Abstract
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