Combination of Ezetimibe and Garlic Reduces Serum Lipids and Intestinal Niemann-Pick C1-like 1 Expression More Effectively in Hypercholesterolemic Mice

Combination therapy plays an important role in the management of cardiovascular disease (CVD). The aim of this experiment was to study the influence of garlic combined with ezetimibe on lipid profile as well as intestinal Niemann-Pick C1-like 1 (NPC1L1) expression in normal and hypercholesterolemic mice. A total of 40 mice were randomly divided into five groups: Group 1: hypercholesterolemic group (received 2% w/w cholesterol + 0.5% w/w cholic acid in their diet), Group 2: garlic group (hypercholesterolemic diet + 4% w/w garlic extract), Group 3: ezetimibe group (hypercholesterolemic diet + 0.005% w/w ezetimibe), Group 4: combination group (hypercholesterolemic diet + 0.005% w/w ezetimibe + 4% w/w garlic) and Group 5: control (chow only). Serum low-density lipoprotein-cholesterol (LDL-C) and total cholesterol (TC) levels were significantly decreased in ezetimibe, garlic (both P < 0.05), and combination groups (P < 0.001). Also, triglycerides and very low-density lipoprotein-cholesterol (VLDL-C) were significantly lower in garlic and combination groups (P < 0.05). Liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were also significantly decreased in garlic, ezetimibe (both P < 0.05) and combination groups (P < 0.001) in comparison with hypercholesterolemic animals. Analysis of semi quantitative RT-PCR results showed that the levels of NPC1L1 was also significantly less (P < 0.01) in the garlic, ezetimibe, and combination groups (P < 0.001) compared with the controls. Based on the results, the combination of garlic and ezetimibe can lower serum lipids and liver enzymes more effectively in hypercholesterolemic mice. This experiment revealed that a possible mechanism for the beneficial effects of garlic and ezetimibe combination in lowering plasma LDL-C and TC is inhibition of intestinal cholesterol absorption. More research might be necessary to determine the efficacy and the exact mechanism of this co-administration.