Aged Garlic Extract Attenuates Inflammation and Retards the Development of Atherosclerosis in Apolipoprotein E-Knockout Mice

Recently we showed that aged garlic extract (AGE) retarded atherosclerosis in apolipoprotein E-knockout (ApoE-KO) mice. However, its mode of action remains to be elucidated. Since chronic inflammation is a key event for the development and promotion of atherosclerosis, we investigated whether AGE suppresses the inflammation in ApoE-KO mice. ApoE-KO mice were fed standard diet with or without 3% AGE for 12 weeks. At the end of treatment, aorta, liver and blood samples were collected. AGE feeding inhibited the progression of atherosclerotic lesion by 27% and reduced the circulating level of C-reactive protein, one of the inflammation markers, by 39% in ApoE-KO mice when compared with non-AGE feeding. In addition, AGE treatment decreased the protein level of tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, and reduced the activity of phospho-interleukin-1 receptor-associated kinase 4, an important mediator of toll-like receptor signaling pathway, in the liver by 49% and 53%, respectively, compared with ApoE-KO mice without AGE treatment. Moreover, AGE treatment nearly doubled the protein level of phospho-AMP-activated protein kinase (AMPK), which is involved in inhibition of TNF-α production in the liver. These results suggest that the anti-atherosclerotic effect of AGE involves the suppression of inflammation through the inhibition of TNF-α production by modulating AMPK activity in the liver.