Fruits and vegetables may hold the key to treating Alzheimer’s

Alzheimer's causes steady disintegration of personality and loss of connection with the world. Credit: Gerd Altman, CC0

Flavonoids are found in many foods and could lead to new treatments for Alzheimer’s disease

Natural compounds called flavonoids and modified derivatives might treat  Alzheimer’s disease by halting its progress. Om Silakari and colleagues at Punjabi University in India report encouraging results from cell-based and whole animal trials in the journal Bioorganic & Medicinal Chemistry. Their approach is to take some natural flavonoids then investigate the effects of a range of chemical modifications.

Alzheimer’s disease is one of society's major medical challenges. It affects more than 40 million people worldwide, bringing memory loss and dementia that progressively destroys its victims' personalities and can wreak havoc in family life.

Alzheimer's disease is a neurodegenerative  disorder associated with a selective loss of nerve cells that release the neurotransmitter acetylcholine. The reduction in acetylcholine is attributed to the action of an enzyme called acetylcholinesterase (AChE). Chemical reactions called oxidation reactions, leading to "oxidative stress", are considered to be another major cause of nerve cell death in Alzheimer's disease. Oxidative imbalance and oxidative stress also promote the production  of tangles of protein called beta-amyloid plaques. Various oxidation reactions also produce functional alterations in lipids, proteins, and DNA. "Our work opens up the possibility of attacking these different targets all together,"explains Silakari.

The ability to fight Alzheimer's on several fronts simultaneously relies on three distinct properties of the flavonoid compounds. They can inhibit the activity of the AChE enzyme responsible for depleting acetylcholine in the brain. They also have significant antioxidant activity, offering protection against the oxidative damage which aggravates the disease. And they inhibit a chemical process called glycation that promotes changes involved in the cross-linking of proteins to form the beta-amyloid plaques.

The researchers tested the effects of flavonoids in mice suffering from memory defects that serve as a model for key aspects of Alzheimer’s disease. The flavonoid treatment significantly improved the ability of the mice to remember their way around a maze—a standard procedure for testing drugs for beneficial effects on memory disorders—showing the potential of a flavonoid-based treatment.

“Our work establishes the potency of these molecules that target different molecular pathways rather than just one,” says Silakari. Of course, the mice are only an approximate model of the problems found in Alzheimer’s disease.

A lead compound is a molecule that shows sufficient potential as a treatment for it to be worked on much more and eventually tested in clinical trials. Silakari believes their results suggest that flavonoids and flavonoid-based compounds “might be promising lead compounds as potential polyfunctional anti- Alzheimer’s agents.”

Silakari also highlights the significance of flavonoids as natural components of many foods, especially those fruits, vegetables, and teas that are commonly promoted as good for optimal health. “Our work also highlights the significance of healthy dietary habits in managing neurological disorders,” he adds.

Singh, M. et al.: "Exploration of multi-target potential of chromen-4-one based compounds in Alzheimer's disease: Design, synthesis and biological evaluations," Bioorganic & Medicinal Medicine (2017)