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Screening and identification of DPP-4 inhibitors from Xiaokean formula by a fluorescent probe

基于荧光探针的消渴安中DPP-4抑制剂的筛选与鉴定



全 文 :2016
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Vol41,No.7 April,2016

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ScreeningandidentificationofDPP4inhibitorsfromXiaokean
formulabyafluorescentprobe
WUXueli1,WANGYi2,ZHAOXiaoping1
(1.ZhejiangChineseMedicalUniversity,Hangzhou310053,China;
2.ColegeofPharmaceuticalSciences,ZhejiangUniversity,Hangzhou310058,China)
[Abstract] Fluorescentbioprobeshaveatractedincreasingatentionsinstudiesforscreeningbioactivecompoundsfromtraditional
ChinesemedicinesInthisstudy,anewtypefluorescentprobewiththefunctionofaggregationinducedemission(AIE)wasusedto
screendipeptidylpeptidase4(DPP4)inhibitorfromXiaokeanformula,whichhasbeenclinicalyusedforthetreatmentoftype2dia
betesmelitusPotentialDPP4inhibitorswerescreenedbythefluorescentprobe,withdiprotinAasthepositivecontrol;totaly43
componentswereisolatedfromXiaokeanformulabysystematicseparationTheresultsshowedthat13componentscanexertinhibitory
efectsonDPP4activity;16compoundswerefurtheridentifiedbyliquidchromatographymassspectrometry(LCMS)fromthoseac
tivecomponentsTheinhibitoryefectsof14compoundswerefurtherverified,whilefiveofthemshowedsignificantinhibitionagainst
DPP4SalvianolicacidC,ginsenosideRg5andtimosaponinAIinhibitedDPP4activityattheconcentrationof550μmol·L
-1ina
dosedependentmannerThus,ourstudyprovidedasuccessfulexampleforscreeningbioactivecompoundsfromtraditionalChinese
medicinesbyusinganovelfluorescentprobe
[Keywords] DPP4inhibitor;Xiaokeanformula;type2diabetesmelitus;aggregationinducedemission;fluorescentprobe
doi:10.4268/cjcmm20160714
  
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(9557±246)%,(9012±530)%,(5573±
177)%,(5361±838)%,(4515±683)%,
Ó$
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5~50μmol·L-1-BÕ÷±ßÉ9ˁÅ,]q3。
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·3421·
2016
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Vol41,No.7 April,2016
*
1 
ðµ—$L/_V˜_vâ
Table1 ChemicalinformationofchemicalsinactivecomponentsidentifiedbyLCMS
No tR/min 삗 Þçvâ _V˜
1 3870 B02,B03  9653915[M+HCOOH-H]-,9196968[M-H]-,
9036226[M-H2O+H]+
»éê
BⅡ
2 4512 B03  9634711[M+HCOOH-H]-,9177433[M-H]-,
9035342[M-H2O+H]+,9195696[M+H]+
¥»éê
BⅡ
3 5808 B03  9474310[M+HCOOH-H]-,9017074[M-H]-,
9036105[M+H]+
»éê

4 6142 B03,C07,C08,C13,C15,C17,C18,C19,C20,C21 11535962[M+HCOOH-H]-,11088174[M-H]- $ÝéêRb1
5 6324 B03,C13,C15,C17,C18,C19,C20,C21 11235479[M+HCOOH-H]-,10785400[M-H]- $ÝéêRc
6 6488 B03 9556736[M-H]- $ÝéêRo
7 6798 B03,C05,C06,C15,C17,C18,C19,C20,C21 9914966[M+HCOOH-H]-,9457754[M-H]- $ÝéêRd
8 6822 B03,C05,C06,C07,C08  8034009[M+HCOOH-H]
-,7576829[M-H]-,
7416418[M-H2O+H]+
»éêⅠ
9 7448 B03,C08  7853843[M+HCOOH-H]-,7396975[M-H]-,
7585765[M+NH3+H]+,7415608[M+H]+
»éê
AⅢ
10 4158  B02,B03,C05,C06,C07,C08,C15,C17,C18,
C19,C20,C21
3363589[M]+ *:½¾
11 4314  B02,B03,C05,C06,C07,C08,C13,C15,C17,
C18,C19,C20,C21
3203525[M]+ ÀÁ¾
12 4976  B02,B03,C05,C06,C07,C08,C13,C15,C17,
C18,C19,C20,C21
3523105[M]+ nRã
13 5188  B02,B03,C05,C06,C07,C08,C13,C15,C17,
C18,C19,C20,C21
3362755[M]+ :½¾
14 6938 C07 5795626[M+H]+ »éêAⅠ
15 7133 C08 4743612[M-H2O+H]+ Ü¢¼C
16 7721 C13  8116062[M+HCOOH-H]-,7658474[M-H]-,
7683213[M+H]+
$Ýéê
Rg5
  
å


1~9
dÒOþϕ
B03
ZžïGq


10~14
dÒOþϕ
C07
?žïGq


15,16
dÒOþ—`ϕ
C08
?žïGq¬
C13
ZžïGq

q
3 3
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Fig3 Dosedependentinhibitionof3compoundsonDPP4
  
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Q£îO
920
¨…†Ñ烫¬
[J].
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,2005,21(1):
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{Î(

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,2010,26
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