title: Atranorin and lecanoric acid antagonize TCDD-induced xenobiotic response element-driven activity, but not xenobiotic response element-independent activity.
abstract: Lichens are symbiotic organisms that consist of fungi and photosynthetic symbionts (algae and/or cyanobacteria). Previous studies of their constituents suggested lichens produce many kinds of aromatic secondary metabolites, such as depsides, quinones, and dibenzofurans. In this study, we evaluated the aryl hydrocarbon receptor (AhR) antagonistic activity of 17 lichen substances and demonstrated that atranorin (1) and lecanoric acid (2), isolated from Parmotrema tinctorum Hale, showed an inhibitory effect on luciferase activity increased by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), using an XRE-driven pX4TK-Luc reporter gene assay. In addition, CYP1A1 mRNA and protein levels increased by TCDD were also suppressed by 1 and 2. Conversely, neither 1 nor 2 antagonized the suppressive effect of TCDD on interleukin (IL)-1β-induced acute-phase response (APR) gene expression. Thus, we concluded that 1 and 2 were selective AhR modulators that antagonize XRE-dependent activity, but not XRE-independent activity. However, 1 has different characteristics to 2 in that 1 alone showed a suppressive effect on IL-1β-induced APR gene expression in a similar fashion to TCDD.
authors.affiliation: Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi, 464-8650, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Nakashima
authors.affiliation: Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi, 464-8650, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanabe
authors.affiliation: Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujii-Kuriyama
authors.affiliation: Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi, 467-8603, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi, 464-8650, Japan. minoue@dpc.aichi-gakuin.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000818:Animals; D056945:Hep G2 Cells; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology*; D008011:Lichens / Q000737:chemistry*; D018336:Receptors, Aryl Hydrocarbon; D012459:Salicylates / Q000494:pharmacology*; D014162:Transfection
chemical_list: D062385:Hydroxybenzoates; D018336:Receptors, Aryl Hydrocarbon; D012459:Salicylates; C026304:atranorin; C008263:lecanoric acid
keywords: Aryl hydrocarbon receptor; Atranorin; Lecanoric acid; Lichen substances; Selective AhR modulators