Ferulic acid alleviates high fat diet-induced cognitive impairment by inhibiting oxidative stress and apoptosis

Cognitive impairment has become a major public health problem. Growing evidence suggests that high-fat diet (HFD) can cause cognitive dysfunction and increase the risk of dementia. However, effective treatment for cognitive impairment is not available. Ferulic acid (FA) is a single phenolic compound with anti-inflammatory and antioxidant properties. Nevertheless, its role in regulating learning and memory in HFD-fed mice and the underlying mechanism remains unclear. In this study, we aimed to identify the neuroprotective mechanisms of FA in HFD induced cognitive impairment. We found that FA improved the survival rate of HT22 cells treated with palmitic acid (PA), inhibited cell apoptosis, and reduced oxidative stress via the IRS1/PI3K/AKT/GSK3 beta signaling pathway; Furthermore, FA treatment for 24 weeks improved the learning and memory of HFD-fed mice and decreased hyperlipidemia. Moreover, the expression of Nrf2 and Gpx4 proteins were decreased in HFD-fed mice. After FA treatment, the decline of these proteins was reversed. Our study showed that the neuroprotective effect of FA on cognitive impairment was related to the inhibition of oxidative stress and apoptosis and regu- lation of glucose and lipid metabolism. These findings suggested that FA can be developed as a potential agent for the treatment of HFD-induced cognitive impairment.

Automated summary

Cognitive impairment is a major public health problem, and a high-fat diet has been linked to cognitive dysfunction and increased risk of dementia. However, there is currently no effective treatment available. Ferulic acid, a phenolic compound with anti-inflammatory and antioxidant properties, shows promise in protecting against cognitive impairment caused by a high-fat diet. It improves cell survival, inhibits apoptosis, and reduces oxidative stress via the IRS1/PI3K/AKT/GSK3 beta signaling pathway. In addition, treatment with ferulic acid for 24 weeks improves learning and memory in high-fat diet-fed mice and decreases hyperlipidemia. These findings suggest that ferulic acid could be developed as a potential treatment for high-fat diet-induced cognitive impairment.