Bavachin and isobavachalcone, acyl-coenzyme A: cholesterol acyltransferase inhibitors from Psoralea corylifolia.
Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes cholesterol esterification and plays important roles in intestinal absorption of cholesterol, hepatic production of lipoproteins and accumulation of cholesteryl ester within macrophages and smooth muscle cells. Ethanol extract of Psoralea corylifolia showed a significant inhibition of ACAT enzyme. Via bioactivity-guided fractionation of the ethanol extract of Psoralea corylifolia, two prenylated flavonoids were isolated. Their structures were determined as bavachin (1) and isobavachalcone (2) by spectroscopic analysis ((1)H-, (13)C-NMR, 2DNMR, and ESI-MS). The IC(50) values were 86.0 (1) and 48.0 (2) microM in the ACAT assay system using rat liver microsome. Compound 2 also decreased cholesteryl ester formations in HepG2 cells. In addition, this compound showed a noncompetitive type of inhibition of ACAT.
Choi
Jung Ho
JH
Natural Medicine Research Center, KRIBB, Daejeon 305-333, Korea.
Rho
Mun-Chual
MC
Lee
Seung Woong
SW
Choi
Ji Na
JN
Kim
Koanhoi
K
Song
Gyu Young
GY
Kim
Young Kook
YK
D000818:Animals; D045744:Cell Line, Tumor; D047188:Chalcones / Q000302:isolation & purification* / Q000494:pharmacology*; D002788:Cholesterol Esters / Q000138:chemical synthesis; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology*; D005419:Flavonoids / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D029907:Psoralea / Q000737:chemistry*; D051381:Rats; D012639:Seeds / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D047188:Chalcones; D002788:Cholesterol Esters; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007202:Indicators and Reagents; C459212:bavachin; C468754:isobavachalcone; D002785:Sterol O-Acyltransferase