Isolating Anti-Alzheimer’s Compounds From Traditional Medicine

Japanese scientists identified active compounds from a plant used in traditional medicine that can improve memory and reduce symptoms of Alzheimer's disease in mice. Their findings have been published in Frontiers in Pharmacology.

Plants typically contain a huge variety of compounds, only a small number of which have significant effects on the human body. If a plant medicine shows a therapeutic effect, scientists are interested in isolating and identifying the compounds that cause the effect to see if they can be used as new drugs.

In many cases, scientists repeatedly screen crude plant medicines in lab experiments to see if any compounds show a particular effect in cells grown in a dish or in cell-free assays. If a compound shows a positive effect in cells or test tubes, it could potentially be used as a drug, and the scientists go on to test it in animals.

However, this process is a lot of work and doesn't account for changes that can happen to drugs when they enter the body; enzymes in the blood and liver can metabolize drugs into various forms called metabolites.

“The candidate compounds identified in traditional benchtop drug screens of plant medicines are not always true active compounds, because these assays ignore bio-metabolism and tissue distribution,” explained study senior author Professor Chihiro Tohda of Toyama University. “So, we aimed to develop more efficient methods to identify authentic active compounds that take these factors into account.”

The scientists were interested in finding active compounds for Alzheimer's disease in Drynaria rhizomes, a traditional plant medicine. Initially, the researchers mashed the plant up and treated Alzheimer's model mice orally using this crude plant extract. They found that the plant treatment reduced memory impairments and levels of amyloid and tau proteins in their brains.

In a key step, the team then examined the mouse brain tissue five hours after they treated the mice with the extract. They found that three compounds from the plant had made it into the brain: a compound called naringenin and two naringenin metabolites.

The researchers then treated the mice with pure naringenin and noticed the same improvements in memory deficits and reductions in amyloid and tau proteins. They found a protein called CRMP2 that naringenin binds to in neurons and causes them to grow, suggesting that this could be the mechanism by which naringenin can improve Alzheimer's disease symptoms.

The team hope that the technique can be used to identify other treatments.

“We are applying this method to discover new drugs for other diseases such as spinal cord injury, depression and sarcopenia,” explained Tohda.

The article can be found at: Yang et al. (2017) A Systematic Strategy for Discovering a Therapeutic Drug for Alzheimer’s Disease and Its Target Molecule.