Sterubin, an active chemical compound extracted from a native California plant, was found to hold neuroprotective and anti-inflammatory potential for Alzheimer’s disease, a study shows.
The study, “Old age-associated phenotypic screening for Alzheimer’s disease drug candidates identifies sterubin as a potent neuroprotective compound from Yerba santa,” was published in the journal Redox Biology.
Many therapeutic agents used to treat several diseases are based on chemical compounds found in nature, which have been used for centuries in traditional medicine.
With this in mind, researchers from the Salk Institute for Biological Studies in California decided to explore the potential of 400 different plant extracts to target known mechanisms involved in Alzheimer’s disease.
To evaluate the potential of the extracts, the team used a cell-based assay that enabled the identification of those that could specifically prevent a type of nerve cell death called oxytosis.
Oxytosis is a form of regulated cell death that is triggered by reduced levels of the antioxidant molecule glutathione, impaired transport of the nerve cell activator glutamate, and increased production of damaging oxygen reactive elements. This process has been described as relevant in age-related neurodegeneration, as well as in human diseases affecting the central nervous system.
Using this simple screening strategy, the researchers identified nine herbal extracts that were able to significantly protect cells from oxytosis. Upon further experiments, the researchers were able to reduce this list to two extracts of potential interest. Besides the neuroprotective activity, these two herbs also demonstrated anti-inflammatory activity and were able to support the maturation and growth of cells.
The team decided to focus their studies on one of these extracts derived from a shrub naturally found in California called Eriodictyon californicum, commonly known as Yerba santa.
“Yerba santa has long been known to have medicinal properties,” the researchers wrote. “Historically, it was used to treat a variety of indications including various respiratory conditions and fever as well as bruises, infections, and pain including headaches. Thus, its anti-inflammatory properties are well documented.”
A detailed examination of the different chemical compounds of Yerba santa extract revealed that one in particular, sterubin, was responsible for the neuroprotective effects observed in the cell-based assays.
Sterubin was found to be approximately four times more potent in preventing neurodegeneration than fisetin, a natural compound extracted from strawberries under evaluation as a therapy for Alzheimer’s disease.
“Not only did sterubin turn out to be much more active than the other flavonoids in Yerba santa in our assays, it appears as good as, if not better than, other flavonoids [a class of chemical compounds] we have studied,” Pamela Maher, PhD, staff scientist at Salk Institute and senior author of the study, said in a press release.
Treatment with purified sterubin was able to sustain glutathione levels and consequently prevent increased production of reactive oxygen species (ROS) in nerve cells. ROS are harmful to cells and are responsible for a phenomenon called oxidative stress, which is associated with a number of diseases.
This compound may also support cell survival by preventing ferroptosis, another cell death process triggered by iron accumulation that is closely linked to oxytosis.
Sterubin promoted the production of Nrf2 and ATF4, two important regulators of nerve cell metabolism and function, in a dose-dependent manner. In particular, treatment with sterubin increased the levels of p62 and HO-1, two proteins involved in protecting against oxidative stress and known to be regulated by Nrf2.
Genetic inhibition of Nrf2 or ATF4 followed by treatment with sterubin revealed that the therapeutic activity of this natural compound was most likely mediated by the regulation of Nrf2 and its downstream pathways rather than ATF4.
“Based on its potent Nrf2-inducing as well as neurotrophic, anti-inflammatory, and iron chelating properties, we believe that sterubin deserves further examination in the context of Alzheimer’s disease, as well as other neurodegenerative diseases,” the researchers wrote.
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