Carob (Ceratonia siliqua) leaves: A comprehensive analysis of bioactive profile and health-promoting potential of an untapped resource.

Carob is a resilient plant with ecological and nutritional significance. A comprehensive study of Ceratonia siliqua leaves (CSL) was conducted to explore its chemical composition and health-promoting potential, aiming at improving the carob-crop sustainability through valorization of this untapped co-product. UHPLC-DAD-HRMS/MS quali-quantitative profiling of CSL revealed high levels of n-galloylated glucoses (129-196 mg g) and flavonol-glycosides (36-42 mg g), with siliquapyranone (39-56 mg g), 1,2,3,6-tetragalloylglusose (47-69 mg g) and myricitrin (27-33 mg g) as main markers. Highest bioactive content and antioxidant capacity (5.0 and 3.1 TEAC) was obtained during pods harvesting. Besides significant antioxidant potential, CSL exhibited strong-high inhibitory activity against α-glucosidase, acetylcholinesterase and butyrylcholinesterase (IC, 0.51, 13.5 and 58.0 μg mL, respectively). 1,2,3,6-tetragalloylglusose and siliquapyranone are the main contributors to antioxidant and α-glucosidase inhibitory capacities. Excellent ability of extract and 1,2,3,6-tetragalloylglusose (IC, 0.05 μM) in selectively inhibiting α-glucosidase, make them promising candidates to manage hyperglycemia with fewer side effects.