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Vol41,No.9 May,2016
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MechanismofTongsaimaitabletforatherosclerosis
basedonnetworkpharmacology
LINa1,ZHANGXinzhuang1,WANGYanru1,CAOLiang1,DINGGang1,WANGZhenzhong1,XIAOWei1,XUXiaojie2
(1.StateKeyLaboratoryofNewtechforChineseMedicinePharmaceuticalProcesandJiangsu
KanionParmaceuticalCo.,Ltd.,Lianyungang222002,China;
2.ColegeofChemistryandMolecularEngineering,PekingUniversity,Beijing100871,China)
[Abstract] NetworkpharmacologymethodwasadoptedinthisstudytoexploretheactivecompoundsandmechanismofTongsaimai
tabletsforatherosclerosisInmoleculardockingandmoleculartargetproteinnetworkanalysis,97moleculesinTongsaimaitablets
showedgoodinteractionwiththeatherosclerosisrelatedtargetprotein(dockingscore≥7),and37moleculesofthemcouldactonmore
than2targets(≥2)withhigherbetweenness,suggestingthatthese37moleculesmightbethemainactivecompoundsgroupinTong
saimaitabletsforatherosclerosistreatmentFurthermore,thepredictedactivecompoundscontainedmoreflavonoidsandsaponins,re
mindingmoreatentionshouldbepaidonflavonoidsandsaponinsinstudyofefectivecompoundsandqualitystandardsofTongsaimai
tabletsTargetsnetworkanalysisshowedthat,theactivecompoundsofTongsaimaitabletscouldregulateinflammation,stabilize
plaque,protectvascularendothelialcel,regulatebloodlipidandinhibitbloodcoagulationthroughactingonthemain22targetpro
teins,suchasTollikereceptors(TLR1,TLR2),matrixmetaloproteinase(MMP1,MMP2,MMP3,MMP9),angiotensinconverting
·6071·
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enzyme(ACE),leukotrieneA4hydrolase(LTA4H),5lipoxidase(5LOX),peroxisomeproliferatorsactivatedreceptors(PPARα,
PPARγ)Theseactivecompoundscanparticipateinregulatingdiferentpathologicstagesofatherosclerosisandthustreatatherosclero
sisfinalyThisstudyrevealedthemainactivecompoundsandpossiblemechanismofTongsaimaitabletsfortreatmentofatherosclerosis
andmeanwhile,verifiedthecharacteristicsofmulticomponents,multitargetsandintegralregulationforTongsaimaitablets,providing
theoreticalreferencesforthefolowingsystematiclaboratoryexperimentsonefectivecompoundsandactionmechanismofTongsaimai
Tablet
[Keywords] traditionalChinesemedicine;Tongsaimaitablet;networkpharmacology;moleculardocking;atherosclerosis
doi:10.4268/cjcmm20160922
/
_
(atherosclerosis,AS)
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·7071·
2016
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Vol41,No.9 May,2016
1
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Table1 Atherosclerosisrelatedtargets
ç QX
Uniprot
/<
PDB
/<
prostaglandinEsynthase PGES O14684 3DWW
yollikereceptor1 TLR1 Q15399 2Z7X
yollikereceptor2 TLR2 O60603 2Z7X
yollikereceptor4 TLR4 O00206 4G8A
coagulationfactorX FX P00742 3M36
coagulationfactorVI FVI P08709 2FLR
tissuetypeplasminogenactivator tPA P00750 1RTF
tumornecrosisfactor(α) TNFα P01375 2AZ5
interstitialcolagenase(matrixmetaloproteinase1) MMP1 P03956 966C
72kDatypeIVcolagenase(matrixmetaloproteinase2) MMP2 P08253 1HOV
stromelysin1(matrixmetaloproteinase3) MMP3 P08254 1B3D
matrixmetaloproteinase9 MMP9 P14780 1GKC
colagenase3(matrixmetaloproteinase13) MMP13 P45452 3ELM
arachidonate5lipoxygenase 5LOX P09917 3V99
leukotrieneA4hydrolase LTA4H P09960 3FH5
arachidonate5lipoxygenaseactivatingprotein FLAP P20292 2Q7R
cholesterylestertransferprotein CETP P11597 4EWS
angiotensinconvertingenzyme ACE P12821 3L3N
angiotensinconvertingenzyme2 ACE2 Q9BYF1 1R4L
proteinkinaseCalphatype PKCα P17252 3IW4
proteinkinaseCetatype PKCη P24723 3TXO
nitricoxidesynthase,endothelial eNOS P29474 1M9J
mitogenactivatedproteinkinase1 ERK2 P28482 3I5Z
MAPkinasep38alpha p38α Q16539 1KV1
MAPkinasep38beta p38β Q15759 3GC9
MAPkinasep38gamma p38γ P53778 1CM8
P2Y1receptor P2Y1 P47900 1Y36
peroxisomeproliferatoractivatedreceptoralpha PPARα Q07869 1I7G
peroxisomeproliferatoractivatedreceptordelta PPARσ Q03181 3GZ9
peroxisomeproliferatoractivatedreceptorgamma PPARγ P37231 3H0A
ë
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·9071·
2016
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Vol41,No.9 May,2016
2 {|^#/îr=¡¶
Table2 Themoleculeswithhigherdegreeand/orbetweenness
incDTN
TCMN
/< _ª¨ {|^ r=
TCMC07292 loniflavone 9 0217
TCMC01FB8 ochnaflavone 9 0158
TCMC0802B 7stigmastenone3 5 0071
TCMC04BBB auroxanthin 5 0058
TCMC00D91 methylglycyrhetate 5 0048
TCMC0992C 4′Omethylochnaflavone 5 0044
TCMC0A809 glycyrhetol 5 0044
TCMC075DE gancaonolB 4 0127
TCMC00BED oleanolicacid 4 0041
TCMC02CB1 stigmasterol 4 0039
TCMC010BB 3′Omethylloniflavone 4 0035
TCMC03296 methyl18alphahydroxyglycyrhetate 4 0035
TCMC031DC glabrolide 4 0026
TCMC0A2C2 transβcarotene 3 0020
TCMC08484 uralenolide 3 0018
TCMC09877 3beta3hydroxy11,13(18)oleana
dien30oicacid
3 0016
TCMC05216 acetoxolone 3 0015
TCMC0B161 licoricesaponinH2 3 0013
TCMC09031 kanzonolJ 3 0008
TCMC097C4 gancaoninE 2 0050
TCMC00ADE sistosterol 2 0035
TCMC0CF89 glycycarpan 2 0035
TCMC02AE0 gancaoninO 2 0017
TCMC06D16 licoricesaponinE2 2 0017
TCMC022DC licoflavoneA 2 0012
TCMC03C58 gancaoninA 2 0006
TCMC0188F semilicoisoflavoneB 2 0005
TCMC06834 kanzonolF 2 0005
TCMC0BA50 glabrone 2 0005
TCMC01196 pyranocoumarin 2 0005
TCMC0981A meester3beta3,24dihydroxy11,13
(18)oleanadien30oicacid
2 0004
TCMC053CB glycyrhetinicacid 2 0004
TCMC0B23D angelicide 2 0004
TCMC02C1F Z3′,8′,3′alpha,7′alphatetrahydro6,
3′,7,7′alphadiligustilide8′one
2 0003
TCMC0951D 24hydroxyglycyrheticacidmethylester 2 0003
TCMC064AB phaseolinisoflavan 2 0002
TCMC04BA3 kanzonolI 2 0002
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Table3 Theproteintargetswithhigherdegreeand/orbetween
nessincDTN
Uniprot
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O60603 TLR2 21 0309
Q15399 TLR1 18 0216
P29474 eNOS 17 0187
P03956 MMP1 12 0155
P08254 MMP3 12 0148
P20292 FLAP 12 0085
P09960 LTA4H 10 0081
P01375 TNFα 9 0094
P12821 ACE 9 0084
P11597 CETP 8 0085
P45452 MMP13 8 0064
P08253 MMP2 5 0057
P09917 5LOX 5 0036
Q15759 p38β 4 0074
Q9BYF1 ACE2 4 0035
P14780 MMP9 4 0027
P08709 FVI 3 0033
Q07869 PPARα 3 0017
P37231 PPARγ 3 0002
O14684 PGES 2 1000
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,
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qMyzØÙ
[J].
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,2009,25
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Oòý
,
?.ö
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