Neuroprotective Properties of Ferulic Acid in Preclinical Models ofAlzheimer’s Disease: A Systematic Literature Review

Background: Alzheimer's disease (AD) is one of the most common diseases in the elderly, with a high incidence of dementia. The pathogenesis of AD is complex, and there is no unified conclusion and effective treatment in the clinic. In recent years, with the development of traditional Chinese medicine (TCM), researchers put forward the idea of prevention and treatment of AD based on TCM according to the characteristics of multi- target of TCM. Ferulic acid (FA), also known as 3-methoxy-4-hydroxycinnamic acid, is an active ingredient in TCM that inhibits β-amyloid (Aβ) aggregation and has antioxidant and anti-inflammatory effects. FA derivatives have been reported to have low toxicity, high biological activity, and high blood-brain barrier permeability. However, the multitarget of FA in the treatment of AD has not been systematically elucidated. Objectives: In this systematic review, we aimed to comprehensively assess the neuroprotective effects of FA and its derivatives on in vitro and in vivo AD models. Methods: We searched PubMed, Chinese National Knowledge Infrastructure (CNKI), Baidu Academic, and Wanfang databases for relevant pre-clinical studies until November 2021. Results: We identified studies that evaluated the efficacy of FA and its derivatives using relevant keywords. 864 studies were included, of which 129 were found in PubMed, 111 in CNKI, 454 in Baidu Academic, and 170 in Wanfang. Due to duplication between databases, and after applying the exclusion and inclusion criteria, 43 articles were selected. Thereafter, the abstracts of the 43 articles were reviewed. Finally, 21 articles were included in this review, including 11 in vivo, 5 in vitro, and 5 in vivo and in vitro studies. Conclusion: Previous studies have shown that FA or its derivatives have multiple therapeutic effects on AD models and can improve the symptoms of AD and resistance of AD cell models. FA and its derivatives have anti-Aβ aggregation, antioxidant, antiinflammatory, and other effects and are potential drugs for the multi-targeted treatment of AD. The result of our study showed that FA and its derivatives have significant therapeutic effects on animal and cell models of AD, suggesting that they may be potential therapeutic drugs for patients with AD.