Isolation and structural determination of squalene synthase inhibitor from Prunus mume fruit.

Abstract

Squalene synthase plays an important role in the cholesterol biosynthetic pathway. Inhibiting this enzyme in hypercholesterolemia can lower not only plasma cholesterol but also plasma triglyceride levels. A squalene synthase inhibitor was screened from Prunus mume fruit, and then purified via sequential processes of ethanol extraction, HP-20 column chromatography, ethyl acetate extraction, silica gel column chromatography, and crystallization. The squalene synthase inhibitor was identified as chlorogenic acid with a molecular mass of 354 Da and a molecular formula of C16H18O9 based on UV spectrophotometry, 1H and 13C NMRs, and mass spectrometry. Chlorogenic acid inhibited the squalene synthase of pig liver with an IC50 level of 100 nM. Since chlorogenic acid was an effective inhibitor against the squalene synthase of an animal source, it may be a potential therapeutic agent for hypercholesterolemia.

• Authors: Sung-Won Choi, Nam-Yoon Hur, Soon-Cheol Ahn, Dong-Seob Kim, Jae-Kwon Lee, Dae-Ok Kim, Seung-Kook Park, Byung-Yong Kim, Moo-Yeol Baik
• Journal: Journal of microbiology and biotechnology (J Microbiol Biotechnol) Vol. 17 Issue 12 Pg. 1970-5 (Dec 2007) ISSN: 1017-7825 [Print] Korea (South)
• PMID: 18167444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Chlorogenic Acid
• Farnesyl-Diphosphate Farnesyltransferase

Topics

• Chlorogenic Acid (chemistry, isolation & purification, pharmacology)
• Enzyme Inhibitors (chemistry, isolation & purification, pharmacology)
• Farnesyl-Diphosphate Farnesyltransferase (antagonists & inhibitors)
• Fruit (chemistry)
• Inhibitory Concentration 50
• Nuclear Magnetic Resonance, Biomolecular
• Prunus (chemistry)
• Spectrometry, Mass, Electrospray Ionization
• Spectrophotometry, Infrared
• Spectrophotometry, Ultraviolet