Old age-associated phenotypic screening for Alzheimer's disease drug candidates identifies sterubin as a potent neuroprotective compound from Yerba santa
0301 basic medicine
Medicine (General)
QH301-705.5
Plant Extracts
Drug Evaluation, Preclinical
Reproducibility of Results
PC12 Cells
Eriodictyon
Mass Spectrometry
Neuroprotection
Rats
3. Good health
Mice
03 medical and health sciences
R5-920
Neuroprotective Agents
Phenotype
Animals
Humans
Biology (General)
Reactive Oxygen Species
Chromatography, High Pressure Liquid
Research Paper
DOI:
10.1016/j.redox.2018.101089
Publication Date:
2018-12-20T21:34:19Z
AUTHORS (5)
ABSTRACT
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.
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