Gerontoxanthone B from Maclura cochinchinensis var. gerontogea exhibits anti-inflammatory potential as an aryl hydrocarbon receptor agonist

• Published in: Bioorganic & medicinal chemistry Vol. 25; no. 16; pp. 4253 - 4258
• Main Authors: Nakashima, Ken-ichi, Ogiwara, Takumi, Hirai, Takao, Tanaka, Toshiyuki, Murata, Hiroko, Kaburagi, Kouichi, Fujii-Kuriyama, Yoshiaki, Hayashi, Hidetoshi, Inoue, Makoto
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.08.2017
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Aryl hydrocarbon receptor (AhR); Cytochrome P450 1A1 (CYP1A1); Dose-Response Relationship, Drug; Hep G2 Cells; Humans; Maclura - chemistry; Maclura cochinchinensis var. gerontogea; Molecular Structure; Moraceae; Receptors, Aryl Hydrocarbon - agonists; Structure-Activity Relationship; Tumor Cells, Cultured; Xanthones; Xanthones - chemistry; Xanthones - isolation & purification; Xanthones - pharmacology; Cytochrome P450 1A1 (CYP1A1); Aryl hydrocarbon receptor (AhR); Xanthones; Moraceae; Maclura cochinchinensis var. gerontogea
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2017.05.047

[Display omitted] The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcriptional factor belonging to the basic helix-loop-helix-Per-Ahr/Arnt-Sim family. In this study, we evaluated the AhR agonistic activities of 12 xanthones isolated from the roots of M. cochinchinensis var. gerontogea using HepG2 cells transfected with pX4TK–Luc reporter plasmids. Gerontoxanthone B (GXB) showed the most potent activity at a concentration of 10μM, and the activity was inhibited by AhR antagonists such as GNF-351. GXB also increased cytochrome P450 1A1 mRNA and protein levels in HepG2 cells. Similar to the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin, however, GXB suppressed the IL-1β-induced mRNA level of SAA1, an acute-phase response gene that is up-regulated AhR-dependently but XRE-independently. Thus, GXB shows XRE-dependent transcriptional activity and XRE-independent activity involving AhR.