Involvement of CYP3A4/5 and CYP2D6 in the metabolism of aconitine using human liver microsomes and recombinant CYP450 enzymes (Record no. 48682)

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control field MX-MdCICY
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control field 20250625153942.0
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Transcribing agency CICY
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Classification number (OCLC) (R) ; Classification number, CALL (RLIN) (NR) B-14494
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Title Involvement of CYP3A4/5 and CYP2D6 in the metabolism of aconitine using human liver microsomes and recombinant CYP450 enzymes
490 0# - SERIES STATEMENT
Volume/sequential designation Toxicology Letters, 202(1), p.47-54, 2011
520 3# - SUMMARY, ETC.
Summary, etc. Aconitine (AC), a famous major Aconitum alkaloid, has effective antirheumatic function with high toxicity. The aim of our study was to in-depth investigate cytochrome P450 isozymes (CYPs)involved in aconitine metabolism in vitro.We used human liver microsomes (HLMs)as well as recombinant CYPs to investigate the metabolism pathways of aconitine by liquid chromatography-tandem mass spectrometry. Fluvoxamine maleate, gemfibrozil, amiodarone hydrochloride, omeprazole, quinidine, diethyldithiocarbamic acid and ketoconazole were successfully applied as test inhibitors for CYP1A2, CYP2C8, CYP2C9, CYP2C19*1, CYP2D6*1, CYP2E1 and CYP3A4/5 in HLMs, respectively. Six CYP-mediated metabolites were found and characterized in human liver microsomes and eight recombinant CYP isoforms. The inhibitor of CYP 3A had a strong inhibitory effect, the inhibitors of CYP 2C9, 2C8 and CYP2D6 had little inhibitory effects, whereas CYP2C19, 1A2 and 2E1 had no obvious inhibitory effects on AC metabolism. Hydroxylation and di-demethylation of aconitine were conducted by human recombinant CYP 3A5 and 2D6, dehydrogenation was only processed by CYP3A4/5, and the main CYP isoforms metabolizing aconitine to demethyl-aconitine and N-deethyl-aconitine were CYP3A4/5 and CYP2D6. In conclusion, aconitine can be transformed into at least six CYP-mediated metabolites in HLMs, CYP 3A4/5 and 2D6 were the most important CYP isoforms responsible for the de-methylation, N-deethylation, dehydrogenation, and hydroxylation of aconitine.
650 14 - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element ACONITINE
650 14 - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element CYTOCHROME P450
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Topical term or geographic name entry element METABOLISM
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Topical term or geographic name entry element MICROSOMES
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Topical term or geographic name entry element LC-MS/MS
700 12 - ADDED ENTRY--PERSONAL NAME
Personal name Lan Tang
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Personal name Ling Ye
700 12 - ADDED ENTRY--PERSONAL NAME
Personal name Chang Lv
700 12 - ADDED ENTRY--PERSONAL NAME
Personal name Zhijie Zheng
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Personal name Yun Gong
700 12 - ADDED ENTRY--PERSONAL NAME
Personal name Zhongqiu Liu
856 40 - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="https://drive.google.com/file/d/1ZDel4KGZn0LpvMK4Um2xeQdkqpR7wuwo/view?usp=drivesdk">https://drive.google.com/file/d/1ZDel4KGZn0LpvMK4Um2xeQdkqpR7wuwo/view?usp=drivesdk</a>
Public note Para ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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Source of classification or shelving scheme Clasificación local
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  Clasificación local     Ref1 CICY CICY Documento préstamo interbibliotecario 25.06.2025   B-14494 25.06.2025 25.06.2025 Documentos solicitados