简介:Inthepresentstudy,aseriesofnovelnitricoxide-hydrogensulfidereleasingderivativesof(S)-3-n-butylphthalide((S)-NBP)weredesigned,synthesized,andevaluatedaspotentialantiplateletagents.CompoundNOSH-NBP-5displayedthestrongestactivityininhibitingthearachidonicacid(AA)-andadenosinediphosphate(ADP)-inducedplateletaggregationinvitro,with3.8-and7.0-foldmoreeffectivenessthan(S)-NBP,respectively.Furthermore,NOSH-NBP-5couldreleasemoderatelevelsofNOandH2S,whichwouldbebeneficialinimprovingcardiovascularandcerebralcirculation.Moreover,NOSH-NBP-5couldrelease(S)-NBPwhenincubatedwithratbrainhomogenate.Inconclusion,thesefindingsmayprovidenewinsightsintothedevelopmentofnovelantiplateletagentsforthetreatmentofthrombosis-relatedischemicstroke.
简介:目的马尾藻类海草wightiiGreville是属于有大约200种类的Sargassaceae家庭的海洋的棕色的水藻。整个干燥植物粉末的ethanolic摘录包含了众多的phytoconstituents,包括flavonoids。学习在老鼠集中于马尾藻类海草wightii的anticancer活动。在二剂量的马尾藻类海草wightii(EESW)的ethanolic摘录铺平的方法被用来用DAL房间线在老鼠检验anticancer活动导致癌症。身体重量,可行、不能生存的肿瘤房间计数,吝啬的幸存时间,寿命的增加,和hematological参数为EESW的anticancer活动被观察。在老鼠的DAL房间的intraperitoneal接种显著地增加了的结果癌症房间计数。在在对待EESW的组癌症动物观察的癌症细胞数字的减少显示测试药在肿瘤细胞增长上有重要禁止的效果。有EESW的治疗也在肿瘤重量显示出重要减少,并且因此增加了对待DAL的老鼠的lifespan。另外,EESW管理显著地在对待DAL的老鼠恢复了hematological参数。现在的学习结果建议摘录提议的那个政府的结论提高了抗氧化剂潜力。因此,EESW拥有anticancer活动,这能从这研究被结束。
简介:Inthepresentstudy,theeffectsofPleurotusnebrodensispolysaccharide(PN-S)ontheimmunefunctionsofimmunosuppressedmiceweredetermined.Theimmunosuppressedmousemodelwasestablishedbytreatingthemicewithcyclophosphamide(40mg/kg/2d,CY)throughintraperitonealinjection.TheresultsshowedthatPN-SadministrationsignificantlyreversedtheCY-inducedweightloss,increasedthethymicandsplenicindices,andpromotedproliferationofTlymphocyte,Blymphocyte,andmacrophages.PN-SalsoenhancedtheactivityofnaturalkillercellsandincreasedtheimmunoglobulinM(IgM)andimmunoglobulinG(IgG)levelsintheserum.Inaddition,PN-Streatmentsignificantlyincreasedthephagocyticactivityofmouseperitonealmacrophages.PN-Salsoincreasedthelevelsofinterleukin-6(IL-6),tumornecrosisfactor-α(TNF-α),interferon-γ(INF-γ),andnitricoxide(NOS)insplenocytes.qRT-PCRresultsalsoindicatedthatPN-SincreasedthemRNAexpressionofIL-6,TNF-α,INF-γ,andnitricoxidesynthase(iNOS)inthesplenocytes.TheseresultssuggestthatPN-Streatmentenhancestheimmunefunctionofimmunosuppressedmice.Thisstudymayprovideabasisfortheapplicationofthisfungusinadjacentimmunopotentiatingtherapyagainstcancerandinthetreatmentofchemotherapy-inducedimmunosuppression.
简介:TagetonesA(1)andB(2),twonewmonocyclicditerpenoidswereisolatedfromthen-hexanefractionoffreshflowersofTagetesminutaL.(Asteraceae).Theirstructureswereestablishedbymultiplespectroscopicmethods(IR,HR-ESI-MS,and1D-,and2D-NMR),inadditiontocomparisonwithliteraturedata.Compound1showedcytotoxicactivitytowardsMCF7andA549cancercellswithIC_(50)valuesbeing4.68and4.24μmol·L~(-1),respectively,comparedtodoxorubicin(IC_(50)0.13and1.12μmol·L~(-1),respectively).Compound2alsoexhibitedsignificantactivityagainstHCT116cancercells(IC_(50),6.30μmol·L~(-1)).
简介:Cancerisamajorhealthconcernandleadingburdenoneconomyworldwide.Anincreasingeffortisdevotedtoisolationanddevelopmentofplant-deriveddietarycomponentsaseffectivechemo-preventiveproducts.Phytochemicalcompoundsfromnaturalresourcessuchasfruitsandvegetablesareresponsiblefordecreasingtheriskofcertaincancersamongtheconsumingpopulations.Apigenin,aflavonoidphytochemicalfoundinmanykindsoffruitsandvegetables,hasbeenshowntoexertsignificantbiologicaleffects,suchasanti-oxidant,anti-inflammatoryandmostparticularlyanti-neoplasticproperties.Thisreviewisintendedtosummarizethemostrecentadvancesintheanti-proliferativeandchemo-preventiveeffectsofapigeninindifferentcancermodels.Analysisofthedatafromthestudiedcancermodelshasrevealedthatapigeninexertsitsanti-proliferativeeffectsthroughmultipleandcomplexpathways.Thisguidedustodiscoversomecontroversialresultsabouttheexactroleofcertainmolecularpathwayssuchasautophagyintheanticancereffectsofapigenin.Further,therewerecumulativepositiveevidencessupportingtheinvolvementofcertainpathwayssuchasapoptosis,ROSandDNAdamageandrepair.Apigeninpossessesahighpotentialtobeusedasachemosensitizingagentthroughtheup-regulationofDR5pathway.Accordingtothesepreclinicalfindingswerecommendthatfurtherrobustunbiasedstudiesshouldconsiderthepossibleinteractionsbetweendifferentmolecularpathways.
简介:AIM:ToevaluatetheeffectofOcimumsanctumleafextractonthedietarysupplementationinthetransgenicDrosophilamodelofParkinson’sdisease.METHOD:TheeffectofOcimumsanctumleafextractwasstudiedonthetransgenicDrosophilamodeloffliesexpressingnormalhumanalphasynuclein(h-αs)intheneurons.O.sanctumextractatfinalconcentrationsof0.0428×10-4,0.87×10-4,and1.85×10-4g·mL-1ofdietwereestablishedandtheflieswereallowedtofeedfor21days.Theclimbingassayandlipidperoxidationweretakenasparametersforthestudy.RESULTS:ThesupplementationofO.sanctumextractshowedadose-dependentsignificantdelayinthelossofclimbingabilityandreductioninoxidativestressinthebrainofPDmodelflies.CONCLUSION:TheresultsofthepresentstudyshowedthattheO.sanctumextractispotentinreducingthePDsymptomsintransgenicDrosophilamodel.
简介:目的:探讨银杏内酯B衍生物(XQ)抗血小板聚集的作用及其机制。方法:运用比浊法测定静脉给药后PAF诱导的家兔血小板聚集作用,采用放射配基结合试验观察[3H]PAF与兔血小板受体特异性结合的作用。结果:XQ1.95、3.90、7.80mg·kg^-1对家兔血小板聚集的抑制率分别为29.8%、43.5%和55.2%(P〈0.01),PAF与家兔血小板膜上PAF受体结合的平衡解离常数(KD)=8.31×10^-5mmol·L^-1,最大结合容量(BMAX)=2.62×10^-9mmol/10^8血小板。XQ和银杏内酯B(GB)可抑制[3H]PAF与兔血小板受体的特异性结合,抑制常数(Ki)分别为8.72×10^-8、7.13×10^-7mol·L^-1。结论:XQ具有抗血小板聚集作用,Ki值接近,其拮抗PAF受体的能力与GB相似。
简介:免疫细胞化学技术和Westernblot分析证实MCF7adr细胞P-糖蛋白(PGP)过量表达,而MCF7细胞无PGP表达。1:60R1(复方R1)和1:90R1处理细胞2小时、3小时均使MCF7adr细胞PGP表达下降,并且与药物作用时间和浓度有关。Northernblot分析示MCFT7adr细胞mdr2mRNA高表达,而MCFT细胞无表达。1:60R1、1:90R1处理2小时或3小时均使MCF7adr细胞mdr1RNA表达降低,且随着时间的延长而更加明显。浓度(1:60R1,1:90R1)改变对耐药细胞mdr1mRNA表达下降的影响程度无明显差异。结果提示R1的逆转作用机理之一可能与其从蛋白质和mRNA水平使耐药细胞PGP表达下降,从而增加细胞内药物聚集量和抗癌药细胞毒性有关。
简介:Schisandrachinensis,atraditionalChinesemedicine(TCM),hasbeenusedtotreatsleepdisorders.Zebrafishsleep/wakebehavioralprofilingprovidesahigh-throughputplatformtoscreenchemicals,buthasneverbeenusedtostudyextractsandcomponentsfromTCM.Inthepresentstudy,theethanolextractofSchisandrachinensisanditstwomainlignincomponents,schisandrinandschisandrinB,werestudiedinzebrafish.Wefoundthattheethanolextracthadbidirectionalimprovementinrestandactivityinzebrafish.SchisandrinandschisandrinBwerebothsedativeandactivecomponents.WepredictedthatschisandrinwasrelatedtoserotoninpathwayandtheenthanolextractofSchisandrachinensiswasrelatedtoseoroninanddomapinepathwaysusingadatabaseofzebrafishbehaviors.ThesepredictionswereconfirmedinexperimentsusingCaenorhabditiselegans.Inconclusion,zebrafishbehaviorprofilingcouldbeusedasahigh-throughputplatformtoscreenneuroactiveeffectsandpredictmolecularpathwaysofextractsandcomponentsfromTCM.
简介:Ginkgoditerpenelactonesmeglumineinjection(GDLI)isacommerciallyavailableproductusedforneuroprotection.However,thepharmacokineticpropertiesoftheprototypesandhydrolyzedcarboxylicformsoftheprimarycomponentsinGDLI,i.e.,ginkgolideA(GA),ginkgolideB(GB),andginkgolideK(GK),haveneverbeenfullyevaluatedinbeagledogs.Inthiswork,asimple,sensitive,andreliablemethodbasedonultra-fastliquidchromatography-tandemmassspectrometry(UFLC-MS/MS)wasdeveloped,andtheprototypesandtotalamountsofGA,GB,andGKweredeterminedinbeagledogplasma.Theplasmaconcentrationsofthehydrolyzedcarboxylicformswerecalculatedbysubtractingtheprototypeconcentrationsfromthetotallactoneconcentrations.Forthefirsttime,thepharmacokineticsofGA,GB,andGKwerefullyassessedinthreeforms,i.e.,theprototypes,thehydrolyzedcarboxylicforms,andthetotalamounts,afterintravenousadministrationofGDLIinbeagledogs.Itwasshownthatginkgolidesprimarilyexistedinthehydrolyzedforminplasma,andtheratioofhydrolysatestoprototypeformsofGAandGBdecreasedgraduallytoahomeostaticratio.AllofthethreeformsofthethreeginkgolidesshowedlinearexposureofAUCtothedosages.GA,GB,andGKshowedaconstanthalf-lifeapproximately2.7,3.4,and1.2h,respectively,whichwereconsistentfortheformsatthreedoselevels(0.3,1.0,and3.0mg·kg~(-1))andafteraconsecutiveinjectionofGDLIfor7days(1.0mg·kg~(-1)).
简介:AnovelPleurotusnebrodensispolysaccharide(PN-S)waspurifiedandcharacterized,anditsimmune-stimulatingactivitywasevaluatedinRAW264.7macrophages.PN-SinducedtheproliferationofRAW264.7cellsinadose-dependentmanner,asdeterminedbytheMTTassay.AfterexposuretoPN-S,thephagocytosisofthemacrophageswassignificantlyimproved,withremarkablechangesinmorphologybeingobserved.FlowcytometricanalysisdemonstratedthatPN-SpromotedRAW264.7cellstoprogressthroughSandG2/Mphases.PN-Streatmentenhancedtheproductionsofinterleukin-6(IL-6),nitricoxide(NO),interferongamma(INF-γ),andtumornecrosisfactor-α(TNF-α)inthemacrophages,withup-regulationofmRNAexpressionsofinterleukin-6(IL-6),induciblenitricoxidesynthase(iNOS),interferongamma(INF-γ)andtumornecrosisfactor-α(TNF-α)beingobservedinadose-dependentmanner,asmeasuredbyqRT-PCR.Inconclusion,theseresultssuggestthatthepurifiedPN-Scanimproveimmunitybyactivatingmacrophages.
简介:目的:探讨银杏内酯B对谷氨酸诱导的人神经母细胞瘤(SH-SY5Y)细胞凋亡的保护作用及其机制。方法:用2mmol/L谷氨酸诱导SH-SY5Y细胞凋亡建立模型,以不同浓度的银杏内酯B(10、50和250μmol/L)进行保护,MTT比色法检测细胞存活率;Hoechst33258染色法观察药物作用后细胞凋亡的形态学变化;流式细胞仪检测细胞凋亡率;Fura-2/AM双波长荧光法测定细胞内钙离子浓度;Westernblot检测线粒体和胞浆中CytC蛋白的表达。结果:2mmol/L谷氨酸作用SH-SY5Y细胞24h后细胞存活率为0.721±0.013,与正常组相比明显降低;细胞核固缩裂解,呈凋亡特征性改变;细胞凋亡率为(13.27±0.08)%、细胞内钙离子浓度为359±11nmol/L,均明显升高。与凋亡组相比,银杏内酯B(10、50、250)μmol/L保护组细胞存活率分别为0.768±0.014、0.819±0.013、0.897±0.010,均明显升高;细胞核核固缩裂解减少,形态有所改善;细胞凋亡率分别为11.33±0.57、7.02±0.47、5.85±0.24;细胞内钙离子浓度为302±9nmol/L、243±9nmol/L、186±8nmol/L,均明显降低;Westernblot结果显示,与凋亡组相比银杏内酯B保护组可以显著减少细胞线粒体以及胞浆中CytC蛋白的含量。结论:银杏内酯B对谷氨酸诱导的SH-SY5Y细胞凋亡具有保护作用,其机制可能与银杏内酯B降低了细胞内钙离子的浓度及阻断了CytC从线粒体释放入胞浆中有关。
简介:目的:研究莪术醇对小鼠皮肤黑色素瘤B16-F10细胞凋亡的影响。方法:采用四氮唑盐(MTT)法检测不同浓度的莪术醇对B16-F10细胞增殖的影响;并用光学显微镜观察不同浓度的莪术醇对B16-F10细胞状态的影响;通过流式FITC-AnnexinV/PI双染法,检测不同浓度的莪术醇对细胞凋亡率的影响;通过间接荧光标记法检测不同浓度的莪术醇对细胞内活性氧水平的影响;通过罗丹明123染色,检测不同浓度的莪术醇对细胞内线粒体膜电位的影响。结果:不同浓度莪术醇处理B16-F10细胞24、48、72h,均可呈浓度、时间依赖性的抑制细胞增殖;显微镜观察到莪术醇可以引起细胞形态变圆,漂浮等细胞死亡现象。12.5、25、50、100μg/ml莪术醇作用48h后,诱导的细胞凋亡率分别为(19.5±3.4)%、(35.1±2.8)%、(45.9±4.1)%、(60.5±1.9)%,与对照组具有显著性统计学差异;诱导的细胞内活性氧水平的百分率分别为(6.9±1.8)%、(12.4±2.1)%、(20.9±3.1)%、(29.1±3.5)%,与对照组相比具有显著统计学差异。引起的线粒体膜电位的百分比分别为(40±1.1)%、(33.7±4.2)%、(27.3±2.5)%、(17.9±2.9)%,与空白对照组相比具有统计学差异。结论:莪术醇可以抑制B16-F10的增殖并促进细胞凋亡,其凋亡机制可能与细胞内活性氧组分的产生以及线粒体膜电位的变化有关。
简介:目的:探讨桂枝挥发油对核因子κB信号通路的影响。方法:制作LPS诱导的大鼠急性肺损伤模型,通过桂枝挥发油治疗后,采用ELISA法检测肺组织细胞核蛋白NF-κBP65含量和肺组织溶浆中磷酸化IκB-α、IL-1β的含量。结果:正常大鼠肺组织中NF-κBP65、磷酸化IκB-α和IL-1β仅有微量表达,LPS尾静脉注射后6h各其表达显著增高,桂枝挥发油高、中、低剂量组NF-κBP65、磷酸化IκB-α和IL-1β的含量均较模型组显著降低。结论:桂枝挥发油对急性肺损伤时高度活化的核因子κB信号通路有显著的抑制或拮抗作用,提示核因子κB信号通路是桂枝挥发油抗炎作用的主要靶点之一。