It would seem that Juan Ponce de Leon’s trip to the New World in search of the fountain of youth may have been even more in vain, given that it may have been right in his “backyard.” Evidence from a new study by investigators at the University of Malta and the Centre National de la Recherche Scientifique (CNRS/University of Bordeaux) shows that chemicals in ubiquitous Mediterranean plants could hold the key to delaying age-related diseases.
Chemicals extracted from the prickly pear and brown seaweed—two pervasive Mediterranean plants—have been elevated to possible drug candidates to combat neurodegenerative diseases, such as Alzheimer’s (AD) and Parkinson’s (PD). These age-related disorders are characterized by the accumulation of sticky protein clumps that over time damage the nervous system to erode mobility or memory.
“We have long been screening plants scattered across the Mediterranean for small molecules that interfere with the buildup of toxic protein aggregates,” explained co-senior study investigator Neville Vassallo, M.D., Ph.D., professor of molecular physiology at the University of Malta School of Medicine and Surgery. “The robust effects of chemicals derived from the prickly pear and brown seaweed confirm that our search has certainly not been in vain.”
The researchers began by screening plant extracts with genetically engineered yeast strains that were designed to overproduce beta-amyloid clumps, a hallmark of AD. Following exposure to the chemicals, the yeast's health improved dramatically, a result that encouraged the researchers to evaluate the molecules on fruit flies that had been genetically modified to develop Alzheimer's symptoms.
The findings from this study were published recently in Neuroscience Letters in an article entitled “Extracts from Two Ubiquitous Mediterranean Plants Ameliorate Cellular and Animal Models of Neurodegenerative Proteinopathies.” “We investigated whether extracts derived from two ubiquitous Mediterranean plants namely, the prickly pear Opuntia ficus-indica (EOFI) and the brown alga Padina pavonica (EPP) alleviated neurodegenerative phenotypes in yeast (Saccharomyces cerevisiae) and fly (Drosophila melanogaster) models of AD and PD,” the authors wrote. “Pre-treatment with EPP or EOFI in the culture medium significantly improved the viability of yeast expressing the Arctic Aβ42 (E22G) mutant. Supplementing food with EOFI or EPP dramatically ameliorated lifespan and behavioural signs of flies with brain-specific expression of wild-type Aβ42 (model of late-onset AD) or the Arctic Aβ42 variant (model of early-onset AD). Additionally, we show that either extract prolonged the survival of a PD fly model based on transgenic expression of the human α-syn [α-synuclein] A53T mutant.”
Interestingly, regular treatment with seaweed extract extended the median lifespan of diseased flies by 2 days. A greater 4-day extension was observed when prickly pear extract was administered. At first glance this may seem small; howeve, considering that 1 day in the life of a fruit fly is roughly equivalent to around 1 year in humans, the results are dramatic.
The investigators also discovered that the extracted substances prolonged the lifespan of flies with brains overloaded with α-synuclein, a gummy protein associated with PD—underscoring an effect on neurodegenerative mechanisms shared by both AD and PD. The research team found that the plant-derived molecules interfered with the build-up of both beta-amyloid and α-synuclein proteins' ability to generate clumps, which ultimately makes them toxic to neurons.
“We believe that the discovery of bioactive agents that target pathways that are hit by multiple neurodegenerative conditions is the most viable approach in our current fight against brain disorders,” remarked co-senior study investigator Ruben Cauchi, Ph.D., senior lecturer at the Centre for Molecular Medicine and Biobanking within the University of Malta. “A clear advantage of the drugs used in this study is that, in view of their excellent safety profile, they are already on the market as nutraceuticals and cosmeceuticals.”
The researchers are currently working with the Institute of Cellular Pharmacology—the company that extracts the neurodegenerative disease-fighting compounds—to formulate compounds for clinical trial use. If future findings are in line with the current study, then the Mediterranean may quickly become more than a haven for lovers of crystal-clear seas and sun-kissed landscapes.