title: Pregnane X receptor-mediated transcriptional activation of UDP-glucuronosyltransferase 1A1 by natural constituents from foods and herbs.
abstract: The induction of drug-metabolising enzymes is being increasingly recognised for its clinical importance in drug research and development. In the present study, we used a pregnane X receptor (PXR)-mediated reporter gene assay to evaluate the activating effects of various food, herb, and horticultural plant constituents on the PXR and a UGT1A1 reporter gene DNA construct. The results showed that of 102 naturally occurring constituents tested, 50 activated the PXR signaling pathway and induced expression of the UGT1A1-reporter gene DNA construct. Eleven constituents strongly induced gene expression (a response of >70% compared to that associated with rifampicin), and were further evaluated in in vitro experiments to confirm the induction of UGT1A1 mRNA and protein expression. The results suggest that foods and herbs containing these constituents should be consumed with caution to avoid undesirable drug-drug interactions with co-administered drugs that are substrates for UGT1A1.
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China; The Children's Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Huang
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Hu
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address: yuls@zju.edu.cn.
authors.forename: Lushan
authors.initials: L
authors.lastname: Yu
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
mesh_terms: D017930:Genes, Reporter; D014453:Glucuronosyltransferase / Q000235:genetics*; D056945:Hep G2 Cells; D006801:Humans; D064209:Phytochemicals / Q000494:pharmacology*; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000235:genetics; D011987:Receptors, Steroid / Q000187:drug effects* / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects*; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D064209:Phytochemicals; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D011987:Receptors, Steroid; D000099148:UGT1A1 Enzyme
keywords: Induction; Natural constituents; PXR; UGT1A1