Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes

Abstract

Alzheimer’s disease (AD) is a chronic, complex neurodegenerative disorder mainly characterized by the irreversible loss of memory and cognitive functions. Different hypotheses have been proposed thus far to explain the etiology of this devastating disorder, including those centered on the Amyloid-β (Aβ) peptide aggregation, Tau hyperphosphorylation, neuroinflammation and oxidative stress. Nonetheless, the therapeutic strategies conceived thus far to treat AD neurodegeneration have proven unsuccessful, probably due to the use of single-target drugs unable to arrest the progressive deterioration of brain functions. For this reason, the theoretical description of the AD etiology has recently switched from over-emphasizing a single deleterious process to considering AD neurodegeneration as the result of different pathogenic mechanisms and their interplay. Moreover, much relevance has recently been conferred to several comorbidities inducing insulin resistance and brain energy hypometabolism, including diabetes and obesity. As consequence, much interest is currently accorded in AD treatment to a multi-target approach interfering with different pathways at the same time, and to life-style interventions aimed at preventing the modifiable risk-factors strictly associated with aging. In this context, phytochemical compounds are emerging as an enormous source to draw on in the search for multi-target agents completing or assisting the traditional pharmacological medicine. Intriguingly, many plant-derived compounds have proven their efficacy in counteracting several pathogenic processes such as the Aβ aggregation, neuroinflammation, oxidative stress and insulin resistance. Many strategies have also been conceived to overcome the limitations of some promising phytochemicals related to their poor pharmacokinetic profiles, including nanotechnology and synthetic routes. Considering the emerging therapeutic potential of natural medicine, the aim of the present review is therefore to highlight the most promising phytochemical compounds belonging to two major classes, polyphenols and monoterpenes, and to report the main findings about their mechanisms of action relating to the AD pathogenesis.

RETRACTED ARTICLE: Polyphenols from Conyza dioscoridis (L.) ameliorate Alzheimer’s disease- like alterations through multi-targeting activities in two animal models

“…The effect of DON used as a reference drug documents the effect of PCDE on Aβ and tau protein [64][65][66]. Polyphenols decrease amyloid, tau, α-syn, and synphilin-1 deposits, by inhibition of their formation or by disaggregation of them [67][68][69]. PCDE is rich in many phenolic compounds which may induce disaggregation of aggregated p-tau and amyloid.…”

Anti-Cholinesterase and Anti-α-Amylase Activities and Neuroprotective Effects of Carvacrol and p-Cymene and Their Effects on Hydrogen Peroxide Induced Stress in SH-SY5Y Cells

“…In light of previous studies that highlight standard features between AD and T2DM and consider medicinal plants or their constituents as potential neuroprotective agents [ 21 , 33 ] and enzymatic inhibitors [ 17 , 21 ], and considering that, to the best of our knowledge, there are no studies on natural substances that correlate neuroprotective effects with possible activity against enzymes involved in diabetes, the aims of this study were: (1) to evaluate the possible effects of carvacrol and its precursor p -cymene on AChE, BChE, and α-amylase activities; (2) to study the potential of these monoterpenes as neuroprotective agents in hydrogen-peroxide-induced stress in SH SY5Y cells, considering that, in neurodegenerative diseases, oxidative brain damage is often present.…”

Epigallocatechin-3-gallate and resveratrol attenuate hydrogen peroxide induced damage in neuronal cells

“…Epigallocatechin gallate and resveratrol are potent antioxidant molecules, and the literature contains abundant research exploring their benefi ts against various diseases (22,23). Due to their antioxidant potency, these two compounds have been intensively investigated as anti-carcinogenic compounds; in addition, their neuroprotective properties are also the ongoing subject of research (24,25). In the present study, we evaluated the capacity of EGCG and resveratrol to prevent H 2 O 2 -induced toxicity in SH-SY5Y cells.…”