College of Pharmacy and Intergrated Research Institute for Drug Development, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang, Gyonggi-do 10326, Korea.
Molecules. 2018 Feb 9;23(2):366. doi: 10.3390/molecules23020366.
Herb-drug interaction (HDI) limits clinical application of herbs and drugs, and inhibition of herbs towards uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) has gained attention as one of the important reasons to cause HDIs. Sauchinone, an active lignan isolated from aerial parts of (Saururacease), possesses anti-oxidant, anti-inflammatory, and anti-viral activities. In pharmacokinetics of sauchinone, sauchinone is highly distributed to the liver, forming extensive metabolites of sauchinone via UGTs in the liver. Thus, we investigated whether sauchinone inhibited UGTs to explore potential of sauchinone-drug interactions. In human liver microsomes (HLMs), sauchinone inhibited activities of UGT1A1, 1A3, 1A6, and 2B7 with IC values of 8.83, 43.9, 0.758, and 0.279 μM, respectively. Sauchinone also noncompetitively inhibited UGT1A6 and 2B7 with values of 1.08 and 0.524 μM, respectively. In in vivo interaction study using mice, sauchinone inhibited UGT2B7-mediated zidovudine metabolism, resulting in increased systemic exposure of zidovudine when sauchinone and zidovudine were co-administered together. Our results indicated that there is potential HDI between sauchinone and drugs undergoing UGT2B7-mediated metabolism, possibly contributing to the safe use of sauchinone and drug combinations.
草药-药物相互作用（HDI）限制了草药和药物的临床应用，而草药对尿苷二磷酸（UDP）-葡萄糖醛酸基转移酶（UGTs）的抑制作用已成为引起 HDI 的重要原因之一。莪术呋喃二酮是从莪术（Saururacease）地上部分分离得到的一种活性木脂素，具有抗氧化、抗炎和抗病毒活性。在莪术呋喃二酮的药代动力学中，莪术呋喃二酮高度分布到肝脏，在肝脏中通过 UGTs 形成莪术呋喃二酮的广泛代谢物。因此，我们研究了莪术呋喃二酮是否抑制 UGTs，以探讨其潜在的药物相互作用。在人肝微粒体（HLMs）中，莪术呋喃二酮对 UGT1A1、1A3、1A6 和 2B7 的活性具有抑制作用，IC 值分别为 8.83、43.9、0.758 和 0.279 μM。莪术呋喃二酮还对 UGT1A6 和 2B7 具有非竞争性抑制作用，Ki 值分别为 1.08 和 0.524 μM。在使用小鼠的体内相互作用研究中，莪术呋喃二酮抑制了 UGT2B7 介导的齐多夫定代谢，当莪术呋喃二酮和齐多夫定同时给药时，导致齐多夫定的全身暴露增加。我们的结果表明，莪术呋喃二酮与经 UGT2B7 介导代谢的药物之间存在潜在的 HDI，这可能有助于莪术呋喃二酮和药物组合的安全使用。
