Isolation and structural determination of squalene synthase inhibitor from Prunus mume fruit.
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.
Choi
Sung-Won
SW
Department of Food and Culinary Art, Osan College, Osan 447-749, Korea.
Hur
Nam-Yoon
NY
Ahn
Soon-Cheol
SC
Kim
Dong-Seob
DS
Lee
Jae-Kwon
JK
Kim
Dae-Ok
DO
Park
Seung-Kook
SK
Kim
Byung-Yong
BY
Baik
Moo-Yeol
MY
D002726:Chlorogenic Acid / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D005638:Fruit / Q000737:chemistry; D020128:Inhibitory Concentration 50; D019906:Nuclear Magnetic Resonance, Biomolecular; D027861:Prunus / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D004791:Enzyme Inhibitors; D002726:Chlorogenic Acid; D013186:Farnesyl-Diphosphate Farnesyltransferase