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Active compounds from Baoyuan decoction with myocardial protection activities and their potential targets

保元汤中具有心肌保护作用的活性成分及其潜在作用靶点研究



全 文 :2016
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ActivecompoundsfromBaoyuandecoctionwithmyocardialprotection
activitiesandtheirpotentialtargets
SHUZeliu,ZENGKewu,MAXiaoli,TUPengfei,LIJun,JIANGYong
(StateKeyLaboratoryofNaturalandBiomimeticDrugs,SchoolofPharmaceuticalSciences,Peking
University,Beijing100191,China)
[Abstract] Baoyuandecoction(BYD)isaclassicalChineseformulaforcoronaryheartdiseasewithQideficiency,bloodstasistoni
fyingQiandYangdeficiencyHowever,thechemicalmaterialbasisandunderlyingactionmechanismsofBYDstillacksystemicstu
dyInordertoclarifytheactivecompoundsandthepotentialactionmechanismsofBYD,theoxygenglucosedeprivation/recovery
(OGD/R)inducedH9c2celsinjurymodelswasusedtoscreenthemonomericcompoundsofBYDwithmyocardialprotectionactivity
PubChem′sBioAssaydatabasewasthenusedtoanalyzethepotentialtargetsofactivemonomericcompounds,classifythepredictedbio
logicaltargets,andanalyzetheinternalrelationbetweenactivecompoundsofBYDandbiologicaltargetsThescreeningresultsshowed
thatBYDaqueousextractand17monomericcompoundscouldsignificantlyincreasethesurvivalrateofOGD/RinducedH9c2myocar
dialcelsTheresultsofvirtualtargetsscreeningstudyshowedthat15monomericcompoundsandthepotentialmechanismsformyo
cardialprotectionwererelatedtooxidativestresspathway,calciumionpathway,mitochondrialprotection,antiapoptosis,etc
TheseresultsverifiedthatBYDhadmyocardialprotectionefect,whichwasobtainedbynetworkregulationofmulticomponents
andmultitargetsAltheseresultsprovidethetheoreticalbasisandreferencesfortheclinicalusageofBYDintreatmentofcoro
naryheartdisease
·229·
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[Keywords] Baoyuandecoction(BYD);myocardialprotection;oxygenglucosedeprivationrecoverymodel;activecompounds;po
tentialtargets
doi:10.4268/cjcmm20160527
  
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·329·
2016
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Vol41,No.5 March,2016
ityAnalysis,
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Targets
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31 BYD
Ñ°
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1 
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BYD
Ñ°
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(珋x±s,n=4)
Table1 DiferentconcentrationsofBYDenhancedthecelvia
bilitiesinOGD/Rinjury(珋x±s,n=4)

Ÿ G±
/mg·L-1 ¿jæ°}/%
±Ä
- 9972±110
OGD/R - 5316±3551)
BYD 50 6001±3402)
100 6893±1023)
200 7360±1563)
400 8684±1303)
600 9600±5003)
800 10784±2303)
1000 11866±4373)
  


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1)P<0001;
ªšØ{
(OGD/R)

2)P<
001,3)P<0001。
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$#ö_ñ.o
OGD/R
·vŽ
H9c2
¿
j¬KšØ¼Ž°ÂLM
 
±8
BYD


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±
BYD
$
17
ñóŠÂmBOPSc¿j°ÂŽ#ö_ñ
.¼n
PubChemBioAssay
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<
、10
<_ñ
.¯TU…Qö‡=ŽÚ_ñ.

àBYZ©.°
  ó2 BYD$#ö_ñ.Ï OGD/R·vŽ H9c2¿j¬K
šØ°ÂLM’yË:>Íó
(珋x±s,n=3)
Table2 ThelistofactivecompoundsfromBYDoncelviabili
tiesforthecardiomyocytesexposedtoOGD/Rtreatmentand
theirsources(珋x±s,n=3)
{× _ñ.-³ ¿jæ°}
/%
:>
±Ä
100±021
OGD/R 6169±4041)
1   isomucronulatol7O
βDglucoside
7960±5224)  Astragalusmembran
ceus
2 astragalin 7134±2843) Amembranceus
3 astragalosideⅡ 7238±4012) Amembranceus
4 benzoicacid 7589±1703) Cinnamomumcasia
5   4hydroxytranscin
namicacid
7691±2043) Ccasia
6 fareanol 7640±3363) Ccasia
7 isolariciresinol 7539±5063) Ccasia
8   5methoxyisolaricir
esinol
7501±2693) Ccasia
9  (4carboxyl)phenol
5O( 4 hydroxy
benzoyl )βDapio
furanosyl(l→2)βD
glucopyranoside
7485±3623) Ccasia
10  (+)isolariciresinol
4OβDapiofuranosyl
(1→2)βDglucopyr
anoside
8216±7794) Ccasia
11 protocatechuicaldehyde 13194±22764)Ccasia
12 licuraside 7406±3283) Glycyrhizauralensis
13   7,2′,4′trihydroxy
isoflavan
8633±0974) Guralensis
14   2,4, 4′,βtetra
hydroxydihydrochalcone
8111±0674) Guralensis
15  uralsaponinAdime
thyester
7491±6043) Guralensis
16 20(S)ginsenosideRg2 11869±45104)Panaxginseng
17 cyclo(LLeuLTyr) 7352±5263) Pginseng
  


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1)P<0001;
ªšØ{
(OGD/R)

2)P<
005,3)P<001,4)P<0001。
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ÌS
15
ñ_ñ.M-=‰‡§’yÌ

10
X!ªFS?°±YZŽÉÊpq¼nÍ
ó

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3。
4 
À
FS?ɯŒßٕÜݑ©Ž¬wT?

m?}•*y¼°

-´þ`_±

éFS?0
2]‘á

Sc\¯‘ScdƇ«¶¬K
(myo
cardialischemiareperfusioninjury,MIRI)
«FS?
š›ÇïxŽ?€

-
MIRI
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ó
3 BYD
$°Â#ö_ñ.noÉÊp–Íó
Table3 ThepotentialtargetslistofactivecompoundsfromBYD
_ñ. nopq
isomucronulatol7OβDglucoside polyphenoloxidase2
 chainB,thestructureofwildtypehumanhadh2(17βhydroxysteroiddehydrogenasetype10)boundto
Nad+at12A
 chainA,thestructureofwildtypehumanhadh2(17βhydroxysteroiddehydrogenasetype10)boundto
Nad+at12A
FADlinkedsulfhydryloxidaseALR
placentagrowthfactor
vascularendothelialgrowthfactorA
astragalin DNApolymerasekappa
aldosereductase
FADlinkedsulfhydryloxidaseALR
prolyl4hydroxylase,betapolypeptide
chainA,crystalstructureofthehuman2oxoglutarateoxygenaseloc390245
DNApolymeraseiota
dualspecificitytyrosinephosphorylationregulatedkinase1A
DNApolymerasebeta
astragalosideⅡ tyrosinase
orexinreceptortype1
nuclearreceptorRORgammaisoform1
chainA,humanbcl2incomplexwithbimbh3peptide
DNAdamageinducibletranscript3protein
nuclearreceptorRORgamma
benzoicacid nuclearfactorerythroid2relatedfactor2isoform1
carbonicanhydrase2
peroxisomeproliferatoractivatedreceptorgamma
vitaminD3receptorisoformVDRA
4hydroxytranscinnamicacid carbonicanhydrase2
carbonicanhydrase1
carbonicanhydrase9
carbonicanhydrase14
carbonicanhydrase12
carbonicanhydrase7
aldosereductase
aldoketoreductasefamily1memberB10
aldehydedehydrogenase1family,memberA1
fareanol calmodulin
isolariciresinol plateletactivatingfactoracetylhydrolaseIBsubunitbetaisoformb
arachidonate12lipoxygenase,12Stype
carbonicanhydrase
5methoxyisolariciresinol plateletactivatingfactoracetylhydrolaseprecursor
plasminogenprecursor
troponinⅠ,cardiacmuscle
protocatechuicaldehyde chainA,crystalstructureofthehuman2oxoglutarateoxygenaseloc390245
4aminobutyrateaminotransferase,mitochondrial
FADlinkedsulfhydryloxidaseALR
succinatesemialdehydedehydrogenase,mitochondrial
licuraside FADlinkedsulfhydryloxidaseALR
prolyl4hydroxylase,betapolypeptide
DNApolymerasekappa
dualspecificitytyrosinephosphorylationregulatedkinase1A
·529·
2016
y

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41
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}
Vol41,No.5 March,2016
Âó

_ñ. nopq
sodium/glucosecotransporter1
aldosereductase
DNApolymeraseiota
7,2′,4′trihydroxyisoflavan salidase
estrogenreceptorbeta
estrogenreceptor
tyrosineproteinphosphatasenonreceptortype1
estrogenreceptor
potassiumvoltagegatedchannelsubfamilyKQTmember2
polyphenoloxidase2
Smad3
2,4,4′,βtetrahydroxydihydrochalcone cytochromeP4503A4isoform1
Aldosereductase
estrogennuclearreceptoralpha
cytochromeP4502C19precursor
tyrosineproteinphosphatasenonreceptortype1
plateletactivatingfactoracetylhydrolaseIBsubunitbetaisoformb
celulartumorantigenp53
ARprotein
microtubuleassociatedproteintau
uralsaponinAdimethyester corticotropinreleasinghormonereceptor2
microphthalmiaassociatedtranscriptionfactorisoform1
nuclearfactorNFkappaBp105subunitisoform1
20(S)ginsenosideRg2 sodiumchannelproteintype10subunitalpha
nuclearfactorNFkappaBp105subunitisoform1
glycogensynthasekinase3beta
vasopressinV1areceptor
Cyclo(LLeuLTyr) mutypeopioidreceptor
deltatypeopioidreceptor
glutamatereceptor1
glutamatereceptor2
glutamatereceptor4
glutamatereceptor3
kappatypeopioidreceptor
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