Hypocholesterolemic and antioxidant properties of 3-(4-hydroxyl)propanoic acid derivatives in high-cholesterol fed rats

The purpose of the present study was to evaluate the in vivo efficacy of two cinnamic acid synthetic derivatives (allyl 3-[4-hydroxyphenyl]propanoate; HPP304, 1-naphthyl-methyl 3-[4-hydroxyphenyl]propanoate; HPP305) in high-cholesterol fed rats and compare their actions to that of cinnamic acid. Cinnamic acid and its synthetic derivatives were supplemented with a high-cholesterol diet for 42 days at a dose of 0.135 mmol/100g of diet. The supplementation of HPP304 and HPP305 significantly lowered cholesterol and triglyceride levels in the plasma and liver with a simultaneous increase in the HDL-cholesterol concentration, whereas cinnamic acid only lowered the plasma cholesterol concentration. Cinnamic acid lowered hepatic HMG-CoA reductase activity in high-cholesterol fed rats, however, its synthetic derivatives (HPP304 and HPP305) did not affect HMG-CoA reductase activity compared to the control group. Instead, the HPP304 and HPP305 supplements significantly lowered hepatic acyl coenzyme A:cholesterol acyltransferase activity and increased the fecal bile acid. The SOD activity of the erythrocytes and liver was not different between the groups, however, the activities of CAT and GSH-Px, and the level of GSH in the erythrocytes were significantly higher in the HPP304 and HPP305 groups than in the control group. On the other hand, the activities of CAT and GSH-Px, and the level of malondialdehyde in the liver were significantly lower in the HPP304 and HPP305 groups. The antioxidant activities of these cinnamic acid synthetic derivatives were similar to the cinnamic acid in the high-cholesterol fed rats. In addition, HPP304 and HPP305 lowered amniotransferase activity in the plasma. These results suggest that two cinnamic acid synthetic derivatives (HPP304 and HPP305) exert lipid-lowering action and antioxidant properties without hepatotoxicity in high-cholesterol fed rats.