Department of Biological Sciences, Graduate School of Sookmyung Women's University, Seoul 04310, Korea.
Department of Biology Education, College of Education, Sookmyung Women's University, Seoul 04310, Korea.
Int J Mol Sci. 2018 Oct 30;19(11):3400. doi: 10.3390/ijms19113400.
(OFI) is grown abundantly in arid areas and its fruits are regarded as an important food and nutrient source owing to the presence of flavonoids, minerals, and proteins. The previous report that OFI exerts phytoestrogenic activity makes it plausible for OFI-containing supplements to be used as alternative estrogen replacement therapy. In the case of polypharmacy with the consumption of OFI-containing botanicals in post- or peri-menopausal women, it is critical to determine the potential drug-OFI interaction due to the modulation of drug metabolism. In the present study, the modulating effects on the hepatic drug metabolizing enzymes (DMEs) by OFI and its flavonoid constituents (kaempferol, quercetin, isorhamnetin, and their glycosidic forms) were investigated using the liver microsomal fractions prepared from ovariectomized (OVX) rats, human liver microsomes, and human hepatocarcinoma cell line (HepG2). As a result, the oral administration of extracts of OFI (OFIE) in OVX rats induced hepatic CYP2B1, CYP3A1, and UGT2B1. OFIE, hydrolyzed (hdl) OFIE, and several flavonols induced the transcriptional activities of both CYP2B6 and CYP3A4 genes in HepG2 cells. Finally, OFIE did not inhibit activities of cytochrome P450 (CYPs) or uridine diphosphate (UDP)-glucuronosyltransferases (UGTs), whereas hdl OFIE or flavonol treatment inhibited CYP1A2 and CYP3A1/3A4 in rat and human liver microsomes. Our data demonstrate that OFIE may induce or inhibit certain types of DMEs and indicate that drug-OFI interaction may occur when the substrate or inhibitor drugs of specific CYPs or UGTs are taken concomitantly with OFI-containing products.
（OFI）在干旱地区大量生长，其果实因其含有类黄酮、矿物质和蛋白质而被视为重要的食物和营养来源。之前有报道称 OFI 具有植物雌激素活性，因此含有 OFI 的补充剂可能被用作替代雌激素替代疗法。对于绝经后或围绝经期妇女同时服用含有 OFI 的植物药的多药治疗，由于药物代谢的调节，确定潜在的药物-OFI 相互作用至关重要。在本研究中，使用从卵巢切除（OVX）大鼠、人肝微粒体和人肝癌细胞系（HepG2）制备的肝微粒体部分研究了 OFI 及其类黄酮成分（山奈酚、槲皮素、异鼠李素及其糖苷形式）对肝药物代谢酶（DMEs）的调节作用。结果，OFI（OFIE）提取物口服给予 OVX 大鼠可诱导肝 CYP2B1、CYP3A1 和 UGT2B1。OFIE、水解（hdl）OFIE 和几种类黄酮在 HepG2 细胞中诱导 CYP2B6 和 CYP3A4 基因的转录活性。最后，OFIE 不会抑制细胞色素 P450（CYPs）或尿苷二磷酸（UDP）-葡萄糖醛酸基转移酶（UGTs）的活性，而 hdl OFIE 或类黄酮处理抑制了大鼠和人肝微粒体中的 CYP1A2 和 CYP3A1/3A4。我们的数据表明，OFIE 可能诱导或抑制某些类型的 DMEs，并表明当特定 CYP 或 UGT 的底物或抑制剂药物与含有 OFI 的产品同时服用时，可能会发生药物-OFI 相互作用。
