title: Artemisinin protects against dextran sulfate-sodium-induced inflammatory bowel disease, which is associated with activation of the pregnane X receptor.
abstract: Artemisinin has been used to treat malaria for centuries in the context of traditional Chinese medicine. In the present study, the effects of artemisinin on pregnane X receptor (PXR)-mediated CYP3A expression and its therapeutic role in inflammatory bowel disease were investigated. LS174T cells exposed to artemisinin at various concentrations and for different periods of time were examined with respect to the specific induction of CYP3A4 and PXR mRNA expression. Transient transfection experiments showed transcriptional activation of the CYP3A4 gene through artemisinin to be PXR-dependent. An electrophoretic-mobility shift assay (EMSA) showed that artemisinin activates the DNA-binding capacity of the PXR for the CYP3A4 element. These results indicate that the induction of CYP3A4 by artemisinin is mediated through the activation of PXR. Using animal models, it was demonstrated that artemisinin abrogates dextran sulfate sodium (DDS)-induced intestinal inflammation. Preadministration of artemisinin ameliorated the clinical hallmarks of colitis in DSS-treated mice as determined by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. Artemisinin was found to prevent or reduce the severity of colonic inflammation by inducing CYP3A expression by activation of PXR.
authors.affiliation: Department of Pharmacology, Anhui Medical University, Hefei 230032, China.
authors.forename: Donghua
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Taiping Road 27, Haidian, Beijing 100850, China.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Anhui Medical University, Hefei 230032, China.
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Taiping Road 27, Haidian, Beijing 100850, China.
authors.forename: Zengchun
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Taiping Road 27, Haidian, Beijing 100850, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: You
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Taiping Road 27, Haidian, Beijing 100850, China.
authors.forename: Xianxie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Taiping Road 27, Haidian, Beijing 100850, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Taiping Road 27, Haidian, Beijing 100850, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Taiping Road 27, Haidian, Beijing 100850, China.
authors.forename: Qiande
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Taiping Road 27, Haidian, Beijing 100850, China.
authors.forename: Hongling
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Taiping Road 27, Haidian, Beijing 100850, China.
authors.forename: Chengrong
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Taiping Road 27, Haidian, Beijing 100850, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Tang
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Boli
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Taiping Road 27, Haidian, Beijing 100850, China. Electronic address: gaoyue@nic.bmi.ac.cn.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D016264:Dextran Sulfate / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008024:Ligands; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D037621:Artemisinins; D008024:Ligands; D016328:NF-kappa B; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D011987:Receptors, Steroid; D016264:Dextran Sulfate; C031327:artemisinin; D051544:Cytochrome P-450 CYP3A
keywords: Artemisinin; Cytochrome 3A; Dextran sodium sulfate; Inflammatory bowel disease; Pregnane X receptor