Abstract
The current work represents a comparative study of the phenolic profiles of three under-explored Onosma (Boraginaceae) species from Greece-Onosma leptantha (OL), Onosma erecta (OE), and Onosma graeca (OG). Although Onosma spp. have ethnopharmacological significance, previous phytochemical studies have focused primarily on roots. Methanolic extracts of the aerial parts were analyzed using qualitative LC-MS enhanced by molecular networking-based dereplication, annotating 94 phenolics categorized into hydroxybenzoic acids (7), hydroxycinnamic acids (24), lignans (14), neolignans (14), stilbenes (4), coumarins (5), and flavonoids (26). OG exhibited the broadest distribution of flavonoid glycosides. OL contained the greatest number of hydroxycinnamic and neolignan derivatives, and OE was notably abundant in lignans. Total phenolic (TPC) and total flavonoid (TFC) contents were quantified, and the antioxidant capacity and enzyme inhibition against cholinesterases, α-amylase, and α-glucosidase were assessed. OL showed a high TPC (69.03 mg GAE/g extract) and strong antioxidant activity, while OG exhibited a high TFC (45.80 mg RE/g extract). All extracts demonstrated stronger AChE inhibition than BChE, with OG showing the highest AChE inhibition (2.35 mg GALAE/g). Additionally, OL was the most active against both α-glucosidase (5.69 mmol ACAE/g) and α-amylase (0.48 mmol ACAE/g). This study improved our understanding of the chemical diversity within these species, providing a more comprehensive insight into their longstanding ethnopharmacological potential.