Lysiphyllum strychnifolium (Craib) A. Schmitz Extracts Moderate the Expression of Drug-Metabolizing Enzymes: In Vivo Study to Clinical Propose
PHARMACEUTICALS(2023)
摘要
Lysiphyllum strychnifolium (Craib) A. Schmitz (LS) has been traditionally used as a medicinal herb by folk healers in Thailand with rare evidence-based support. Hepatic cytochrome P450s (CYPs450) are well known as the drug-metabolizing enzymes that catalyze all drugs and toxicants. In this study, we investigated the mRNA levels of six clinically important CYPs450, i.e., CYP1A2, 3A2, 2C11, 2D1, 2D2, and 2E1, in rats given LS extracts. Seventy Wistar rats were randomized into seven groups (n = 10). Each group was given LS stem ethanol (SE) and leaf water (LW) extracts orally at doses of 300, 2000, and 5000 mg/kg body weight (mg/kg.bw) for twenty-eight consecutive days. After treatment, the expression of CYPs450 genes was measured using quantitative real-time PCR. The results revealed that SE and LW, which contained quercetin and gallic acid, promoted the upregulation of all CYPs450. Almost all CYPs450 genes were downregulated in all male LW-treated rats but upregulated in female-treated groups, suggesting that CYP gene expressions in LS-treated rats were influenced by gender. Moderate and high doses of the LS extracts had a tendency to induce six CYP450s' transcription levels in both rat genders. CYP2E1 gene showed a unique expression level in male rats receiving SE at a dose of 2000 mg/kg.bw, whereas a low dose of 300 mg/kg.bw was found in the LW-treated female group. As a result, our findings suggest that different doses of LS extracts can moderate the varying mRNA expression of clinically relevant CYP genes. In this study, we provide information about CYP induction and inhibition in vivo, which could be a desirable condition for furthering the practical use of LS extracts in humans.
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关键词
alcohol detoxification,cytochrome P450,CYP induction,CYP inhibition,Lysiphyllum strychnifolium
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