尿苷二磷酸葡萄糖醛酸轉(zhuǎn)移酶1A1（UGT1A1）是哺乳動(dòng)物體內(nèi)分布的一種重要的Ⅱ相代謝酶，其不僅介導(dǎo)了大量臨床藥物、毒物的代謝清除，還是機(jī)體參與內(nèi)源性毒性物質(zhì)膽紅素代謝清除的唯一代謝酶。藥物或食品中的化學(xué)成分對(duì)UGT1A1的強(qiáng)烈抑制會(huì)引發(fā)多種不良反應(yīng)，如藥物/草藥-藥物相互作用、高膽紅素血癥、肝功能異常及神經(jīng)毒性等。近年來，研究發(fā)現(xiàn)許多草藥提取物及其化學(xué)成分可通過強(qiáng)效抑制UGT1A1引發(fā)藥物-草藥相互作用等不良反應(yīng)。結(jié)合藥物代謝及藥物毒理學(xué)相關(guān)領(lǐng)域的新近研究進(jìn)展，系統(tǒng)總結(jié)了UGT1A1抑制劑篩選與評(píng)價(jià)常用方法，以及中草藥化學(xué)成分對(duì)UGT1A1抑制作用的研究進(jìn)展。上述信息對(duì)于臨床安全合理的使用中草藥，尤其是在中西藥聯(lián)用或中藥方劑使用過程中盡可能避免因UGT1A1抑制引發(fā)的不良反應(yīng)，具有重要指導(dǎo)意義。

UDP-glucuronosyltransferase 1A1 (UGT1A1) is a key conjugative enzyme distributed in mammalian tissues. UGT1A1 is crucial for the detoxification of many clinical drugs and toxins, and is also the sole physiologically relevant enzyme participating in the metabolic elimination of bilirubin, an endogenous toxic metabolite. Strong inhibition on the catalytic activity of UGT1A1 by therapeutic drugs or chemical constitutes in herb or foods could trigger clinical adverse reactions, such as drug/herb-drug interactions, hyperbilirubinemia, hepatotoxicity and neurotoxicity. Recently, herb extracts and their chemical ingredients have been reported to exhibit strong inhibitory effects on UGT1A1 and may cause several adverse reactions. This review systemically summarizes the currently used methods for the screening and characterization of UGT1A1 inhibitors, and the inhibitory effects of herb extracts and their constitutes on UGT1A1, on the basis of the recent advances in the fields of drug metabolism and drug toxicology. All information and knowledge presented in this review will be very helpful for the reasonable and safety usage of Chinese Herbal Medicines in clinic, especially for avoiding the occurrence of adverse reactions via UGT1A1 inhibition when herb medicines were used combined with clinical drugs.

國家自然科學(xué)基金（81773687，81703606，81573501,81473181）；國家重點(diǎn)研發(fā)計(jì)劃（2017YFC1700200，2017YFC1702000）；國家科技重大專項(xiàng)（2017ZX09101004）；新疆生產(chǎn)建設(shè)兵團(tuán)科技攻關(guān)與成果轉(zhuǎn)化項(xiàng)目（2016AD008）