Herbs are often administered in combination with therapeutic drugs, raising the possibility for herb–drug interactions (HDIs). Furoquinoline alkaloids are found in Rutaceae plants, which are structurally similar and have many medicinal properties. This study aims to investigate the inhibition of four furoquinoline alkaloids on the activity of UDP-glucuronosyltransferases (UGTs).

The recombinant UGTs-catalyzed glucuronidation metabolism of 4-methylumbelliferone (4-MU) was utilized to investigate the inhibition potential. Inhibition type and parameters were determined, and in silico docking was employed to elucidate the inhibition difference of furoquinoline alkaloids towards UGTs.

Dictamine, haplopine, γ-fagarine and skimmianine strongly inhibited UGT1A3, UGT1A7, UGT1A9 and UGT2B4, respectively. Among them, dictamnine inhibited more than 70% of the four UGTs. Inhibition kinetics determination showed that they all exerted competitive inhibition, and the inhibition kinetic constant (K_i) was determined to be 8.3, 7.2, 3.7 and 33.9 μM, respectively. In vitro–in vivo extrapolation (IVIVE) was employed to demonstrate the inhibition possibility for four alkaloids. Skimmianine was proved to be more suitable for clinical application. In silico docking study indicated that the hydrophobic interactions played a key role in the inhibition of furoquinoline alkaloids towards three of the four UGTs. In conclusion, monitoring the interactions between furoquinoline alkaloids and drugs mainly undergoing UGTs-catalyzed metabolism is necessary.

草药通常与治疗药物联合使用，从而增加了草药与药物相互作用（HDI）的可能性。在芸苔科植物中发现了呋喃喹啉生物碱，它们在结构上相似并且具有许多药用特性。这项研究旨在调查四种呋喃喹啉生物碱对UDP-葡萄糖醛酸糖基转移酶（UGTs）活性的抑制作用。

利用重组UGTs催化的4-甲基伞形酮（4-MU）的葡萄糖醛酸代谢来研究其抑制潜力。确定了抑制类型和参数，并通过计算机对接来阐明呋喃喹啉生物碱对UGT的抑制差异。

Dictamine，haplopine，γ-fagarine和skimmianine分别强烈抑制UGT1A3，UGT1A7，UGT1A9和UGT2B4。其中，烟酰胺抑制了四种UGT中的70％以上。抑制动力学测定表明它们都发挥竞争抑制作用，并且抑制动力学常数（K _i）分别确定为8.3、7.2、3.7和33.9μM。体外-体内外推法（IVIVE）用于证明对四种生物碱具有抑制作用。Skimmianine被证明更适合临床应用。电脑对接研究表明，疏水相互作用在抑制呋喃喹啉生物碱对四种UGT中的三种中起关键作用。总之，有必要监测呋喃喹啉生物碱与主要经历UGTs催化代谢的药物之间的相互作用。