Anticholesterolemic effect of 3,4-di(OH)-phenylpropionic amides in high-cholesterol fed rats.
Two amide synthetic derivatives of 3,4-di(OH)-hydrocinnamate (HC), 3,4-dihydroxyphenylpropionic (l-serine methyl ester) amide (E030) and 3,4-dihydroxyphenylpropionic (l-aspartic acid) amide (E076), were investigated to compare their lipid-lowering efficacy with HC. Male rats were fed a 1 g/100 g high-cholesterol diet for 6 weeks with supplements of either clofibrate (0.02%, w/w), HC (0.025%, w/w), E030 (0.039%, w/w) or E076 (0.041%, w/w). The clofibrate supplement was used as a positive control for the lipid-lowering efficacy. The food intakes and body weight gains were not significantly different among the groups. The plasma and hepatic cholesterol and triglyceride levels were lower in clofibrate, HC, E030, and E076-supplemented groups compared to the control group. The supplementation of HC and its amide derivatives was as effective as clofibrate in increasing the ratio of HDL-cholesterol to total plasma cholesterol and reducing the atherogenic index (AI). The hepatic cholesterol level in the HC and E076 groups was significantly lower than that in the clofibrate group. The hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA reductase) and acyl-CoA:cholesterol acyltransferase (ACAT) activities were significantly lower in the all test groups than in the control group. The excretion of neutral sterol was significantly higher in the HC, E030, and E076-supplemented groups compared to the control group. The plasma AST and ALT activities, indirect indexes of hepatic toxicity, were significantly lower in the HC, E030, and E076-supplemented groups than in the control group. Accordingly, the current results suggest that E030 and E076, two amide synthetic derivatives of HC, are effective in lowering lipid activity.
Kim
Soon-Ja
SJ
Department of Food Science and Nutrition, Kyungpook National University, 702-701 Daegu, South Korea.
Bok
Song-Hae
SH
Lee
Sangku
S
Kim
Hye-Jin
HJ
Lee
Mi-Kyung
MK
Park
Yong Bok
YB
Choi
Myung-Sook
MS
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D002109:Caffeic Acids / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D002934:Cinnamates / Q000494:pharmacology / Q000627:therapeutic use; D002994:Clofibrate / Q000494:pharmacology / Q000627:therapeutic use; D005243:Feces / Q000737:chemistry; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D006937:Hypercholesterolemia / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D008055:Lipids / Q000096:biosynthesis / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D002785:Sterol O-Acyltransferase / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
C469894:3,4-di(OH)-cinnamate; C509987:3,4-dihydroxyphenylpropionic (aspartic acid) amide; C509986:3,4-dihydroxyphenylpropionic (serine methyl ester) amide; D000924:Anticholesteremic Agents; D002109:Caffeic Acids; D002791:Cholesterol, Dietary; D002934:Cinnamates; D008055:Lipids; D014280:Triglycerides; D001224:Aspartic Acid; D012694:Serine; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002785:Sterol O-Acyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002994:Clofibrate