槲皮素作为外源性物质代谢的调节剂：整合CYP450调控、II相结合通路及转运体介导的药物相互作用。
完整摘要 · 中文译文
目的：槲皮素是膳食中含量最丰富的黄酮类化合物之一，因其能够通过抑制和调节药物代谢酶及膜转运体来调控外源性物质代谢而引起了广泛关注。然而，由于现有证据较为零散且主要来自临床前研究，这些相互作用的临床相关性仍不明确。本系统综述批判性地评估槲皮素对人类I相细胞色素P450酶、II相结合途径、药物转运体以及有临床意义的药代动力学药物相互作用的影响。 方法：按照PRISMA 2020指南，在PubMed/MEDLINE、Scopus、Web of Science、Embase和Google Scholar中进行了系统性文献检索。我们识别并批判性地综合了研究槲皮素介导的外源性物质代谢调节的原始研究，优先纳入人体机制研究、人体药代动力学研究以及有临床记录证据的药物相互作用。 结果：现有证据表明，槲皮素可调节多种CYP450亚型、II相酶以及主要药物转运体，包括P-糖蛋白、乳腺癌耐药蛋白和有机阴离子转运多肽。然而，仅在少数底物中证实了具有临床意义的药代动力学相互作用，主要涉及CYP2C9、CYP2E1和P-糖蛋白，而许多经实验预测的相互作用并未在人体中转化为有临床意义的影响。现有证据进一步强调 广泛的II相代谢、循环结合型代谢物、转运体-酶相互作用以及剂量依赖性全身暴露在决定相互作用风险中的重要性。 结论：现有证据支持槲皮素介导药物相互作用的生物学合理性，但表明其临床意义具有底物依赖性，且对于大多数治疗药物而言仍缺乏充分表征。需要设计良好的人体药代动力学研究，采用标准化的槲皮素制剂、经过验证的探针底物、定量药代动力学终点以及药物遗传学方法，以建立槲皮素与常规药物安全合用的循证建议。
完整摘要 · 英文原文
PURPOSE: Quercetin is one of the most abundant dietary flavonoids and has attracted considerable interest because it can modulate xenobiotic metabolism by inhibiting and regulating drug-metabolizing enzymes and membrane transporters. However, the clinical relevance of these interactions remains uncertain because available evidence is fragmented and largely derived from preclinical studies. This systematic review critically evaluates quercetin's effects on human phase I cytochrome P450 enzymes, phase II conjugation pathways, drug transporters, and clinically relevant pharmacokinetic drug interactions. METHODS: A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, Embase, and Google Scholar following PRISMA 2020 guidelines. We identified and critically synthesized original studies investigating quercetin-mediated modulation of xenobiotic metabolism, prioritizing mechanistic studies in humans, human pharmacokinetic investigations, and clinically documented drug interactions. RESULTS: Available evidence indicates that quercetin modulates several CYP450 isoforms, phase II enzymes, and major drug transporters, including P-glycoprotein, breast cancer resistance protein, and organic anion transporting polypeptides. Nevertheless, clinically significant pharmacokinetic interactions have been demonstrated for only a limited number of substrates, primarily involving CYP2C9, CYP2E1, and P-glycoprotein, whereas many experimentally predicted interactions have not translated into clinically meaningful effects in humans. Current evidence further highlights the importance of extensive phase II metabolism, circulating conjugated metabolites, transporter-enzyme interplay, and dose-dependent systemic exposure in determining interaction risk. CONCLUSION: Current evidence supports the biological plausibility of quercetin-mediated drug interactions but indicates that their clinical significance is substrate-dependent and remains insufficiently characterized for most therapeutic agents. Well-designed human pharmacokinetic studies using standardized quercetin formulations, validated probe substrates, quantitative pharmacokinetic endpoints, and pharmacogenetic approaches are required to establish evidence-based recommendations for the safe co-administration of quercetin with conventional medications.