Lipid-lowering efficacy of 3,4-di(OH)-phenylpropionic L-leucine in high-cholesterol fed rats

• Published in: Journal of biochemical and molecular toxicology Vol. 19; no. 1; pp. 25 - 31
• Main Authors: Kim, Soon-Ja, Bok, Song-Hae, Lee, SangKu, Lee, Mi-Kyung, Park, Yong Bok, Kim, Hye-Jin, Choi, Myung-Sook
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.01.2005
• Subjects: 3,4‐Di(OH)‐hydrocinnamate; 3,4‐Di(OH)‐phenylpropionic; 4-Di(OH)-hydrocinnamate; 4-Di(OH)-phenylpropionic; Animal Feed; Animals; Caffeic Acids - chemistry; Caffeic Acids - pharmacology; Cholesterol, Dietary - administration & dosage; Cholesterol, Dietary - pharmacology; Feces - chemistry; high-Cholesterol Diet; Hydroxymethylglutaryl CoA Reductases - metabolism; L-Leucine amide; Leucine - analogs & derivatives; Leucine - chemistry; Leucine - pharmacology; Lipid Metabolism; Lipids - blood; Liver - drug effects; Liver - metabolism; Male; Molecular Structure; Organ Size - drug effects; Rats; Rats, Sprague-Dawley; Sterols - metabolism; Weight Gain - drug effects
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.20054

A preliminary study revealed that 3,4‐di(OH)‐hydrocinnamate (HC), a polyphenolic compound, lowered the plasma lipids in high‐cholesterol fed rats. Accordingly, this study was designed to test the lipid‐lowering efficacy of a synthetic derivative, 3,4‐di(OH)‐phenylpropionic (L‐leucine) amide (PPLA), in rats fed a high‐cholesterol (1%, wt/wt) diet. As such, HC or PPLA was given as supplement to a high‐cholesterol diet for 6 weeks at a dose of 0.137 mmol/100 g diet. The supplementation of HC and PPLA significantly lowered the plasma and hepatic cholesterol and triglyceride levels compared to the control group. The activities of hepatic HMG‐CoA reductase (164 ± 9.12 and 124.74 ± 17.09 pmol/min/mg protein vs. 245.41 ± 13.01 pmol/min/mg protein, p < 0.05) and ACAT (411.49 ± 11.48 and 334.35 ± 17.68 pmol/min/mg protein vs. 490.41 ± 16.69 pmol/min/mg protein, p < 0.05) were significantly lower in the HC‐ and PPLA‐supplemented groups than in the control group. However, PPLA was more effective in inhibiting the enzyme activities than HC. The excretion of neutral sterol was significantly higher in HC‐ and PPLA‐supplemented groups than in the control group. Therefore, these results indicate that PPLA, a leucine‐attached version of HC, exhibited a similar significant hypocholesterolemic effect to HC in rats fed a high‐cholesterol diet. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:25–31, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20054