title: Evodiamine as a novel antagonist of aryl hydrocarbon receptor.
abstract: Evodiamine, the major bioactive alkaloid isolated from Wu-Chu-Yu, has been shown to interact with a wide variety of proteins and modify their expression and activities. In this study, we investigated the interaction between evodiamine and the aryl hydrocarbon receptor (AhR). Molecular modeling results revealed that evodiamine directly interacted with the AhR. Cytosolic receptor binding assay also provided the evidence that evodiamine could interact with the AhR with the K(i) value of 28.4±4.9nM. In addition, we observed that evodiamine suppressed the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced nuclear translocation of the AhR and the expression of CYP1A1 dose-dependently. These results suggested that evodiamine was able to bind to the AhR as ligand and exhibit antagonistic effects.
authors.affiliation: State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.forename: Yongjiu
authors.initials: Y
authors.lastname: Tu
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Fan
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Zhanli
authors.initials: Z
authors.lastname: Wang
authors.forename: Huaping
authors.initials: H
authors.lastname: Liang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000737:chemistry; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D011487:Protein Conformation; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000737:chemistry
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019363:Cytochrome P-450 CYP1A1; D010936:Plant Extracts; D011799:Quinazolines; D018336:Receptors, Aryl Hydrocarbon; C111235:AHR protein, human; C049639:evodiamine