Combining two dietary compounds found in green tea and carrots reversed cognitive deficits, lowered the accumulation of toxic amyloid beta, and reduced brain inflammation and oxidative damage in a mouse model of Alzheimer’s disease, a study reports.
The study, “Combined treatment with the phenolics (−)-epigallocatechin-3-gallate and ferulic acid improves cognition and reduces Alzheimer-like pathology in mice,” appeared in the Journal of Biological Chemistry.
EGCG, which stands for (−)-epigallocatechin-3-gallate, and ferulic acid are two dietary compounds with therapeutic potential, known as nutraceuticals. Prior studies have suggested that EGCG — which primarily comes from green tea leaves — may improve cognition and reduce inflammation. In mice, this compound has been shown to cross the blood-brain barrier and reduce the levels of amyloid beta — the main component of senile plaques.
The blood-brain barrier is a semipermeable membrane that protects the brain against the external environment, and is a major barrier for the efficient delivery of certain therapeutics that need to reach the brain and central nervous system.
Ferulic acid, found in carrots, tomatoes, rice, wheat, and pineapples, has both anti-inflammatory and antioxidant properties. In the context of Alzheimer’s, ferulic acid has been shown to block the generation of amyloid beta from its precursor, reversed cognitive deficits, and alleviated disease-related alterations in a mouse model.
Researchers from the University of Southern California (USC) and collaborators in Japan used a mouse model of Alzheimer’s disease to test if combining EGCG and ferulic acid would reduce learning and memory impairments, as well as amyloid beta formation and accumulation in the brain.
Each compound was given orally, either separately or in combination, once daily for three months to adult mice. The dose of both EGCG and ferulic acid was 30 milligrams per kilogram of body weight, which is well-tolerated by humans and common in a healthy diet, according to the scientists.
Results revealed that the combined treatment reversed cognitive impairment in tests of learning and memory. One of these tests was the Y-maze, an assessment of spatial memory, in which healthy mice typically prefer to explore a new arm of the maze rather than returning to one previously visited. Brain areas critical in memory and learning, such as the hippocampus and the prefrontal cortex, are involved in this task.
“After three months, combination treatment completely restored spatial working memory and the Alzheimer’s mice performed just as well as the healthy comparison mice,” Terrence Town, PhD, the study’s senior author from USC, said in a university news story, written by Leigh Hopper.
Additional behavioral and cognitive tests, which also showed benefits of combining EGCG and ferulic acid, assessed novel object recognition and the animals’ exploratory activity.
Data further showed that combining EGCG and ferulic acid lessened the buildup of amyloid beta in three specific brain areas (including the hippocampus) compared with either compound alone. The combo approach further increased the amount of a soluble form of amyloid beta precursor (APP) known to be associated with lower levels of amyloid beta and reduced that of a different version of APP that contributes to the accumulation of this key protein in Alzheimer’s.
Mice that were given EGCG and ferulic also showed decreased generation of beta-secretase, one of two enzymes involved in converting APP into smaller amyloid beta peptides that may aggregate in plaques.
Other benefits included less neuroinflammation, reduced levels of oxidative stress markers, and greater density of synapses, the sites where nerve cells communicate. Neuroinflammation was assessed via the activity of two cells types called astrocytes and microglia and also by the amount of pro-inflammatory molecules.
“Our findings offer preclinical evidence that combined treatment with EGCG and [ferulic acid] is a promising [Alzheimer’s] therapeutic approach,” the investigators wrote.
These findings of the potential benefits of dietary compounds for Alzheimer’s are “encouraging,” because rather than having “to wait 10 to 12 years for a designer drug to make it to market; you can make these dietary changes today,” said Town, who is a professor of physiology and neuroscience at the Keck School of Medicine of USC’s Zilkha Neurogenetic Institute.
He further said that his team will continue exploring combination approaches focusing on plant-derived substances that prevent the production of senile plaques.
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