Abstract
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 Saururus chinensis (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 IC50 values of 8.83, 43.9, 0.758, and 0.279 μM, respectively. Sauchinone also noncompetitively inhibited UGT1A6 and 2B7 with Ki 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.
Highlights
Herb–drug combinations have been steadily increased and encouraged as main medical treatments by the World Health Organization [1,2]
Inhibition of drug-metabolic enzymes in drug combination therapies is considered an important origin of adverse effects
Along with the upsurge of herb–drug combinations, inhibition of herbs towards drug-metabolic enzymes in Herb–drug interaction (HDI) has been raised as an important reason that limits clinical applications of herbs and drugs [17,27]
Summary
Herb–drug combinations have been steadily increased and encouraged as main medical treatments by the World Health Organization [1,2]. Since herb–drug interactions (HDIs) can limit clinical application of herbs and drugs, inhibition of herbs toward uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) has received attention in association with alternations of drug efficacy or toxicity [3,4,5]. UGTs are phase II metabolic enzymes that predominantly catalyze glucuronidation of xenobiotics, including approximately 35% of drugs and facilitating elimination of glucuronidated metabolites through bile and urine [6,7]. Glucuronidation clears drugs because glucuronidated metabolites have more polarity and water solubility. It detoxifies drugs because glucuronidated metabolites possess less activity or toxicity than their parent forms [8]. Many cases of UGT inhibition-mediated drug interactions have been reported [5,7] including UGT1A1 inhibition by psoralidin that causes irinotecan’ toxicity [9], UGT1A3 inhibition by gemfibrozil that enhances susceptibility of statins [10], UGT1A6 inhibition by silybin that attenuates fenofibrate-induced
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
