UDP-glucuronosyltransferase 1A9 (UGT1A9) is one of the most important UGT isoforms, and plays an important role in the metabolic elimination of therapeutic drugs via glucuronidation. Herbal medicines affecting the activity of UGT1A9 may influence the metabolism of related drugs, thus causing herb-drug interactions and even adverse effects. However, few methods are available to evaluate the activity of UGT1A9. In this study, a natural product glabrone was discovered as an isoform-specific probe substrate for UGT1A9. The V_max and K_m values of glabrone were 362.6 nmol/min/mg protein and 17.2 μM for human liver microsomes (HLMs), and 382.3 nmol/min/mg protein and 16.6 μM for recombinant human UGT1A9, respectively. Glabrone 7-O-glucuronide, the UGT1A9 metabolite of glabrone, was prepared by using a plant glucuronosyltransferase UGT88D1, and the structure was identified by NMR spectroscopy. Using glabrone as a probe, we established a rapid HPLC method to screen UGT1A9 inhibitors from 54 natural products isolated from the Chinese herbal medicine licorice. Among them, glycycoumarin was found as a potent UGT1A9 inhibitor with an IC₅₀ value of 6.04 μM. In rats, the pretreatment of glycycoumarin (4 mg/kg, i.p.) for 3 days could remarkably increase the plasma concentrations of dapagliflozin while decrease the concentrations of dapagliflozin-O-glucuronide after administration of dapagliflozin (1 mg/kg, i.v.), which is mainly metabolized by UGT1A9. The results indicated the potential risk of herb-drug interactions between licorice and UGT1A9-metabolizing drugs.

UDP-葡糖醛酸糖基转移酶1A9（UGT1A9）是最重要的UGT亚型之一，在通过葡糖醛酸化作用的治疗药物的代谢消除中起重要作用。影响UGT1A9活性的草药可能会影响相关药物的代谢，从而引起草药与药物的相互作用，甚至产生不良影响。但是，很少有方法可以评估UGT1A9的活性。在这项研究中，发现了天然产物葛根酮作为UGT1A9的同工型特异性探针底物。对于人肝微粒体（HLM），葛兰素的V _max和K _m值分别为362.6 nmol / min / mg蛋白和17.2μM，而对于重组人UGT1A9，它们的V _max和K _m值分别为382.3 nmol / min / mg蛋白和16.6μM。Glabrone 7- Oβ-葡糖醛酸苷，一种葛兰素的UGT1A9代谢物，是使用植物葡糖醛酸糖基转移酶UGT88D1制备的，其结构通过NMR光谱法鉴定。我们使用甘草酮作为探针，建立了一种快速HPLC方法，以从中草药甘草中分离出的54种天然产物中筛选UGT1A9抑制剂。其中，发现香豆素是有效的UGT1A9抑制剂，IC ₅₀值为6.04μM 。在大鼠中，对大豆香豆素（4 mg / kg，腹膜内）进行3天的预处理可显着增加dapagliflozin的血浆浓度，同时降低dapagliflozin- O的浓度达格列净（1 mg / kg，静脉内）给药后的β-葡萄糖醛酸，其主要由UGT1A9代谢。结果表明，甘草与UGT1A9代谢药物之间存在药草相互作用的潜在风险。