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 b-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 inflamma-tion and reduced levels of serum pro-inflammatory cytokines including TNF-a, 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.(c) 2022 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/lice nses/by-nc-nd/4.0/).

Automated summary

In this study, the effects of pure caffeic acid on atherosclerosis and cognitive decline were investigated using the ApoE-/- mice model. The results showed that treatment with caffeic acid significantly reduced atherosclerotic lesions in the aorta and aortic sinus of the mice compared to the control group. Additionally, caffeic acid treatment alleviated cognitive decline and reduced the accumulation of b-amyloid in the hippocampus. These effects were associated with increased HDL-c concentration, upregulated expression of ABCA1 and ABCG1 genes, decreased inflammation, and reduced levels of pro-inflammatory cytokines in the serum.