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The medicinal powers of aspirin, digitalis and artemisinin antimalarial are all of plant origin. The Salk Institute's discovery of a potent neuroprotective and anti-inflammatory chemical substance in a California shrub could lead to a treatment for Alzheimer's disease based on a natural compound. The research appears in the February 2019 issue of the journal Redox biology.
"Alzheimer's disease is one of the leading causes of death in the United States," said Pamela Maher, a senior scientist, a member of Salk's Cellular Neurobiology Laboratory, led by Professor David Schubert. "And as age is a major risk factor, researchers are studying ways to counter the effects of aging on the brain.Our identification of sterubine as a potent neuroprotective component of a plant native to California called Yerba santa (Eriodictyon californicum) is a promising step in this direction ".
The native tribes of California, who nicknamed the plant "sacred grass" in Spanish, have long used the yerba santa for its medicinal properties. Devotees infuse her leaves to treat respiratory affections, fever and headaches; and crush it in a poultice for wounds, muscular pains and rheumatism.
To identify natural compounds that could reverse the symptoms of a neurological disease, Maher applied a screening technique used in drug discovery to a commercial library of 400 plant extracts with known pharmacological properties. The laboratory had previously used this approach to identify other chemicals (called flavonoids) from plants with anti-inflammatory and neuroprotective properties.
Through screening, the laboratory identified a molecule called sterubine as the most active component of Yerba santa. The researchers tested the impact of sterubin and other plant extracts on energy depletion in mouse nerve cells, as well as on other neurotoxicity and survival pathways associated with age, directly related to reduced energy metabolism, accumulation of misfolded aggregated proteins and inflammation observed in Alzheimer's disease. Sterubin has had a powerful anti-inflammatory effect on brain cells called microglia. It was also an effective iron remover – potentially beneficial because iron can help damage nerve cells during aging and neurodegenerative diseases. Overall, the compound was effective against several inducers of cell death in nerve cells, according to Maher.
"It's a compound that was known but ignored," says Maher. "Not only did Sterubin prove to be much more active than the other Yerba Santa flavonoids in our analyzes, but it seems to be as good, if not better, than the other flavonoids we have studied."
The laboratory then plans to test the sterubine in an animal model of Alzheimer's disease and then determine its drug characteristics and its level of toxicity in animals. With these data, says Maher, it might be possible to test the compound in humans, although it is essential to use sterubin derived from plants grown under standardized and controlled conditions. She says the team will probably generate synthetic derivatives of the sterubine.
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Material provided by Salk Institute. Note: Content can be changed for style and length.
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