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Effects of aqueous extract of Cassiae Semen on activity hepatic microsomal CYP450 isozymes in rats

决明子水提液对大鼠肝脏CYP450酶的影响



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EfectsofaqueousextractofCassiaeSemenonactivityhepatic
microsomalCYP450isozymesinrats
XULonglong1,2,TANGXianglin1,2,MAZengchun2,WANGYuguang2,LIANGQiande2,
TANHongling2,XIAOChengrong2,LIHua3,YUANMei3,GAOYue1,2
(1.GraduateSchoolofAnhuiMedicalUniversity,Hefei230032,China;
2.InstituteofRadiationMedicineScience,AcademyofMilitaryMedicalSciences,Beijing100850,China;
3.InstituteofToxicologyandPharmacology,AcademyofMilitaryMedicalSciences,Beijing100850,China)
[Abstract] TostudytheefectofaqueousextractofCassiaeSemenontheactivity,mRNAandproteinexpressionsofcytochrome
P450(CYP450)systeminratlivermicrosomes,microsomesofratliverwerepreparedaftertheoraladministrationwithaqueousextract
ofCassiaeSemenfor14daysTheenzymeactivitywasquantifiedbyCocktailmethodMeanwhile,themRNAandproteinexpressions
ofCYP1A2,CYP2B1,CYP2C11,CYP2D2,CYP2E1andCYP3A1intheliversweredetectedbyRTPCRandWesternblotThere
sultofthisexperimentwasthataqueousextractofCassiaeSemenobviouslyinducedtheenzymeactivitiesofCYP1A2,CYP2B1,
CYP2C11,CYP2D2,CYP2E1andCYP3A1LowdoseofaqueousextractofCassiaeSemensignificantlyreducedtheactivityof
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CYP2D2,buttheactivityofCYP2D2wassignificantlyinducedbymiddledoseandhighdoseofaqueousextractofCassiaeSemen
ThesesubtypeswereincreasedinadosedependentmannerexceptforCYP3A1ThemRNAlevelsofCYP1A2,CYP2C11,CYP2D2
andCYP2E1werealsoinducedinratstreatedwithaqueousextractofCassiaeSemen,butwithnosignificantefectinCYP2B1and
CYP3A1mRNAexpressionsTheproteinlevelsofCYP2C11andCYP2E1werealsoinducedinratstreatedwithaqueousextractof
CassiaeSemen,butwithnosignificantdiferenceSincetheenzymeactivity,mRNAandproteinexpressionsofCYP450,particularly
CYP2C11and2E1subtypes,wereinducedorinhibitedbyaqueousextractofCassiaeSementovaringdegrees,suggestingthepotential
drugdruginteractionsshouldbeconcerned
[Keywords] CassiaeSemen;cytochromeP450;Cocktailprobemethod;QPCR;Westernblot
doi:10.4268/cjcmm20160823
  
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CYP1A2 CGCCCAGAGCGGTTTCTTA TCCCAAGCCGAAGAGCATC
CYP2B1 ACCGGCTACCAACCCTTGAT TGTGTGGTACTCCAATAGGGACAA
CYP2C11 CTGCTGCTGCTGAAACACGTG GGATGACAGCGTACTATCAC
CYP2D2 GTGGCGAGAGCAGAGACGATTC ACGAGCATAAACAAGGGAGGCAAT
CYP2E1 CTCCTCGTCATATCCATCTG GCAGCCAATCAGAAATGTGG
CYP3A1 GCTAGAGGGACAACACAGAGGAGT TAGAGGAGCACCAGGACGACTG
GAPDH CAAGGTCATCCATGACAACTTTG GGGCCATCCACAGTCTTCTG
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  +3 €-‚ŸP¶o·Á4³mxë\q̹ÄÂÃ(珋x±s,n=5)
Table3 EfectsofaqueousextractofCassiaeSemenontheactivityofhepaticmicrosomalCYP450isozymesinrats(珋x±s,n=5)
nmol·min-1·g-1
´e
CYP1A2 CYP2B1 CYP2C11 CYP2D2 CYP2E1 CYP3A1
$0
   117121±21976 152230±26281 92040±22102 207122±20749 604775±77611 258824±16512
åm•ð
190151±335782) 198019±359992) 348793±617612) 129370±146582) 3214660±1335112) 292760±333241)
±„õ
  101770±8770 144051±19067 82514±19326 181928±324361) 682338±128652 371030±335282)
$„õ
  141663±165601) 186859±209182) 126786±216481) 285803±280172) 1087004±1107882) 339603±348582)
O„õ
  192735±159562) 218883±199622) 190022±202512) 330600±257312) 1820829±1877902) 379897±151842)
  
g

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q

U
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Fig1 EfectsofaqueousextractofCassiaeSemenonthemR
NArelativeexpressionofhepaticmicrosomalCYP450isozymes
inrats(珋x±s,n=3)
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Fig2 EfectsofaqueousextractofCassiaeSemenontheproteinrelativeexpressionofhepaticmicrosomalCYP2C11,2E1inrats(珋x±
s,n=3)
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