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

[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 u...

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Bibliographic Details
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
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Summary:	[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.
ISSN:	0968-0896 1464-3391
DOI:	10.1016/j.bmc.2017.05.047