Chemical in California Shrub Could Help Treat Alzheimer’s Disease

The Salk Institute discovered a potent neuroprotective and anti-inflammatory chemical in a native California shrub may lead to a treatment for Alzheimer’s disease based on a compound found in nature.

Alzheimer’s is the most common cause of dementia, a general term for memory loss and other cognitive abilities serious enough to interfere with daily life. Alzheimer’s disease causes 60 percent to 80 percent of dementia cases. An estimated 5.7 million Americans of all ages are living with Alzheimer’s dementia in 2018. It is estimated that there are approximately 44 million people worldwide living with Alzheimer’s disease or a related form of dementia.

Native California tribes, which dubbed the plant “holy herb” in Spanish, have long used Yerba santa for its medicinal properties. Devotees brew its leaves to treat respiratory ailments, fever and headaches; and mash it into a poultice for wounds, sore muscles and rheumatism.

To identify natural compounds that might reverse neurological disease symptoms, Maher 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.

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. The compound was effective against multiple inducers of cell death in the nerve cells, according to Maher.

Next, the lab 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.

Redox Biology – Old age-associated phenotypic screening for Alzheimer’s disease drug candidates identifies sterubin as a potent neuroprotective compound from Yerba santa

Abstract – Old age-associated phenotypic screening for Alzheimer’s disease drug candidates identifies sterubin as a potent neuroprotective compound from Yerba santa

Alzheimer’s disease (AD) is the most frequent age-associated dementia with no treatments that can prevent or slow its progression. Since age is by far the major risk factor for AD, there is a strong rationale for an alternative approach to drug discovery based upon the biology of aging. Phenotypic screening assays that reflect multiple, age-associated neurotoxicity pathways rather than single molecular targets can identify compounds that have therapeutic efficacy by targeting aspects of aging that contribute to AD pathology. And, while the suitability of any single assay can be questioned, a combination of assays can make reliable predictions about the neuroprotective effects of compounds in vivo. Therefore, our lab has developed a combination of phenotypic screening assays that are ideally suited not only to identify novel neuroprotective compounds for the treatment of AD but also their target pathways, thereby potentially providing new therapeutic targets for disease treatment. Using these assays, we screened a large library of extracts from plants with identified pharmacological uses. Analysis of one of these extracts from the plant Yerba santa (Eriodictyon californicum) identified the flavanone sterubin as the active component and further studies showed it to be a potent neuroprotective and anti-inflammatory compound.

Highlights

• Phenotypic screening of a curated library of plant extracts identifies Yerba santa.
• The flavonoid sterubin is the main active component of Yerba santa.
• Sterubin is very neuroprotective against multiple toxicities of the aging brain.
• Sterubin has potent anti-inflammatory activity that is dependent on Nrf2 induction.
• Sterubin is also an iron chelator which could enhance its neuroprotective activity.

SOURCES- Salk Institute, Redox Biology, Alzheimers Society

Written By Brian Wang. Nextbigfuture.com

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