Therapeutic potential of ferulic acid and its derivatives in Alzheimer’s disease—A systematic review

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily caused by accumulation of amyloid-beta (Aβ) peptide extracellularly and neurofibrillary tangles intracellularly. Recently, it has been shown that oxidative stress and mitochondrial dysregulation play an important role in pathology of AD. Therefore, modulating various targets such as Aβ aggregation, neuro-inflammation, and oxidative stress, genetic factors such as Apolipoprotein E gene (ApoE) are some of the ways to manage AD. Studying the natural products which can act as multifunctional agents could be key toward discovering new therapeutics. Ferulic acid (FA) represents one such natural product, which has exhibited great potential in this regard.Found in the plant cell walls, FA is an antioxidant, free radical scavenger with antiinflammatory activity. Taking this into consideration, over the years, various derivatives have been reported as anti-AD molecules based on structure of FA. The present review explores the role of FA and its derivatives as therapeutic agents in AD.

Network Pharmacology-Based Strategy to Investigate the Pharmacologic Mechanisms of Coptidis Rhizoma for the Treatment of Alzheimer's Disease

“…Ferulic acid (FA) may repair the pathological damage of AD by improving the imbalance of mitochondrial division-fusion kinetics, interfering with oxidative stress and inflammation caused by Aβ aggregation, and then regulating the biological pathways involved in apoptotic programmed cell death (Wang Q. et al, 2019 ; Wang E. J. et al, 2021 ). Similarly, chlorogenic acid can control many pathophysiological characteristics of neurodegenerative diseases by improving mitochondrial dysfunction, reducing neuroinflammation and Aβ protein aggregation, and antioxidant stress (Phadke et al, 2021 ). The improvement of dysfunction, reduction of oxidative stress, and apoptosis may provide a direction for treating AD.…”

Interactions of Curcumin’s Degradation Products with the Aβ42 Dimer: A Computational Study

“…The degradation products of curcumin have a higher solubility as compared to curcumin and may therefore be appropriate candidate for anti-AD therapeutics . As a matter of fact, ferulic acid can protect neurons against Aβ-induced oxidative stress, which plays a significant role in the pathology of AD. − Additionally, ferulic acid can dose-dependently prevent both formation and extension of Aβ oligomers and destabilize Aβ fibrils . An in vitro study showed that vanillin has acetylcholinesterase inhibitory activities, leading to the restoration of acetylcholine levels in diseased brains leading to an improvement in memory function .…”

Development of Semisynthetic Apoptosis-Inducing Agents Based on Natural Phenolic Acids Scaffold: Design, Synthesis and In-Vitro Biological Evaluation

“…Caffeic acid and its different derivatives were reported to possess many biological activities such as immunostimulants [ 9 , 10 , 11 , 12 ], antibacterial [ 13 , 14 ], anti-inflammatory [ 15 ], cardio protective [ 15 , 16 ], anti-atherosclerotic [ 9 , 17 ], antidiabetic [ 15 , 18 ], antiproliferative [ 19 , 20 ], hepatoprotective [ 21 ], anticancer [ 9 , 13 , 14 , 15 , 22 , 23 , 24 ], and Alzheimer’s disease [ 25 ].…”

“…Ferulic acid has been used in healthy food and nutrition restoratives due to its well-known antioxidant properties, and due to this biological effect, it can be used in Alzheimer’s disease [ 25 , 26 ]. It is highly recommended for diabetic patients [ 27 ].…”

“…The aforementioned biological activities are achieved through a variety of mechanisms; the anticancer activity of both CA and FA is exerted by two mechanisms, acting as primary antioxidants that eliminate reactive oxygen species (ROS) and as secondary antioxidants (pro-oxidants) preventing the splitting of peroxides by metal ion chelation (iron and copper) [ 37 , 38 ]. Thus, inhibiting oxidative degradation of essential biological molecules (lipids, amino acids, polyunsaturated fatty acids and DNA bases) and preventing the formation of cellular lesions [ 25 , 39 , 40 , 41 , 42 ].…”