Abstract
Cognitive impairment, also known as cognitive decline, can occur gradually or suddenly and can be temporary or more permanent. It represents an increasingly important public health problem and can depend on normal aging or be linked to different neurodegenerative disorders, including Alzheimer’s disease (AD). It is now well-established that lifestyle factors including dietary patterns play an important role in healthy aging as well as in the prevention of cognitive decline in later life. Among the natural compounds, dietary polyphenols including phenolic acids have been recently the focus of major attention, with their supplementation being associated with better cognitive status and prevention of cognitive decline. Despite their therapeutic potential, human studies investigating the relation between phenolic acids intake and cognitive outcomes are rather scarce. In this review, we provide preclinical evidence that different dietary polyphenols such as rosmarinic acid, ellagic acid, and cinnamic aldehyde can exert neuroprotective and pro-cognitive activities through different molecular mechanisms including the modulation of pro-oxidant and antioxidant machinery as well as inflammatory status. Future and more numerous in vivo studies are needed to strengthen the promising results obtained at the preclinical level. Despite the excellent pharmacokinetic properties of phenolic acids, which are able to be accumulated in the brain at pharmacologically relevant levels, future studies should also identify which among the different metabolites produced as a consequence of phenolic acids’ consumption may be responsible for the potential neuroprotective effects of this subgroup of polyphenols.
Highlights
Growing evidence supports the hypothesis that dietary factors may play a role in healthy aging, including a protective effect against age-related cognitive decline [1]
The results showed that the treatment with cinnamic aldehyde significantly reverted Aβ-induced toxicity, while adenosine, NMDA, and dantrolene inhibited the neuroprotection exerted by this natural compound
In conclusion, recent evidence suggests that phenolic acids may exert neuroprotective effects targeting multiple cellular pathways involved in the pathophysiology of cognitive disorders
Summary
Growing evidence supports the hypothesis that dietary factors may play a role in healthy aging, including a protective effect against age-related cognitive decline [1]. The most common group of polyphenolic compounds is represented by flavonoids and the main subclasses flavonols, flavones, flavanones, flavan-3-ols, anthocyanidins, and isoflavones, largely contained in fruits and vegetables [3] The potential of these molecules in preventing and/or counteracting neurodegenerative phenomena has been recently considered [4–6]. Other classes of polyphenols largely investigated for their potential role in neurodegenerative diseases include stilbenes (such as resveratrol, contained in red wine), tyrosol (such as oleuropein, contained in olive oil), and curcuminoid (such as curcumin, contained in turmeric) [2] Another non-flavonoid group of polyphenols includes phenolic acids, a heterogeneous family of polyphenols commonly consumed, largely underrated, and far less investigated concerning their potential effects against neurodegenerative diseases [2]. Hydroxybenzoic acids include in their structure a C6-C1 carbon backbone with methoxylations and hydroxylations at the aromatic ring: the main molecules of interest include gallic, p-hydroxybenzoic, vanillic, syringic, and protocatechuic acids; the main dietary sources of these compounds are certain cereals (i.e., bran, grain brown rice, and derivatives, such as beer), olive oil, tea (despite some differences between types and fermentation), some fruits (i.e., cherries, plums, and gooseberries among others), and red wine [13]
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