis.Moreover,the PI3K inhibitor partially blocked the effects of TASAES on the increasing of Bcl-2 and Bcl-xl protein expression,and inactivation of Bax protein expression.In conclusion,the results showed that TASAES decreased the inflammation and apoptosis of HUVECs caused by TNF-α treatment,and PI3K played a crucial role in enhancing cell sur.vival during this process.

Traditional Chinese medicines treating macrophage: A particular strategy for atherosclerosis

Atherosclerosis is a major cause of cardiovascular disease and one of the most deadly diseases in the world. Macrophages are the main contributors in the development of atherosclerosis, a target that drugs inhibit the inflammation and regulate lipid metabolism. In this review, we summarized the effects and mechanisms of traditional Chinese medicines and their bioactive compounds on atherosclerosis.

Shenkang Injection protects against diabetic nephropathy in streptozotocin(STZ)-induced mice through enhancement of anti-oxidant and anti-inflammatory activities

Objective:To investigate the protective effects and possible mechanisms of Shenkang Injection(SKI)on the diabetic nephropathy in streptozotocin-induced mice.Methods:STZ with the feeding of high fat diet(HFD)was used to induce diabetic mice.The balb/c mice and diabetic mice were then randomly divided into five groups:(1)control group,(2)model group,(3)alprostadil(Alp,1.5μg/kg)group,(4)SKI(30 ml/kg)group,(5)Alp(1.5μg/kg)+SKI(15 ml/kg)group.After six weeks'treatment,blood,urine and kidney tissues were collected for biochemical assay,EUSA assay,and pathological analysis.Results:Diabetic mice exhibited evident manifestations of diabetic nephropathy(DN),as indicated by increased 24-h urine volume,urinary albumin and kidney weight index(P<0.01),which could be attenuated by SKI treatment(P<0.01).SKI was further found to improve abnormal morphology in glomerulus with increased glomerular volume and to decrease urinary N-acetyl-b-D-glucpsaminidase(NAG),β2-microglobulin(β2-MG),and kidney injury molecules-1(KIM-1)levels(P<0.05,P<0.01).Plasma levels of anti-oxidant enzymes significantly reduced in the diabetic mice,and those decreases could be reversed by SKI and Alp treatments.Additionally,SKI obviously suppressed the diabetes-induced increases of proinflammatory cytokines(IL-6,IL-1βand TNF-α)(P<0.01).Meanwhile,SKI was found to effectively attenuate the diabetes-induced coagulation dysfunction,as evidenced by lengthening prothrombin and thrombin time,and decreasing plasma levels of fibrinogen(FIB),6-K-PGF1αand thromboxane B2(TXB2)(P<0.05,P<0.01).With SKI and Alp combined treatment,the anti-oxidant activities and improvements of coagulation dysfunction were enhanced.Conclusion:SKI possesses a remarkable property to prevent diabetic nephropathy.The improvements of kidney function and hypercoagulability by SKI were enhanced with Alp combined treatment.The molecular mechanisms underlying the protection of SKI against DN may be related to enhancing the antioxidant and anti-inflammatory activities,and improving the coagulation dysfunction.

Inhibition of Ovalitenin A on Proliferation of He La Cells via Apoptosis, G_2/M Cell Cycle Arrest, and Down- regulation of COX-2

Objective Ovalitenin A （1-（4-methoxybenzofuran-5-yl）-3-phenyl-2-propen-l-one） is a chalcone isolated from Millettia pulchra. The aim of the study was to investigate the antitumor effect of ovalitenin A on apoptosis in vitro and in vivo and to identify the mechanism involved. Methods The effect of ovalitenin A in human cervical cancer HeLa cells was detected by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （M-I-r） assay, morphological observation, flow cytometric measurement, Western blotting, and xenograft model. Results Ovalitenin A inhibited the proliferation of HeLa cells in a dose-dependent manner in vitro and in vivo and induced the apoptosis evidenced by characteristic apoptotic morphological changes, phosphatidylserine externalization, and activation of caspase-3. In addition, ovalitenin A induced G2/M cell cycle arrest and up-regulation of the Bax/Bcl-2 ratio. Furthermore, ovalitenin A decreased protein level of COX-2 and induced the loss of mitochondrial membrane potential. Conclusion These data suggest that ovalitenin A has the potential of anticancer properties for the treatment of cervical cancer.

Protective effects of combination of Xuesaitong and aspirin on cerebral ischemia and reperfusion injury in rats

Objective：To investigate the protective effects of the combination of Xuesaitong（XST）and aspirin on cerebral ischemia and reperfusion injury（CIRI）in rats,and further explore the underlying mechanisms.Methods：A total of 150 male Sprague-Dawley（SD）rats were randomly divided into five groups with 30rats in each group：sham group,middle cerebral artery occlusion/reperfusion（MCAO/R）model group,XST group,aspirin group,and XST＋aspirin group.Rats were pretreated with XST,aspirin,or XST＋aspirin for7 d.One hour after the last administration,a model of CIRI was induced by MCAO/R.Neurological deficits were assessed using Longa’s five-point scale.Cerebral edema was detected by the measurement of brain water content.The volume of cerebral infarction was determined by 2,3,5-triphenyltetrazolium chloride（TTC）staining.The activities of superoxide dismutase（SOD）,catalase（CAT）,and glutathione peroxidase（GSH-Px）,as well as levels of malonaldehyde（MDA）were detected by commercial kits.Enzyme-linked immunosorbent assay（ELISA）was used to determine the levels of interleukin-1（）,interleukin-4（IL-4）,interleukin-6（IL-6）,interleukin-10（IL-10）,tumor necrosis factor-alphamonocyte chemotactic protein 1（MCP-1）,and kynurenine in serum,cerebral cortex,and hippocampus of MCAO/R rats.The protein expression of nuclear factor erythroid 2-related factor（Nrf2）,heme oxygenase-1（HO-1）,I-kappa B alpha（IκBα）,and nuclear factor kappa B（B）/p65 in the cortex were analyzed by western blotting.Results：Treatment of XST,aspirin,and XST＋aspirin significantly alleviated the neurological deficits,cerebral edema,and cerebral infarct volume induced by MCAO/R.Treatment of XST,aspirin,and XST＋aspirin also reduced MDA,,MCP-1,and kynurenine levels,and increased SOD,CAT,GSH-Px,IL-4,and IL-10 levels in serum,cerebral cortex,and hippocampus of MCAO/R rats.Furthermore,treatment of XST,aspirin,and XST＋aspirin decreased the expression of nuclearB/p65 and increased the expression of IκBα,nuclear Nrf2,and HO-1.Importantly,the combination of XST and aspirin enhanced the protective effects of XST or aspirin treatment alone on CIRI in rats.Conclusion：The combination of XST and aspirin significantly inhibited oxidative stress and inflammation in serum,cerebral cortex,and hippocampus of MCAO/R rats.The combination of XST and aspirin exerted more protective effects than XST or aspirin treatment alone.The combination of XST and aspirin might provide the synergistic therapeutic effects on CIRI,and deserve further clinical investigation.

Combination of Shuxuetong and aspirin protects against cerebral ischemia/reperfusion injury through ameliorating coagulation and fibrinolysis system

Objective：To explore the influence of the combination of Shuxuetong（SXT）and aspirin on coagulation and fibrinolytic system of rats.Methods：Suture method was applied to establish focal cerebral ischemia-reperfusion injury models in rats.SD rats were randomly divided into sham group,middle cerebral artery occlusion/reperfusion（MCAO/R）group,aspirin group,SXT group,and SXT＋aspirin group（S＆A）.The neurological deficits were assessed according to Longa’s grade 5 scoring method.The cerebral edema was detected by measuring the content of water in brain tissue.The volume of cerebral infarction was observed by 2,3,5-Triphenyltetrazolium chloride（TTC）staining.Blood plasma was collected by abdominal aortic method to test maximum platelet aggregation rate and four blood coagulation.CD61,CD62p,6-keto prostaglandin F1αantithrombinⅢ（AT-Ⅲ）,D-dimer,plasminogen activator inhibitor-1（PAI-1）,tissue factor（TF）,tissue plasminogen activator（t-PA）,platelet thromboxaneand von Willebrand factor（v WF）content in rat plasma were detected by ELISA.Results：SXT combined with aspirin could improve the neurological deficits,alleviate cerebral edema,and decrease the cerebral infarct value.Compared with the sham operation group,fibrinogen（FIB）,6-AT-III,and t-PA in model group were significantly decreased;Compared with the model group,the above-mentioned indexes in SXT and aspirin treatment group were significantly increased.The prothrombin time（PT）,activated partial thromboplastin time（APTT）,thrombin time（TT）,D-dimer,PAI-1,TF,TXB2,and v WF of the model group were significantly increased;The above-mentioned indexes in blood SXT＋aspirin treated group were significantly decreased.There was a significant difference between the combined group and SXT group.The maximum concentration of plateletsin aspirin treated rats was significantly decreased,however,MPAR was reversed in SXT＋aspirin treated group.Conclusion：SXT combined with aspirin can effectively inhibit platelet activation,regulate the maximum concentration of platelets,and improve coagulation function and fibrinolysis system.