Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a tangle-shaped accumulation of beta-amyloid peptide fragments and Tau protein in brain neurons. The pathophysiological mechanism involves the presence of Aβ-amyloid peptide, Tau protein, oxidative stress, and an exacerbated neuro-inflammatory response. This review aims to offer an updated compendium of the most recent and promising advances in AD treatment through the administration of phytochemicals. The literature survey was carried out by electronic search in the following specialized databases PubMed/Medline, Embase, TRIP database, Google Scholar, Wiley, and Web of Science regarding published works that included molecular mechanisms and signaling pathways targeted by phytochemicals in various experimental models of Alzheimer’s disease in vitro and in vivo. The results of the studies showed that the use of phytochemicals against AD has gained relevance due to their antioxidant, anti-neuroinflammatory, anti-amyloid, and anti-hyperphosphorylation properties of Tau protein. Some bioactive compounds from plants have been shown to have the ability to prevent and stop the progression of Alzheimer’s.

An updated overview of anticancer effects of alternariol and its derivatives: underlying molecular mechanisms

“…MAPKs are involved in the phosphorylation of JNK, ERK and p38 which regulate the expression of MSK 1/2 and then p65 ( Xie et al, 2019 ; Garzoli et al, 2022 ; Li et al, 2023 ). Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are also key enzymes involved in inflammation and cell stress, being NO an important regulator of COX-2 expression and activity ( Sharifi-Rad et al, 2022c ; Li et al, 2023 ). AOH showed to lead to the phosphorylation of cAMP response element-binding (CREB) and increased the expression of COX-2 ( Bansal et al, 2019 ).…”

Phytochemical Interactions with Calmodulin and Critical Calmodulin Binding Proteins Involved in Amyloidogenesis in Alzheimer’s Disease

“…Several studies have reported on BACE1 inhibiting phytochemicals that also bind to and inhibit acetylcholinesterase, another key target in AD [ 52 , 53 , 54 ]. There are arguments that such multi-directed agents may offer unique benefits over single target treatments but here we are specifically interested in what these phytochemicals can yield about the targeting BACE1 [ 55 ]. The goal here is to show that multiple phytochemicals bind to and inhibit the CaMBP BACE1 in support of the primary premise of this review that CaM and its targets are central to the onset and progression of AD and a diversity of phytochemicals exert their AD-related therapeutic effects via them.…”

A comprehensive review on traditional uses, phytochemistry and pharmacological properties of Paeonia emodi Wall. ex Royle: current landscape and future perspectives

“…Brain functions are influenced by poor nutrition, stress and lack of movement, but also by natural cellular oxidation processes [19,106,[154][155][156][157]. In addition to improving lifestyle, the brain and memory can benefit from the stimulating input of nature due to plants with a beneficial effect on brain functions [158][159][160]. Recent research studied the effects of a Paeonia emodi Wall.…”