In vitro inhibitory effects of dihydromyricetin on human liver cytochrome P450 enzymes

Autor: Xiaohua Li, Lu Liu, Sen Sun, Hongbing Rui
Jazyk: angličtina
Rok vydání: 2017
Předmět:
CYP2D6
Flavonols
ved/biology.organism_classification_rank.species
Pharmaceutical Science
Pharmacology
Binding
Competitive
030226 pharmacology & pharmacy
Antioxidants
cyp2e1
03 medical and health sciences
0302 clinical medicine
Cytochrome P-450 CYP2D6 Inhibitors
Drug Discovery
cyp3a4
Cytochrome P-450 CYP3A
Humans
chemistry.chemical_classification
biology
CYP3A4
ved/biology
Anti-Inflammatory Agents
Non-Steroidal
lcsh:RM1-950
Cytochrome P450
Cytochrome P-450 CYP2E1
General Medicine
CYP2E1
Antineoplastic Agents
Phytogenic
In vitro
Cytochrome P-450 CYP2E1 Inhibitors
cyp2d6
Kinetics
Enzyme
lcsh:Therapeutics. Pharmacology
Cytochrome P-450 CYP2D6
Complementary and alternative medicine
Biochemistry
chemistry
herb–drug interaction
030220 oncology & carcinogenesis
ampelopsis grossedentata
Microsomes
Liver
biology.protein
Microsome
Cytochrome P-450 CYP3A Inhibitors
Molecular Medicine
Ampelopsis grossedentata
Research Article
Zdroj: Pharmaceutical Biology, Vol 55, Iss 1, Pp 1868-1874 (2017)
Pharmaceutical Biology
ISSN: 1744-5116
1388-0209
Popis: Context: Dihydromyricetin (DHM) is the most abundant and active flavonoid component isolated from Ampelopsis grossedentata (Hand-Mazz) W.T. Wang (Vitaceae) and it possesses numerous pharmacological activities. However, whether DHM affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Materials and methods: The inhibitory effects of DHM on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs). Results: The results showed that DHM could inhibit the activity of CYP3A4, CYP2E1 and CYP2D6, with IC50 values of 14.75, 25.74 and 22.69 μM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that DHM was not only a non-competitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2E1 and CYP2D6, with Ki values of 6.06, 9.24 and 10.52 μM, respectively. In addition, DHM is a time-dependent inhibitor for CYP3A4 with KI/Kinact value of 12.17/0.057 min−1 μM−1. Discussion and conclusion: The in vitro studies of DHM with CYP isoforms indicate that DHM has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2D6. Further clinical studies are needed to evaluate the significance of this interaction.
Databáze: OpenAIRE
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