Neuroprotective Properties of the Coffee Component EHT

Abstract

Coffee is a complex mixture of more than eight hundred compounds with a variety of health benefits including reducing the risk of neurodegenerative diseases such as Alzheimer's and Parkinson's disease. A coffee compound, unrelated to caffeine, called eicosanoyl‐5‐hydroxytryptamide (EHT) has been identified as a regulator of the major serine/threonine phosphatase in the brain, protein phosphatase 2A (PP2A). In diseased tissue, PP2A exhibits reduced activity and methylation of its carboxy‐terminal tail. Previous reports indicate EHT is able to protect PP2A's methylation state and activity in vitro in addition to improving cognitive and motor function in animal models. In order to further understand the role of EHT in neuroprotection we sought to evaluate its ability to combat oxidative injury, structural damage and chemical toxicity in neuronal cell cultures. Utilizing lipid peroxidation as a marker for oxidative injury, we directly measured the formation of lipid hydroperoxides in the presence and absence of EHT. This colorimetric assay reports on the redox reaction between iron and hydroperoxides. Our results indicate that EHT is able to significantly reduce the production of the ferric ion suggesting EHT possesses antioxidant activity that may aid in maintaining membrane integrity. Next we studied the potential of EHT to reinforce the structural integrity of neurons, specifically analyzing their neuronal processes. Differentiated SH‐SY5Y neuroblastoma cells were treated with lysophosphatidic acid (LPA) to induce neurite retraction. Upon treatment with EHT, an increase in neurite length was observed suggesting protection from LPA. Lastly, the neuroprotection of SH‐SY5Y neuroblastoma cells against the chemical neurotoxin MPTP was evaluated. Dose‐dependent treatments with EHT resulted in maximal neuroprotection at a concentration of 100 nM. These data further support EHT as a component from coffee with neuroprotective activity.