Document Detail


Effect of 26-oxygenosterols from Ganoderma lucidum and their activity as cholesterol synthesis inhibitors.
MedLine Citation:
PMID:  16000773     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ganoderma lucidum is a medicinal fungus belonging to the Polyporaceae family which has long been known in Japan as Reishi and has been used extensively in traditional Chinese medicine. We report the isolation and identification of the 26-oxygenosterols ganoderol A, ganoderol B, ganoderal A, and ganoderic acid Y and their biological effects on cholesterol synthesis in a human hepatic cell line in vitro. We also investigated the site of inhibition in the cholesterol synthesis pathway. We found that these oxygenated sterols from G. lucidum inhibited cholesterol biosynthesis via conversion of acetate or mevalonate as a precursor of cholesterol. By incorporation of 24,25-dihydro-[24,25-3H2]lanosterol and [3-3H]lathosterol in the presence of ganoderol A, we determined that the point of inhibition of cholesterol synthesis is between lanosterol and lathosterol. These results demonstrate that the lanosterol 14alpha-demethylase, which converts 24,25-dihydrolanosterol to cholesterol, can be inhibited by the 26-oxygenosterols from G. lucidum. These 26-oxygenosterols could lead to novel therapeutic agents that lower blood cholesterol.
Authors:
Hassan Hajjaj; Catherine Mac?; Matthew Roberts; Peter Niederberger; Laurent B Fay
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Applied and environmental microbiology     Volume:  71     ISSN:  0099-2240     ISO Abbreviation:  Appl. Environ. Microbiol.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-07     Completed Date:  2005-09-13     Revised Date:  2010-04-06    
Medline Journal Info:
Nlm Unique ID:  7605801     Medline TA:  Appl Environ Microbiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3653-8     Citation Subset:  IM    
Affiliation:
Nestl? Research Centre, Nestec Ltd., Vers-chez-les-Blanc, P.O. Box 44, 1000 Lausanne 26, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Anticholesteremic Agents / pharmacology*
Cell Line
Cholesterol / biosynthesis*
Cytochrome P-450 Enzyme System / antagonists & inhibitors
Gas Chromatography-Mass Spectrometry
Humans
Lanosterol / analogs & derivatives*,  biosynthesis,  pharmacology*
Liver / cytology,  drug effects
Magnetic Resonance Spectroscopy
Oxidoreductases / antagonists & inhibitors
Reishi / growth & development,  metabolism*
Chemical
Reg. No./Substance:
0/Anticholesteremic Agents; 57-88-5/Cholesterol; 79-63-0/Lanosterol; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Oxidoreductases; EC 1.14.13.70/sterol 14-demethylase
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