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Mechanism of Tongsaimai tablet for atherosclerosis based on network pharmacology

基于网络药理学方法探讨通塞脉片治疗动脉粥样硬化的作用机制



全 文 :2016
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Vol41,No.9 May,2016

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MechanismofTongsaimaitabletforatherosclerosis
basedonnetworkpharmacology
LINa1,ZHANGXinzhuang1,WANGYanru1,CAOLiang1,DINGGang1,WANGZhenzhong1,XIAOWei1,XUXiaojie2
(1.StateKeyLaboratoryofNewtechforChineseMedicinePharmaceuticalProcesandJiangsu
KanionParmaceuticalCo.,Ltd.,Lianyungang222002,China;
2.ColegeofChemistryandMolecularEngineering,PekingUniversity,Beijing100871,China)
[Abstract] NetworkpharmacologymethodwasadoptedinthisstudytoexploretheactivecompoundsandmechanismofTongsaimai
tabletsforatherosclerosisInmoleculardockingandmoleculartargetproteinnetworkanalysis,97moleculesinTongsaimaitablets
showedgoodinteractionwiththeatherosclerosisrelatedtargetprotein(dockingscore≥7),and37moleculesofthemcouldactonmore
than2targets(≥2)withhigherbetweenness,suggestingthatthese37moleculesmightbethemainactivecompoundsgroupinTong
saimaitabletsforatherosclerosistreatmentFurthermore,thepredictedactivecompoundscontainedmoreflavonoidsandsaponins,re
mindingmoreatentionshouldbepaidonflavonoidsandsaponinsinstudyofefectivecompoundsandqualitystandardsofTongsaimai
tabletsTargetsnetworkanalysisshowedthat,theactivecompoundsofTongsaimaitabletscouldregulateinflammation,stabilize
plaque,protectvascularendothelialcel,regulatebloodlipidandinhibitbloodcoagulationthroughactingonthemain22targetpro
teins,suchasTollikereceptors(TLR1,TLR2),matrixmetaloproteinase(MMP1,MMP2,MMP3,MMP9),angiotensinconverting
·6071·
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•ê{|,}úû~@€/„‚ƒ/„…†_œ‡¯fˆ
enzyme(ACE),leukotrieneA4hydrolase(LTA4H),5lipoxidase(5LOX),peroxisomeproliferatorsactivatedreceptors(PPARα,
PPARγ)Theseactivecompoundscanparticipateinregulatingdiferentpathologicstagesofatherosclerosisandthustreatatherosclero
sisfinalyThisstudyrevealedthemainactivecompoundsandpossiblemechanismofTongsaimaitabletsfortreatmentofatherosclerosis
andmeanwhile,verifiedthecharacteristicsofmulticomponents,multitargetsandintegralregulationforTongsaimaitablets,providing
theoreticalreferencesforthefolowingsystematiclaboratoryexperimentsonefectivecompoundsandactionmechanismofTongsaimai
Tablet
[Keywords] traditionalChinesemedicine;Tongsaimaitablet;networkpharmacology;moleculardocking;atherosclerosis
doi:10.4268/cjcmm20160922
  
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·7071·
2016
y

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41
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Vol41,No.9 May,2016
Ÿ
1 
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Table1 Atherosclerosisrelatedtargets
ç QX
Uniprot
/<
PDB
/<
prostaglandinEsynthase PGES O14684 3DWW
yollikereceptor1 TLR1 Q15399 2Z7X
yollikereceptor2 TLR2 O60603 2Z7X
yollikereceptor4 TLR4 O00206 4G8A
coagulationfactorX FX P00742 3M36
coagulationfactorVI FVI P08709 2FLR
tissuetypeplasminogenactivator tPA P00750 1RTF
tumornecrosisfactor(α) TNFα P01375 2AZ5
interstitialcolagenase(matrixmetaloproteinase1) MMP1 P03956 966C
72kDatypeIVcolagenase(matrixmetaloproteinase2) MMP2 P08253 1HOV
stromelysin1(matrixmetaloproteinase3) MMP3 P08254 1B3D
matrixmetaloproteinase9 MMP9 P14780 1GKC
colagenase3(matrixmetaloproteinase13) MMP13 P45452 3ELM
arachidonate5lipoxygenase 5LOX P09917 3V99
leukotrieneA4hydrolase LTA4H P09960 3FH5
arachidonate5lipoxygenaseactivatingprotein 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
mitogenactivatedproteinkinase1 ERK2 P28482 3I5Z
MAPkinasep38alpha p38α Q16539 1KV1
MAPkinasep38beta p38β Q15759 3GC9
MAPkinasep38gamma p38γ P53778 1CM8
P2Y1receptor P2Y1 P47900 1Y36
peroxisomeproliferatoractivatedreceptoralpha PPARα Q07869 1I7G
peroxisomeproliferatoractivatedreceptordelta PPARσ Q03181 3GZ9
peroxisomeproliferatoractivatedreceptorgamma PPARγ P37231 3H0A
  
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;PDBRCSBProteinDataBank
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(degree)
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·9071·
2016
y

z À
41
ÁÀ

}
Vol41,No.9 May,2016
  Ÿ2 {|^#/îr=ˆ‰œ¡¶
Table2 Themoleculeswithhigherdegreeand/orbetweenness
incDTN
TCMN
/< _ª¨ {|^ r=
TCMC07292 loniflavone 9 0217
TCMC01FB8 ochnaflavone 9 0158
TCMC0802B 7stigmastenone3 5 0071
TCMC04BBB auroxanthin 5 0058
TCMC00D91 methylglycyrhetate 5 0048
TCMC0992C 4′Omethylochnaflavone 5 0044
TCMC0A809 glycyrhetol 5 0044
TCMC075DE gancaonolB 4 0127
TCMC00BED oleanolicacid 4 0041
TCMC02CB1 stigmasterol 4 0039
TCMC010BB 3′Omethylloniflavone 4 0035
TCMC03296 methyl18alphahydroxyglycyrhetate 4 0035
TCMC031DC glabrolide 4 0026
TCMC0A2C2 transβcarotene 3 0020
TCMC08484 uralenolide 3 0018
TCMC09877  3beta3hydroxy11,13(18)oleana
dien30oicacid
3 0016
TCMC05216 acetoxolone 3 0015
TCMC0B161 licoricesaponinH2 3 0013
TCMC09031 kanzonolJ 3 0008
TCMC097C4 gancaoninE 2 0050
TCMC00ADE sistosterol 2 0035
TCMC0CF89 glycycarpan 2 0035
TCMC02AE0 gancaoninO 2 0017
TCMC06D16 licoricesaponinE2 2 0017
TCMC022DC licoflavoneA 2 0012
TCMC03C58 gancaoninA 2 0006
TCMC0188F semilicoisoflavoneB 2 0005
TCMC06834 kanzonolF 2 0005
TCMC0BA50 glabrone 2 0005
TCMC01196 pyranocoumarin 2 0005
TCMC0981A  meester3beta3,24dihydroxy11,13
(18)oleanadien30oicacid
2 0004
TCMC053CB glycyrhetinicacid 2 0004
TCMC0B23D angelicide 2 0004
TCMC02C1F  Z3′,8′,3′alpha,7′alphatetrahydro6,
3′,7,7′alphadiligustilide8′one
2 0003
TCMC0951D 24hydroxyglycyrheticacidmethylester 2 0003
TCMC064AB phaseolinisoflavan 2 0002
TCMC04BA3 kanzonolI 2 0002
  
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Uniprot
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Q15399 TLR1 18 0216
P29474 eNOS 17 0187
P03956 MMP1 12 0155
P08254 MMP3 12 0148
P20292 FLAP 12 0085
P09960 LTA4H 10 0081
P01375 TNFα 9 0094
P12821 ACE 9 0084
P11597 CETP 8 0085
P45452 MMP13 8 0064
P08253 MMP2 5 0057
P09917 5LOX 5 0036
Q15759 p38β 4 0074
Q9BYF1 ACE2 4 0035
P14780 MMP9 4 0027
P08709 FVI 3 0033
Q07869 PPARα 3 0017
P37231 PPARγ 3 0002
O14684 PGES 2 1000
P17252 PKCα 2 0011
P00742 FX 2 0004
  
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