2014年12月
Fomiroid A, a Novel Compound from the Mushroom Fomitopsis nigra, Inhibits NPC1L1-Mediated Cholesterol Uptake via a Mode of Action Distinct from That of Ezetimibe
PLOS ONE
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- 巻
- 9
- 号
- 12
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1371/journal.pone.0116162
- 出版者・発行元
- PUBLIC LIBRARY SCIENCE
Hypercholesterolemia is one of the key risk factors for coronary heart disease, a major cause of death in developed countries. Suppression of NPC1L1-mediated dietary and biliary cholesterol absorption is predicted to be one of the most effective ways to reduce the risk of hypercholesterolemia. In a screen for natural products that inhibit ezetimibe glucuronide binding to NPC1L1, we found a novel compound, fomiroid A, in extracts of the mushroom Fomitopsis nigra. Fomiroid A is a Ianosterone derivative with molecular formula C30H48O3. Fomiroid A inhibited ezetimibe glucuronide binding to NPC1L1, and dose-dependently prevented NPC1L1-mediated cholesterol uptake and formation of esterified cholesterol in NPC1L1-expressing Caco2 cells. Fomiroid A exhibited a pharmacological chaperone activity that corrected trafficking defects of the L1072T/L1168I mutant of NPC1L1. Because ezetimibe does not have such an activity, the binding site and mode of action of fomiroid A are likely to be distinct from those of ezetimibe.
- リンク情報
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- DOI
- https://doi.org/10.1371/journal.pone.0116162
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/25551765
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000347119100104&DestApp=WOS_CPL
- URL
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85017330805&origin=inward
- ID情報
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- DOI : 10.1371/journal.pone.0116162
- ISSN : 1932-6203
- PubMed ID : 25551765
- SCOPUS ID : 85017330805
- Web of Science ID : WOS:000347119100104