Assessment of inhibitory properties of flavonoid-rich fig (Ficus carica L.) peel extracts against tyrosinase, α-glucosidase, urease and cholinesterases enzymes, and relationship with antioxidant activity

Introduction: Key-enzyme inhibition is a recent approach for the treatment of some health disorders, including diabetes, skin hyperpigmentation, Alzheimer's disease, and some microbial infections. Looking for potential natural multi-target inhibitors, flavonoid-rich extracts from the peel of Ficus carica fruits were simultaneously tested against five enzymes and various methods were used to evaluate their antioxidant activity. Methods: Extracts from peels from F. carica cultivars (Bakor Noir, Bouankik, Azenjer, and Tazegaght) were prepared using methanol acidified by 5% citric acid. Inhibitory activities of extracts at 10 mg/mL were measured in vitro against alpha-glucosidase, tyrosinase, urease, acetylcholinesterase, and butyrylcholinesterase. Also, the antioxidant activity was evaluated using free radical scavenging, iron and copper chelating, and reducing assays. Results: Extracts were efficient in inhibiting tyrosinase and alpha-glucosidase (IC50 values from 0.09 to 0.45, and 1.18 to 3.38 mg/mL, respectively). However, a weak inhibition was observed against urease and cholinesterases. Among the antioxidant activities studied, extracts were more efficient for copper chelation and radical scavenging (IC50 values from 0.05 to 0.13, and 0.30 to 1.33 mg/mL, respectively). Phytochemical analysis revealed the extraction of large quantities of flavonoids (up to 50.4 mg/g of peels), mainly flavonols (up to 81% of total flavonoids). Given the specific extract composition, including two fractions (flavonoids and citric acid), a strong synergy was observed for enzyme inhibition and metal chelation. Conclusion: Flavonoid-rich extracts from F. carica could be considered as multifunctional bioactive ingredients to be used in anti-hyperglycemic and skin-whitening pharmaceutical formulations.