In 2015, Youyou Tu won the Nobel Prize in Physiology or Medicine for her work and discovery of artemisinin—a compound derived from the sweet wormwood plant—as a treatment for malaria. Tu’s work underscored not only the immense value of natural products in fighting disease but also the importance of evaluating traditional folk remedies during the drug discovery process. In that vein, investigators at the Salk Institute have new evidence of a potent neuroprotective and anti-inflammatory chemical found in a native California shrub, which may lead to a treatment for Alzheimer’s disease.

Yerba santa (Eriodictyon californicum), which native California tribes dubbed the “holy herb” for its medicinal properties lies at the center of this new research. Folk remedies described how people would brew the plant’s leaves to treat respiratory ailments, fever, and headaches, as well as mash it into a poultice for wounds, sore muscles, and rheumatism. In this new study, the Salk team applied a screening technique used in drug discovery to a commercial library of 400 plant extracts with known pharmacological properties. The lab had previously used this approach to identify other chemicals (called flavonoids) from plants that have anti-inflammatory and neuroprotective properties.

Findings from the study were published recently in Redox Biology through an article titled “Old age-associated phenotypic screening for Alzheimer’s disease drug candidates identifies sterubin as a potent neuroprotective compound from Yerba santa.”

W.Fischer, et al., Redox Biology 21 (2019) 101089

Through the screen, the lab identified a molecule called sterubin as Yerba santa’s most active component. The researchers tested sterubin and other plant extracts for their impact on energy depletion in mouse nerve cells, as well as other age-associated neurotoxicity and survival pathways directly related to the reduced energy metabolism, accumulation of misfolded, aggregated proteins, and inflammation seen in Alzheimer’s. Sterubin had a potent anti-inflammatory impact on brain cells known as microglia. It was also an effective iron remover—potentially beneficial because iron can contribute to nerve cell damage in aging and neurodegenerative diseases. Overall, the compound was effective against multiple inducers of cell death in the nerve cells.

“Alzheimer’s disease is a leading cause of death in the United States,” explained senior study investigator Pamela Maher, PhD, a member of Salk’s Cellular Neurobiology Laboratory. “And because age is a major risk factor, researchers are looking at ways to counter aging’s effects on the brain. Our identification of sterubin as a potent neuroprotective component of a native California plant called Yerba santa is a promising step in that direction.”

The Salk team plans to test sterubin in an animal model of Alzheimer’s, then determine its drug-like characteristics and toxicity levels in animals. With that data, Maher says, it might be possible to test the compound in humans, although it would be critical to use sterubin derived from plants grown under standardized, controlled conditions. She says the team will likely generate synthetic derivatives of sterubin.

“This is a compound that was known but ignored,” Maher concluded. “Not only did sterubin turn out to be much more active than the other flavonoids in Yerba santa in our assays, but it also appears as good as, if not better than, other flavonoids we have studied.”

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