Two Approaches for Evaluating the Effects of Galangin on the Activities and mRNA Expression of Seven CYP450.
Molecules
; 24(6)2019 Mar 25.
Article
em En
| MEDLINE
| ID: mdl-30934565
ABSTRACT
Galangin is a marker compound of honey and Alpinia officinarum Hance that exhibits great potential for anti-microbial, anti-diabetic, anti-obesity, anti-tumour and anti-inflammatory applications. Galangin is frequently consumed in combination with common clinical drugs. Here, we evaluated the effects of galangin on cytochrome P450 (CYP)-mediated metabolism, using two different approaches, to predict drugâ»drug interactions. Male Sprague Dawley rats were administered galangin daily for 8 weeks. A "cocktail-probes" approach was employed to evaluate the activities of different CYP450 enzymes. Blood samples of seven probe drugs were analysed using liquid chromatography-tandem mass spectrometry in positive and negative electrospray-ionisation modes. Pharmacokinetic parameters were calculated to identify statistical differences. CYP mRNA-expression levels were investigated in real-time quantitative polymerase chain reaction experiments. The galangin-treated group showed significantly decreased AUC0â»∞ and Cmax values for CYP1A2, and CYP2B3. The galangin-treated group showed significantly increased AUC0â»∞ and Cmax values for CYP2C13 and CYP3A1. No significant influences were observed in the pharmacokinetic profiles of CYP2C11, CYP2D4 and CYP2E1. The mRNA-expression results were consistent with the pharmacokinetic results. Thus, CYP450 enzyme activities may be altered by long-term galangin administration, suggesting galangin to be a promising candidate molecule for enhancing oral drug bioavailability and chemoprevention and reversing multidrug resistance.
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Base de dados:
MEDLINE
Assunto principal:
Flavonoides
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RNA Mensageiro
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Regulação da Expressão Gênica
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Sistema Enzimático do Citocromo P-450
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article