Green and efficient approach to extract bioactive flavonoids with antioxidant, antibacterial, antiglycation, and enzyme inhibitory activities from navel orange peel

Numerous previous studies have reported the extraction of flavonoids from orange peels, but a green and efficient approach suitable for the large-scale industrial production of flavonoids with versatile and excellent biological activities is still lacking. To tackle this issue, two easily accessible extraction methods, namely heat reflux (HR) and ultrasonication (US), coupled with four solvents (95% ethanol, 70% aqueous ethanol solution, methanol, and ethyl acetate), were used in the present study to extract flavonoids from navel orange peel, followed by chemical profile and biological activity (antioxidant, antibacterial, antiglycation, and enzyme inhibition) evaluation of all extracts obtained. The highest total phenolic content (TPC, 336.56 μmol GAE/g), total flavonoid content (TFC, 1194.31 μmol QE/g), flavonoid glycosides content (FGs, 461.82 mg/g), and the best antioxidant (IC50 = 21.35 mg/L for ABTS assay) and α-glucosidase inhibition (IC50 = 49.38 mg/L) activities, were found in the extract obtained by HR using ethyl acetate (EtOAc HR). However, the extract obtained by US with ethyl acetate (EtOAc US) contained the highest content of polymethoxyflavones (PMFs, 152.07 mg/g), and showed the most potent antiglycation (IC50 = 71.26 mg/L), antibacterial (MIC = 0.078 mg/mL against MRSA), and acetylcholinesterase inhibition (AChE, IC50 = 179.19 mg/L) activities compared to the other extracts. Furthermore, Pearson's correlation analysis was performed. This study provides simple and cost-effective methods for the preparation of orange peel extracts rich in flavonoids and versatile in biological activities, which will greatly contribute to the valorization of orange peel in food, pharmaceutical, and cosmetic industries.