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Bioorg Med Chem. 2017 Aug 15;25(16):4253-4258. doi: 10.1016/j.bmc.2017.05.047. Epub 2017 Jun 15.

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

Author information

1
Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University, 1-100, Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan.
2
Laboratory of Natural Resources, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
3
Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
4
Nakatane-cho, Kumage-gun, Kagoshima, Japan.
5
Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
6
Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori, Mizuho-ku, Nagoya 467-8603, Japan.
7
Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University, 1-100, Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan. Electronic address: minoue@dpc.aichi-gakuin.ac.jp.

Abstract

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.

KEYWORDS:

Aryl hydrocarbon receptor (AhR); Cytochrome P450 1A1 (CYP1A1); Maclura cochinchinensis var. gerontogea; Moraceae; Xanthones

PMID:
28662965
DOI:
10.1016/j.bmc.2017.05.047
[Indexed for MEDLINE]

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