Antcins, triterpenoids from Antrodia cinnamomea, as new agonists for peroxisome proliferator-activated receptor α.
Antrodia cinnamomea
Drug discovery
Metabolism
Nuclear receptor
Peroxisome proliferator-activated receptor α
Journal
Journal of food and drug analysis
ISSN: 2224-6614
Titre abrégé: J Food Drug Anal
Pays: China (Republic : 1949- )
ID NLM: 101630927
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
28
09
2018
revised:
08
11
2018
accepted:
21
11
2018
entrez:
17
1
2019
pubmed:
17
1
2019
medline:
24
3
2020
Statut:
ppublish
Résumé
Peroxisome proliferator-activated receptor α (PPARα) is a nuclear hormone receptor that transcriptionally regulates lipid metabolism and inflammation; therefore, PPARα agonists are promising agents to treat dyslipidemia and metabolic disorders. PPARα full agonists, such as fibrates, are effective anti-hypertriglyceride agents, but their use is limited by adverse side effects. Hence, the aim of this study was to identify small molecules that can activate PPARα while minimizing the adverse effects. Antrodia cinnamomea, a rare medical mushroom, has been used widely in Asian countries for the treatment of various diseases, including liver diseases. Antcin B, H and K (antcins) and ergostatrien-3β-ol (EK100) are bioactive compounds isolated from A. cinnamomea with anti-inflammatory actions. Antcins, ergostane-type triterpenoids, contain the polar head with carboxylate group and the sterol-based body. Here, we showed at the first time that sterol-based compounds, antcins, but not EK100, activate PPARα in a cell-based transactivation study. The in silico docking studies presented several significant molecular interactions of antcins, including Tyr314, and His440 in the ligand-binding domain of PPARα, and these interactions are required for helix 12 (H12) stabilization. We propose that PPARα activation activity of antcins is related to their binding mode which requires conventional H12 stabilization, and that antcins can be developed as safe selective PPARα modulators.
Identifiants
pubmed: 30648583
pii: j.jfda.2018.11.004
doi: 10.1016/j.jfda.2018.11.004
pmc: PMC9298643
doi:
Substances chimiques
Cholestenes
0
Cholestenones
0
PPAR alpha
0
Plant Extracts
0
Triterpenes
0
antcin B
0
antcin H
0
antcin K
0
Ergosterol
Z30RAY509F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
295-304Informations de copyright
Copyright © 2018. Published by Elsevier Taiwan LLC.
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