Metabolic Fingerprint and Effects of Aconite Alkaloid Components on the Activities of CYP450 Isozymes in Rat Liver Microsomes

doi:10.7503/cjcu20130492

Abstract

Abstract:

The effects of the components of monoester and diester diterpenoid alkaloids(MDAs, DDAs) on the activities of hepatic microsomal CYP450 isozymes(CYP1A2, CYP2C, CYP2E1, CYP2D, CYP3A) were studied by ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) combined with cocktail probe substrate' s method. The metabolic fingerprints of MDAs and DDAs' components were studied in rat liver microsomes using UPLC-Q-TOF/MS/MS. The results showed that the components of MDAs had strong inhibitory effects on the activities of CYP2C and 2D, the IC₅₀ value was 7.44 and 6.74 μmol/L, respectively. The components of DDAs had weaker inhibitory effects on the activities of CYP1A2, 3A, 2C and 2D, the IC₅₀ value was 39.48, 70.44, 17.36 and 86.04 μmol/L, respectively. Six metabolites of DDAs in rat liver microsomes were identified using UPLC-Q-TOF-MS/MS. They can be used as marked peaks for metabolic fingerprint of aconite alkaloids components.

Key words: Aconite alkaloid, Cytochrome P450, Metabolic fingerprint, Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), Cocktail probe substrate

CLC Number:

O657.6

TrendMD:

BI Yun-Feng, LIU Shu, LI Xue, LIU Zhi-Qiang, SONG Feng-Rui. Metabolic Fingerprint and Effects of Aconite Alkaloid Components on the Activities of CYP450 Isozymes in Rat Liver Microsomes[J]. Chem. J. Chinese Universities, 2013, 34(9): 2084.

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