Evidence-Based Complementary and Alternative Medicine

Review Article

In Vivo and In Vitro Metabolites from the Main Diester and Monoester Diterpenoid Alkaloids in a Traditional Chinese Herb, the Aconitum Species

Table 5

Metabolites of DDAs and MDAs converted in the liver.
Alkaloids (ESI+)FormulaIdentification Involved CYP450sMetabolic procedureMS detectionReferences
AC662C34H47NO12Hydroxy ACCYP3A5, CYP2D6Human; liver microsomes and recombinant CYP450s; incubation, in vitro.Q-TOF[35] (M6)
NAaRats; liver microsome S9 fraction; incubation, in vitro.IT[36] (M5)
Guinea pigs and mice; liver microsomes; incubation, in vitro.HRMS, MS2[37] (M6)
644C34H45NO113-Dehydrogen ACCYP3A4, CYP3A5Human; liver microsomes and recombinant CYP450s; incubation, in vitro.Q-TOF[35] (M5)
NAGuinea pigs and mice; liver microsomes; incubation, in vitro.HRMS, MS2[37] (M5)
Dehydrogen ACCYP3A, CYP1A1/2 Rats; liver microsomes; incubation, in vitro.IT[4] (M6)
NARats; liver microsome S9 fraction; incubation, in vitro.IT[36] (M7)
632C33H45NO1116-O-Demethyl ACCYP3A, CYP1A1/2 Rats; liver microsomes; incubation, in vitro.IT[4] (M2)
CYP3A4, CYP3A5, CYP2D6, CYP2C9Human; liver microsomes and recombinant CYP450s; incubation, in vitro.Q-TOF[35] (M2)
NARats; liver microsome S9 fraction; incubation, in vitro.IT[36] (M6)
NAGuinea pigs and mice; liver microsomes; incubation, in vitro.HRMS, MS2[37] (M2)
O-Demethyl ACCYP3A, CYP1A1/2 Rats; liver microsomes; incubation, in vitro.IT[4] (M1)
CYP3A4, CYP3A5, CYP2C8, CYP2D6Human; liver microsomes and recombinant CYP450s; incubation, in vitro.Q-TOF[35] (M1)
NAGuinea pigs and mice; liver microsomes; incubation, in vitro.HRMS, MS2[37] (M1)
630C34H47NO10Deoxyaconitine (3-deoxy AC)NAGuinea pigs and mice; liver microsomes; incubation, in vitro.HRMS, MS2[37] (M7)
Deoxy ACNARats; liver microsome S9 fraction; incubation, in vitro.IT[36] (M8)
618C32H43NO11O-Didemethyl ACCYP3A, CYP1A1/2 Rats; liver microsomes; incubation, in vitro.IT[4] (M3)
CYP2D6, CYP3A5Human; liver microsomes and recombinant CYP450s; incubation, in vitro.Q-TOF[35] (M4)
NARats; liver microsome S9 fraction; incubation, in vitro.IT[36] (M4)
NAGuinea pigs and mice; liver microsomes; incubation, in vitro.HRMS, MS2[37] (M3)
N-Deethyl ACCYP3A, CYP1A1/2Rats; liver microsomes; incubation, in vitro.IT[4] (M4)
CYP3A4, CYP3A5, CYP2D6, CYP2C9Human; liver microsomes and recombinant CYP450s; incubation, in vitro.Q-TOF[35] (M3)
NARats; liver microsomes; incubation, in vitro. Q-TOF[38] (M4)
NARats; liver microsome S9 fraction; incubation, in vitro.IT[36] (M2)
NAGuinea pigs and mice; liver microsomes; incubation, in vitro.HRMS, MS2[37] (M4)
604C32H45NO10BACCYP3A, CYP1A1/2Rats; liver microsomes; incubation, in vitro.IT[4] (M5)
NARats; liver microsome and S9 fraction; incubation, in vitro.Q-Trap[39]
NARats; liver microsomes; incubation, in vitro. Q-TOF[38] (M2)
NARats; liver microsome S9 fraction; incubation, in vitro.IT[36] (M1)
NAGuinea pigs and mice; liver microsomes; incubation, in vitro.HRMS, MS2[37] (M8)
586C32H43NO9Deacetoxy ACbNARats; liver microsome S9 fraction; incubation, in vitro.IT[36] (M3)
482C25H39NO8Dehydrated aconineNARabbits; liver; ig, in vivo. IT[40]
MA648C33H45NO12Hydroxy MACYP3A4, CYP3A5Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[41] (M5)
2-Hydroxy MANARats; liver microsomes; incubation, in vitro. Q-TOF, QQQ[38] (M5)
CYP3A, CYP2C, CYP2DRats; liver microsomes; incubation, in vitro. QQQ; IM[42] (M5)
630C33H43NO11Dehydrogen MACYP3A4, CYP3A5Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[41] (M4)
NARats; liver microsomes; incubation, in vitro. Q-TOF, QQQ[38] (M6)
3-Dehydrogen MACYP3A, CYP2DRats; liver microsomes; incubation, in vitro. QQQ; IM[42] (M2)
618C32H43NO1116-O-Demethyl MA CYP2C8, CYP3A4, CYP3A5Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[41] (M2)
CYP3ARats; liver microsomes; incubation, in vitro. QQQ; IM[42] (M4)
1-O-Demethyl MACYP3A, CYP2CRats; liver microsomes; incubation, in vitro. QQQ; IM[42] (M3)
18-O-Demethyl MACYP3A, CYP2CRats; liver microsomes; incubation, in vitro. QQQ; IM[42] (M6)
Demethyl MACYP2C8, CYP2D6, CYP3A5Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[41] (M1)
Demethyl MACYP3A4, CYP3A5Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[41] (M3)
616C32H41NO11Demethyl-dehydrogen MACYP3A4, CYP3A5Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[41] (M6)
Demethyl-dehydrogen MACYP2C8, CYP3A4, CYP3A5Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[41] (M7, M8)
Demethyl-dehydrogen MACYP2C8, CYP2C9, CYP2D6, CYP3A4, CYP3A5Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[41] (M9)
590C31H44NO10BMANARats; liver microsome and S9 fraction; incubation, in vitro.Q-Trap[39]
NARats; liver microsomes; incubation, in vitro. Q-TOF, QQQ[38] (M1)
HA632C33H45NO11MACYP3A4, CYP3A5, CYP2C19, CYP2D6, CYP2E1Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[43] (M8)
CYP3A, CYP2D, CYP2C, CYP2E1Rats; liver microsomes; incubation, in vitro. QQQ[44] (M6)
2-Hydroxy HACYP3A, CYP2C, CYP2D, CYP1A2Rats; liver microsomes; incubation, in vitro. QQQ[44] (M4)
Hydroxy HACYP3A4, CYP3A5, CYP2C19, CYP2D6, CYP2E1Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[43] (M7)
614C33H43NO1015-Dehydrogen HACYP3A, CYP2D, CYP2E1Rats; liver microsomes; incubation, in vitro. QQQ[44] (M2)
602C32H43NO1016-O-Demethyl HACYP3A4, CYP3A5, CYP2C19, CYP2D6, CYP2E1Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[43] (M2)
1-O-Demethyl HACYP3A, CYP2D, CYP2CRats; liver microsomes; incubation, in vitro. QQQ[44] (M5)
18-O-Demethyl HACYP3A, CYP2CRats; liver microsomes; incubation, in vitro. QQQ[44] (M7)
Demethyl HACYP3A4, CYP3A5, CYP2C8, CYP2C19, CYP2D6, CYP2E1Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[43] (M1)
Demethyl HACYP3A4, CYP3A5, CYP1A2, CYP2C8, CYP2C19, CYP2D6, CYP2E1Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[43] (M3)
600C32H41NO10Demethyl-dehydrogen HACYP3A4, CYP3A5, CYP2C19, CYP2D6, CYP2E1Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[43] (M4–M6)
590C31H43NO102-Hydroxy BHACYP3A, CYP2CRats; liver microsomes; incubation, in vitro. QQQ[44] (M1)
588C31H41NO10Didemethyl HACYP3A4, CYP3A5, CYP2C19, CYP2D6, CYP2E1Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[43]
(M9, M10)
Didemethyl HACYP3A4, CYP3A5, CYP2C19Human (male); liver microsomes and recombinant CYP450s;
incubation, in vitro.		Q-TOF[43] (M11)
574C31H43NO9BHACYP3A, CYP2DRats; liver microsomes; incubation, in vitro. QQQ[44] (M3)
NARats; liver microsomes; incubation, in vitro. Q-TOF, QQQ[38] (M3)
NARats; liver microsome and S9 fraction; incubation, in vitro.Q-Trap[39]
BAC602C32H43NO10Dehydrogen BAC (M1, M2)CYP3A4, CYP3A5Human; liver microsomes;
incubation, in vitro.		Q-TOF [45]
590C31H43NO10Demethyl BAC (M5)CYP3A4, CYP3A5, CYP2D6
Demethyl BAC (M6)CYP3A4, CYP3A5
588C31H41NO10Demethyl-dehydrogen BAC (M3)CYP3A4, CYP3A5
576C30H41NO10Deethyl BAC or
didemethyl BAC (M7)		CYP3A4, CYP3A5
574C30H39NO10Didemethyl-dehydrogen BAC or
deethyl-dehydrogen BAC (M4)		CYP3A4, CYP3A5
BMA606C31H43NO11Hydroxy BMA (M8)CYP3A4, CYP3A5Human; liver microsomes;
incubation, in vitro.		Q-TOF [45]
588C31H41NO10Dehydrogen BMA (M1, M2)CYP3A4, CYP3A5
576C30H41NO10Demethyl BMA (M5)CYP3A4, CYP3A5, CYP2D6, CYP2C8
Demethyl BMA (M6, M7)CYP3A4, CYP3A5
574C30H39NO10Demethyl-dehydrogen BMA (M3, M4)CYP3A4, CYP3A5
BHA590C31H43NO10Hydroxy BHA (M7)CYP3A4, CYP3A5Human; liver microsomes;
incubation, in vitro.		Q-TOF [45]
BMA (M8)CYP3A4, CYP3A5
572C31H41NO9Dehydrogen BHA (M1, M2)CYP3A4, CYP3A5
560C30H41NO9Demethyl BHA (M5)CYP3A4
Demethyl BHA (M4, M6)CYP3A4, CYP3A5
558C30H39NO9Demethyl-dehydrogen BHA (M3)CYP3A4, CYP3A5
556C30H37NO9Demethyl-didehydrogen BHA (M9)CYP3A4, CYP3A5
Not available.
bDeacetoxy aconitine may also be referred to as pyroaconitine in the literature.