Paris saponins, also known as polyphyllins, are natural compounds extracted from Paris polyphylla, which have many pharmacological activities, such as anti-inflammation and anti-cancer. In particular, paris saponin I, II, VII and polyphyllin VI are the components of the quality standard for Paris polyphylla. However, the inhibition risk of polyphyllins on cytochrome P450 (CYP) and UDP-glucuronosyltransferases (UGT) remains unclear. Therefore, this report investigated the potential inhibitory effects of paris saponin I, II, VII and polyphyllin VI on the activities of CYP (CYP1A2, CYP2B1, CYP2C11, CYP2D1, CYP2E1 and CYP3A2) and UGT (UGT1A1, UGT1A3, UGT1A6, PROG and AZTG) through cocktail inhibition assays in vitro. In the study of CYP, polyphyllin VI exhibited weak inhibition on CYP2D1 activity in rat liver microsomes with IC50 value at 45.2 μM, while paris saponin VII weakly inhibited CYP2C11 and CYP2E1 activities with IC50 value at 42.0 and 67.7 μM, respectively. In the study of UGT, none of the four steroidal saponins showed significant inhibition risk. In conclusion, paris saponin I, II, VII and polyphyllin VI have very low potential to cause the possible toxicity and drug interactions involving CYP and UGT enzymes, indicating that they are safe enough to take with drugs.

中文翻译：

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通过鸡尾酒抑制试验评估巴黎皂苷，巴黎多叶植物的生物活性化合物对CYP和UGT酶的抑制风险。

巴黎皂苷，也称为多叶素，是从多叶巴黎提取的天然化合物，具有许多药理活性，例如抗炎和抗癌。尤其是巴黎皂苷I，II，VII和多叶素VI是巴黎多叶植物质量标准的组成部分。但是，尚不清楚多叶素对细胞色素P450（CYP）和UDP-葡萄糖醛酸糖基转移酶（UGT）的抑制风险。因此，本报告调查了巴黎皂苷I，II，VII和多叶素VI对CYP（CYP1A2，CYP2B1，CYP2C11，CYP2D1，CYP2E1和CYP3A2）和UGT（UGT1A1，UGT1A3，UGG1A6和TGP1A6的活性的潜在抑制作用）进行体外鸡尾酒抑制试验。在CYP的研究中，polyphyllin VI对大鼠肝微粒体的CYP2D1活性表现出微弱的抑制作用，IC50值为45.2μM，巴黎皂苷VII弱抑制CYP2C11和CYP2E1活性，IC50值分别为42.0和67.7μM。在UGT的研究中，四种甾体皂苷均未显示出明显的抑制风险。总之，巴黎皂苷I，II，VII和多叶绿素VI潜在低下，可能引起涉及CYP和UGT酶的毒性和药物相互作用，这表明它们与药物合用时足够安全。