Fossati_2026_Sci.Rep__

Neurodegenerative diseases represent a growing global health burden. With current treatments limited to symptom management, natural biodiversity offers a promising source of novel, multi-target compounds. Bioprospecting thus emerges as a sustainable strategy for discovering innovative neuroprotective therapies, underscoring the importance of preventing biodiversity for future drug discovery. An initial metabolomic screening of Italian plants was performed to support a bioprospective approach, in which 27 plant extracts were evaluated for their ability to inhibit acetylcholinesterase and tyrosinase, targeting mechanisms involved in neurodegenerative diseases. Adenophora liliifolia and Carissa macrocarpa emerged as the most promising species through multi-parameter screening. Metabolomic analysis showed that most identified metabolites exhibit activity against acetylcholinesterase and/or tyrosinase, supporting observed bioactivities. These extracts represent potential candidates for developing therapies against neurodegenerative diseases. These findings highlight systematic bioprospecting as a powerful strategy for identifying novel candidates with neuroprotective activity. By integrating traditional knowledge with modern metabolomic and biochemical approaches, this study demonstrates how underexplored plant biodiversity, such as Adenophora liliifolia and Carissa macrocarpa, can yield promising therapeutic candidates for targeting the complex multi-target mechanisms underlying neurodegenerative disorders.