Effects of Polyphenolic Extracts from Mediterranean Forage Crops on Cholinesterases and Amyloid Aggregation Relevant to Neurodegenerative Diseases

Alzheimer’s and Parkinson’s diseases are the most common neurodegenerative disorders of the central nervous system, characterized by progressive neuronal death and neurological dysfunction. There is currently no treatment that effectively slows the disease progression, and the synthetic drugs proposed to alleviate the symptoms, often cause side effects. Many studies are now focused on neuroprotective properties exhibited by natural agents, such as polyphenols, whose action on different cell signaling pathways is well known. In this article, we analyzed the composition and the properties of polyphenolic extracts from forage plants, such as Lotus ornitopoidioides , Hedysarum coronarium L. , Medicago sativa and Cichorium intybus . The LC-MS/MS analysis on the extracts allowed the identification of total 24 phenolic acids and 25 flavonoids. The effects of the extracts on key enzymes of cholinergic neurotransmission, such as acetyl cholinesterase and butyryl cholinesterase, was examined, together with an investigation on the aggregation and disaggregation of amyloid fibrils. The polyphenols acted as inhibitors of the considered enzymes, and interfered with the amyloidogenesis process, with differences depending on the specific extracts. The inhibition constants towards cholinesterases ranged in the 60 – 240 µM interval; the extracts showed different inhibition mechanisms, from competitive to non-competitive. Differences also emerged in the amyloidogenesis process, with IC ₅₀ values comprised in a large interval. Finally, the extract from M. sativa significantly reduced the cell viability of the human neuroblastoma cell line SH-SY5Y. These results suggest that polyphenols extracted from these plants may behave as multitargeting agents against key factors of Alzheimer’s and Parkinson’s diseases. Therefore, they can be considered as promising candidates for the prevention and management of symptoms of these neurodegenerative disorders in combination with pharmacological therapies.