Metabolic Profiling via UPLC/MS/MS and In Vitro Cholinesterase, Amylase, Glucosidase, and Tyrosinase Inhibitory Effects of Carica papaya L. Extracts Reveal Promising Nutraceutical Potential

Carica papaya (Family Caricaceae) is endowed with a myriad of biological activities as gastroprotective, antidiabetic, antimalarial, antiviral, and anti-inflammatory agent. We performed for the first time an extensive comparative metabolite profiling of different plant organs considering both male and female leaves, seeds, and fruits of different maturity stages. The phytochemical fingerprinting-via UPLC/MS/MS- of C. papaya led to tentative identification of 84 metabolites belonging to different primary and secondary phytoconstituents to include alkaloids (carpaine derivatives), flavonoids, glucosinolates, organic and phenolic acids, amino acids, and carbohydrates. The seeds’ profile was enriched with hydroxybenzoic acids and their derivatives, while leaves were characterized by the prevalence of carpaine alkaloids, flavonoids, lipids, and alkylated sugars. Correlation analysis revealed a significant positive correlation between total phenolic content and the antioxidant assays (ferric reducing antioxidant property (FRAP), 2, 2-diphenyl-1- picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), cupric-reducing antioxidant capacity (CUPRAC), and total antioxidant capacity (TAC)). Principal component analysis was applied to find out possible phytochemical trends across C. papaya matrices, where PC1 and PC2 accounted for 46.57 and 19.93% of the variability in the data set with well-separated extracts into groups mostly on the basis of plant organ. The PCA model showed that immature seeds had the highest antioxidant properties, while leaves separated from fruit and mature seeds due to higher butyrylcholinesterase and α-amylase inhibition, but lower acetylcholinesterase and α-glucosidase inhibition activity. We corroborate the better exploitation of both edible and inedible parts of C. Papaya in nutraceutical supplements after sufficient in vivo and toxicity studies.