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黄酮类化合物作为CYP3A4体外抑制剂

Flavonoids as CYP3A4 Inhibitors In Vitro.

作者信息

Kondža Martin, Brizić Ivica, Jokić Stela

机构信息

Faculty of Pharmacy, University of Mostar, Matice hrvatske bb, 88000 Mostar, Bosnia and Herzegovina.

University Clinical Hospital Mostar, Kralja Tvrtka bb, 88000 Mostar, Bosnia and Herzegovina.

出版信息

Biomedicines. 2024 Mar 13;12(3):644. doi: 10.3390/biomedicines12030644.

Abstract

Flavonoids, a diverse group of polyphenolic compounds found abundantly in fruits, vegetables, and beverages like tea and wine, offer a plethora of health benefits. However, they have a potential interaction with drug metabolism, particularly through the inhibition of the cytochrome P450 3A4 enzyme, the most versatile and abundant enzyme in the liver. CYP3A4 is responsible for metabolizing approximately 50% of clinically prescribed drugs across diverse therapeutic classes, so these interactions have raised concerns about potential adverse effects. This review delves into the scientific evidence surrounding flavonoid-mediated CYP3A4 inhibition, exploring the inhibitory potential of investigated flavonoids and future implications. Kusehnol I, chrysin, leachianone A, and sophoraflavone G showed the largest inhibitory potentials and lowest values. While the clinical significance of flavonoid-mediated CYP3A4 inhibition in dietary contexts is generally considered low due to moderate intake and complex interactions, it poses a potential concern for individuals consuming high doses of flavonoid supplements or concurrently taking medications metabolized by CYP3A4. This can lead to increased drug exposure, potentially triggering adverse reactions or reduced efficacy.

摘要

黄酮类化合物是一类多样的多酚化合物,大量存在于水果、蔬菜以及茶和葡萄酒等饮品中,具有诸多健康益处。然而,它们与药物代谢存在潜在相互作用,尤其是通过抑制细胞色素P450 3A4酶,该酶是肝脏中最具通用性且含量丰富的酶。CYP3A4负责代谢约50%的各类临床处方药,因此这些相互作用引发了对潜在不良反应的担忧。本综述深入探讨了围绕黄酮类化合物介导的CYP3A4抑制作用的科学证据,探究了所研究黄酮类化合物的抑制潜力及未来影响。库瑟诺醇I、白杨素、刺桐酮A和槐黄酮G表现出最大的抑制潜力和最低值。虽然由于摄入量适中且相互作用复杂,黄酮类化合物介导的CYP3A4抑制作用在饮食环境中的临床意义通常被认为较低,但对于服用高剂量黄酮类补充剂或同时服用由CYP3A4代谢的药物的个体而言,这是一个潜在问题。这可能导致药物暴露增加, potentially triggering adverse reactions or reduced efficacy.(原文此处有误,根据前文推测应改为“可能引发不良反应或疗效降低”)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7605/10968035/18aac801dd54/biomedicines-12-00644-g001.jpg

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