简介：由于存在止痛剂的低效率和副作用，长期的疼痛在诊所成为了最复杂、困难的问题之一。Monoacylglycerol脂肪分解酵素(MAGL)是在endocannabinoid系统的必要hydrolase并且为疼痛的治疗作为一个潜在的目标被识别了。在现在的学习，我们设计了并且综合12tanshinoneIIA类似物并且对MAGL屏蔽了他们的活动。选择混合物在vivo为止痛活动被测试，与扭曲测试模型的醋酸。在测试混合物之中，加重III-3(IC50120nmol

简介：TanshinoneIIAisapharmacologicallyactivecompoundisolatedfromDanshen(Salviamiltiorrhiza),atraditionalChineseherbalmedicineforthemanagementofcardiacdiseasesandotherdisorders.Butitsunderlyingmolecularmechanismsofactionarestillunclear.ThepresentinvestigationutilizedadataminingapproachbasedonnetworkpharmacologytouncoverthepotentialproteintargetsofTanshinoneIIA.Networkpharmacology,anintegratedmultidisciplinarystudy,incorporatessystemsbiology,networkanalysis,connectivity,redundancy,andpleiotropy,providingpowerfulnewtoolsandinsightsintoelucidatingthefinedetailsofdrug-targetinteractions.Inthepresentstudy,twoseparatedrug-targetnetworksforTanshinoneIIAwereconstructedusingtheAgilentLiteratureSearch(ALS)andSTITCH(searchtoolforinteractionsofchemicals)methods.AnalysisoftheALS-constructednetworkrevealedatargetnetworkwithascale-freetopologyandfivetopnodes(proteintargets)correspondingtoFos,Jun,Src,phosphatidylinositol-4,5-bisphosphate3-kinase,catalyticsubunitalpha(PIK3CA),andmitogen-activatedproteinkinasekinase1(MAP2K1),whereasanalysisoftheSTITCH-constructednetworkrevealedthreetopnodescorrespondingtocytochromeP4503A4(CYP3A4),cytochromeP450A1(CYP1A1),andnuclearfactorkappaB1(NFκB1).Thediscrepancieswereprobablyduetothedifferencesinthedivergentcomputerminingtoolsanddatabasesemployedbythetwomethods.However,itisconceivablethatalleightproteinsmediateimportantbiologicalfunctionsofTanshinoneIIA,contributingtoitsoveralldrug-targetnetwork.Inconclusion,thecurrentresultsmayassistindevelopingacomprehensiveunderstandingofthemolecularmechanismsandsignalingpathwaysofinasimple,compact,andvisualmanner.

简介：ThisstudydevelopedapopulationpharmacokineticmodelforsodiumtanshinoneIIAsulfonate(STS)inhealthyvolunteersandcoronaryheartdisease(CHD)patientsinordertoidentifysignificantcovariatesforthepharmacokineticsofSTS.Bloodsampleswereobtainedbyintensesamplingapproachfrom10healthyvolunteersandsparsesamplingfrom25CHDpatients,andapopulationpharmacokineticanalysiswasperformedbynonlinearmixed-effectmodeling.Thefinalmodelwasevaluatedbybootstrapandvisualpredictivecheck.Atotalof230plasmaconcentrationswereincluded,137fromhealthyvolunteersand93fromCHDpatients.Itwasatwo-compartmentmodelwithfirst-orderelimination.Thetypicalvalueoftheapparentclearance(CL)ofSTSinCHDpatientswithtotalbilirubin(TBIL)levelof10μmol(L?1was48.7L(h?1withinterindividualvariabilityof27.4%,whereasthatinhealthyvolunteerswiththesameTBILlevelwas63.1L(h?1.Residualvariabilitywasdescribedbyaproportionalerrormodelandestimatedat5.2%.TheCLofSTSinCHDpatientswaslowerthanthatinhealthyvolunteersanddecreasedwhenTBILlevelsincreased.Thebootstrapandvisualpredictivecheckconfirmedthestabilityandvalidityofthefinalmodel.TheseresultssuggestedthatSTSdosageadjustmentmightbeconsideredbasedonTBILlevelsinCHDpatients.