In vitro inhibition of diacylglycerol acyltransferase by prenylflavonoids from Sophora flavescens.
Four prenylflavonoids, kurarinone ( 1), a chalcone of 1, kuraridin ( 2), kurarinol ( 3), kushenol H ( 4) and kushenol K ( 5) isolated from the roots of Sophora flavescens were investigated for their inhibitory effects on diacylglycerol acyltransferase (DGAT). The flavonoids inhibited DGAT activity in a dose-dependent manner with IC50 values of 10.9 microM ( 1), 9.8 microM ( 2), 8.6 microM ( 3), 142.0 microM ( 4) and 250 microM ( 5). The prenylflavonoids without C3-OH ( 1, 2, 3) showed stronger inhibition than those with C3-OH ( 4, 5). On the other hand, flavonoids without side chains (hesperetin, naringenin, quercetin and kaempferol) did not inhibit the enzyme activity at a final concentration of 800 microM. These data suggest that the lavandulyl side chain and the position of the hydroxy group are important for high DGAT inhibitory activity. Compound 1 also inhibited de novo synthesis of triacylglycerol (TG) in Raji cells.
Chung
Mi Yeon
MY
Laboratory of Lipid Metabolism, Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea.
Rho
Mun-Chual
MC
Ko
Jeong Suk
JS
Ryu
Shi Yong
SY
Jeune
Kyung Hee
KH
Kim
Koanhoi
K
Lee
Hyun Sun
HS
Kim
Young Kook
YK
D000217:Acyltransferases / Q000096:biosynthesis / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000201:enzymology; D051048:Diacylglycerol O-Acyltransferase; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005419:Flavonoids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots; D017368:Protein Prenylation; D029909:Sophora; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010936:Plant Extracts; D000217:Acyltransferases; C494881:DGAT1 protein, human; D051048:Diacylglycerol O-Acyltransferase