简介:Ginkgolicacids(GAs),primarilyfoundintheleaves,nuts,andtestaofginkgobiloba,havebeenidentifiedwithsuspectedallergenic,genotoxicandcytotoxicproperties.However,littleinformationisavailableaboutGAstoxicityinkidneysandtheunderlyingmechanismhasnotbeenthoroughlyelucidatedsofar.InsteadofGAsextract,therenalcytotoxicityofGA(15:1),whichwasisolatedfromthetestaofGinkgobiloba,wasassessedinvitrobyusingMDCKcells.TheactionofGA(15:1)oncellviabilitywasevaluatedbytheMTTandneutralreduptakeassays.Comparedwiththecontrol,thecytotoxicityofGA(15:1)onMDCKcellsdisplayedatime-anddose-dependentmanner,suggestingthecellsmitochondriaandlysosomesweredamaged.ItwasconfirmedthatGA(15:1)resultedinthelossofcellsmitochondrialtrans-membranepotential(ΔΨm).Inpropidiumiodide(PI)staininganalysis,GA(15:1)inducedcellcyclearrestattheG0/G1andG2/Mphases,influencingontheDNAsynthesisandcellmitosis.CharacteristicsofnecroticcelldeathwereobservedinMDCKcellsattheexperimentalconditions,asaresultofDNAagarosegelelectrophoresisandmorphologicalobservationofMDCKcells.Inconclusion,thesefindingsmightprovideusefulinformationforabetterunderstandingoftheGA(15:1)inducedrenaltoxicity.
简介:Consideringthegreatpotentialofnaturalproductsasanticanceragents,thepresentstudywasdesignedtoexplorethemolecularmechanismsresponsibleforanticanceractivitiesofMesuaferreastembarkextractagainsthumancolorectalcarcinoma.BasedonMTTassayresults,bioactivesub-fraction(SF-3)wasselectedforfurtherstudiesusingHCT116cells.Repeatedcolumnchromatographyresultedinisolationoflessactiveα-amyrinfromSF-3,whichwasidentifiedandcharacterizedbyGC-MSandHPLCmethods.α-amyrinandbetulinicacidcontentsofSF-3weremeasuredbyHPLCmethods.Fluorescentassaysrevealedcharacteristicapoptoticfeatures,includingcellshrinkage,nuclearcondensation,andmarkeddecreaseinmitochondrialmembranepotentialinSF-3treatedcells.Inaddition,increasedlevelsofcaspases-9and-3/7levelswerealsoobservedinSF-3treatedcells.SF-3showedpromisingantimetastaticpropertiesinmultipleinvitroassays.Multi-pathwayanalysisrevealedsignificantdown-regulationofWNT,HIF-1α,andEGFRwithsimultaneousup-regulationofp53,Myc/Max,andTGF-βsignallingpathwaysinSF-3treatedcells.Inaddition,promisinggrowthinhibitoryeffectswereobservedinSF-3treatedHCT116tumourspheroids,whichgiveahintaboutinvivoantitumorefficacyofSF-3phytoconstituents.Inconclusion,theseresultsdemonstratedthatanticancereffectsofSF-3towardscoloncancerarethroughmodulationofmultiplemolecularpathways.
简介:介绍Cystone是为各种各样的尿混乱在印度使用的同意的Ayurvedicpolyherbal专卖药品,包括urolithiasis。试图在urolithiasis把Cystone的保护的效果与导致hyperoxaluria的氧化应力和钙盐水晶免职作比较。方法乙烯乙二醇(例如)(0.75%,V/V)在喝,水被给老鼠28天与Cystone(500和750mg/kg身体重量)的同时的处理导致urolithiasis,并且urolithiasis的各种各样的尿风险因素和抗氧化剂标记被估计。例如结果处理导致增加的尿体积和降低的尿pH与盐的增加的尿排泄一起,在未经治疗的动物的钙和磷酸盐。这些变化在未经治疗的老鼠的肾引起了广泛的钙盐水晶免职,增加的类脂化合物peroxidation和抗氧化剂酶(草皮,过氧化氢酶和GPx)的减少的活动。Cystone阻止了这些hyperoxaluric表明并且在两剂量在对待的老鼠禁止了钙盐水晶免职。结论Cystone治疗由改进肾的织物抗氧化剂地位和多尿对导致hyperoxaluria的氧化应力和钙盐水晶免职提供保护。
简介:Marsdeniaetenacissimaeextract(MTE),commonlyknownasXiao-Ai-PinginChina,isatraditionalChineseherbmedicinecapableofinhibitingproliferationandmetastasisandboostingapoptosisinvariouscancercells.However,littleisknownaboutthecontributionofMTEtowardstumorangiogenesisandtheunderlyingmechanism.ThepresentstudyaimedtoevaluatetheeffectsofMTEontheproliferationandapoptosisofhumanumbilicalveinendothelialcells(HUVECs)andthemolecularism.3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium,innersalt(MTS)andPI-stainedflowcytometryassaysrevealedthatMTEdose-dependentlyreducedtheproliferationofHUVECsbyarrestingcellcycleatSphase(P<0.05).AnnexinV-FITC/PI-stainedflowcytometryconfirmedthatMTE(160μL·mL-1)enhancedtheapoptosisofHUVECssignificantly(P<0.001).Real-timequantitativeRT-PCRandWesternblotanalysesshowedanincreaseinBaxexpressionandasharplydeclineinBcl-2expression;caspase-3wasactivatedsimultaneouslyinadose-dependentmanner(P<0.05).Furtherstudyobservedthedose-dependentdown-regulationofvascularendothelialgrowthfactor(VEGF)receptor-2(VEGFR-2),P2Y6receptor(P2Y6R),andchemokine(C-Cmotif)ligand2(CCL-2),alongwiththeactivationofPKCδandup-regulationofp53inadose-dependentmannerinMTE-treatedselectedcells(P<0.05).Collectively,theresultsfromthepresentstudysuggestedthatMTEsuppressedtheproliferationbyattenuatingCCL-2-mediatedVEGF/VEGFR2interactionsandpromotedtheapoptosisthroughPKCδ-inducedp53-dependentmitochondrialpathwayinHUVECs,supportingthatMTEmaybedevelopedasapotentanti-cancermedicine.
简介:目的:利用人脐静脉内皮细胞体外培养模型,探讨肾上腺素刺激状态下海带多糖L01对内皮细胞的保护作用,以及其对其分泌的组织型纤溶酶原激活物(t-PA)的影响,从内皮细胞抗血栓功能方面探讨海带多糖L01对心血管系统的保护作用。方法:体外培养人脐静脉内皮细胞系ECV-304,用肾上腺素刺激24h、48h、72h采样,ELISA法测定HUVECs培养上清液中的t-PA含量,逆转录多聚酶链反应(RT-PCR)检测HUVEC细胞内t-PAmRNA的表达,其扩增产物经电泳后密度扫描及半定量分析。结果:肾上腺素模型组HUVECs培养液中t-PA(24h、48h)含量明显增加,;单给海带多糖对HUVECst-PA分泌无影响。海带多糖L01在肾上腺素刺激下给药24h,48h后t-PA抗原分泌明显降低(P〈0.01),且具有一定的量效关系,但HUVECst-PAmRNA表达各组均无明显差异。结论:肾上腺素可刺激内皮细胞分泌t-PA抗原,海带多糖L01对血管内皮具有一定的保护作用,减少肾上腺素刺激下HUVECs分泌t-PA,而对t-PAmRNA表达无明显影响。