Nutraceuticals and amyloid neurodegenerative diseases: a focus on natural phenols

Abstract

A common molecular feature of amyloid neurodegenerative diseases is the unfolding/misfolding of specific proteins/peptides which consequently become prone to aggregate into toxic assemblies and deposits that are the key histopathological trait of these pathologies. Apart from the rare early-onset familiar forms, these neurodegenerative diseases are age-associated disorders whose symptoms appear in aged people after long incubation periods. This makes the therapeutic approach particularly compelling and boosts the search for both early diagnostic tools and preventive approaches. In this last respect, natural compounds commonly present in foods and beverages are considered promising molecules, at least on the bench side. The so-called ‘nutraceutical approach’ suggests life-long healthy diets, particularly focusing on food molecules that are candidates to enter clinical trials as such or following a targeted molecular engineering. Natural phenols abundant in ‘healthy’ foods such as extra virgin olive oil, red wine, green tea, red berries and spices, appear particularly promising.

Keywords:

• Alzheimer’s disease
• Asian diet
• curcumin
• EGCG
• Ginkgo biloba
• Mediterranean diet
• nanoparticles
• oleocanthal
• oleuropein aglycone
• resveratrol

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• With the increase in life expectancy, cognitive decline and neurodegenerative amyloid diseases are becoming a major threat for the elderly.

• Diet and lifestyle are increasingly becoming known for their association with healthy aging and maintenance of cognitive performance.

• Reduced caloric intake, high nutrient density and prevalence of plant-derived foods are common characteristics of diets favoring an increased life expectancy and healthy physical and mental aging, such as the Mediterranean diet and certain Asian diets.

• There is much evidence to suggest that natural phenolic compounds enriched in plant-derived foods such as extra virgin olive oil, red wine, berries, green tea, herbs and spices are the major foodstuffs responsible for the beneficial effects of a healthy diet.

• Results from many studies carried out in vitro and in animal models and from more limited epidemiological analysis, case studies and clinical trials support the potential use of some natural phenols including oleuropein aglycone, resveratrol, curcumin, epigallocatechin gallate and Ginkgo biloba extracts against cognitive decline and amyloid neurodegenerative diseases such as Alzheimer’s disease.

• Research efforts are devoted to increasing the bioavailability (especially across the blood–brain barrier) of these compounds. Promising approaches exploit encapsulation in hydrophobic nanoparticles, molecule engineering, association with other natural or synthetic compounds and alternative administration routes.

• Clinical trials are hampered by several difficulties including recruitment of a sufficient number of subjects corresponding to the inclusion criteria, maintenance of a strict adherence to the protocol for a long period (at least 12 months) by aged and sometimes already cognitively impaired subjects, and defining and applying ingestion conditions to maximize drug bioavailability.

• Some clinical trials testing resveratrol, curcumin, epigallocatechin gallate and, apart from these, Ginkgo biloba extracts against cognitive impairment and amyloid neurodegeneration are ongoing or already completed, though in most cases the results of these studies are not yet available.

• The growing interest of the community toward the nutraceutical approach to improve health is expected to increase the efforts on the bed side of the research, possibly providing conclusive results about the effectiveness of some of these phenols in the coming years.