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

Background: Combination therapy plays an important role in the management of cardiovascular disease (CVD). Objectives: 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. Materials and Methods: 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). Results: 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. Conclusions: 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.