The hypocholesterolemic effect of tomato juice has been investigated in an 
intervention study with rats, along with the possible inhibition effect of 
bioactive tomato compounds binding to the HMGCR enzyme. Two experimental groups 
(n = 8 Sprague-Dawley rats) were fed ad libitum for five weeks, with water or 
tomato juice provided to the control and intervention groups, respectively. 
Total, LDL and HDL cholesterol, and total triglycerides were analysed in plasma, 
and the lycopene content and the expression and activity of the enzyme HMGCR 
were determined in liver samples. A computational molecular modelling was 
carried out to determine the interactions between HMGCR and lycopene, 
chlorogenic acid and naringenin. Total, LDL and HDL cholesterol were 
significantly lower in the intervention group after the intake of tomato juice. 
In addition, a significant reduction in HMGCR activity was observed, although 
this was not accompanied by changes in gene expression. The molecular modelling 
showed that components of tomato can bind to the active site of the enzyme and 
compete with the ligand HMGCoA. Lycopene, from tomato juice, accumulates in the 
liver and can inhibit the activity of the rate-limiting enzyme of cholesterol 
biosynthesis, HMGCR.