Mei Zhengrong, Hong Ye, Yang Haiyi, Cai Shihong, Hu Yujun, Chen Qibo, Yuan Zhongwen, Liu Xixia
Department of Pharmacy, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, 510150, PR China.
Department of Pharmacy, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, 510440, PR China.
Eur J Pharmacol. 2023 May 5;946:175642. doi: 10.1016/j.ejphar.2023.175642. Epub 2023 Mar 3.
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/GSK3β 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 regulation 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.
认知障碍已成为一个主要的公共卫生问题。越来越多的证据表明，高脂饮食（HFD）会导致认知功能障碍并增加患痴呆症的风险。然而，目前尚无针对认知障碍的有效治疗方法。阿魏酸（FA）是一种具有抗炎和抗氧化特性的单一酚类化合物。然而，其在调节高脂饮食喂养小鼠的学习和记忆方面的作用及其潜在机制仍不清楚。在本研究中，我们旨在确定阿魏酸在高脂饮食诱导的认知障碍中的神经保护机制。我们发现，阿魏酸提高了经棕榈酸（PA）处理的HT22细胞的存活率，抑制了细胞凋亡，并通过IRS1/PI3K/AKT/GSK3β信号通路降低了氧化应激；此外，阿魏酸治疗24周改善了高脂饮食喂养小鼠的学习和记忆，并降低了高脂血症。此外，高脂饮食喂养小鼠中Nrf2和Gpx4蛋白的表达降低。阿魏酸治疗后，这些蛋白的下降得到逆转。我们的研究表明，阿魏酸对认知障碍的神经保护作用与抑制氧化应激和细胞凋亡以及调节糖脂代谢有关。这些发现表明，阿魏酸可开发成为治疗高脂饮食诱导的认知障碍的潜在药物。
