Caffeic acid protects against atherosclerotic lesions and cognitive decline in ApoE^-/- mice

Caffeic acid has been indicated to benefit cholesterol balance, but the effect of pure caffeic acid on atherosclerosis in vivo has not been tested. Given that atherosclerosis and Alzheimer's disease share common features including distracted lipid balance and chronic inflammation, the concurrent effects of caffeic acid on atherosclerotic lesions and cognitive decline were explored here by using the ApoE^-/- mice model. A two months' administration of 20 mg/kg caffeic acid or saline was given once two days intraperitoneally to 5-month-old female ApoE^-/- mice. We found that the caffeic acid treatment reduced the atherosclerotic lesions in the whole aorta and aortic sinus of the resulting 7-month-old ApoE^-/- mice by roughly 50%, compared with the saline control. Meanwhile, the cognitive decline of treated mice were significantly alleviated, as measured by Y-maze and Morris water maze tasks. A reduced accumulation of β-amyloid in the hippocampus was also observed. These effects were associated with elevated serum HDL-c concentration, upregulated ABCA1 and ABCG1 mRNA levels, as well as decrease local inflammation and reduced levels of serum pro-inflammatory cytokines including TNF-α, IL-6 and MCP-1. These obtained results suggested the preventive and therapeutic potential of caffeic acid against atherosclerosis and Alzheimer's disease during aging.