The citrus industry produces large amounts of waste rich in bioactive compounds that have important effects on human health. Their extraction was performed using organic solvents, and a greener alternative to those solvents are natural deep eutectic solvents (NADES). The present study aimed to obtain and optimize extracts rich in polyphenols and flavonoids from orange peels using NADES and monitor polyphenol stability in the extracts for 30 days. The software COSMOtherm (conductor-like screening model) was used to screen fourteen NADES. The most promising solvents were lactic acid:glucose (LA:Glu) with an extraction yield of 1932 ± 7.83 mgGAE/100 gdw for TPC (total polyphenol content) and 82.7 ± 3.0 mg/100 gdw for TFC (total flavonoid content) and in the case of L-proline:malic acid (LP:MA) was 2164 ± 5.17 mgGAE/100 gdw for TPC and 97.0 ± 1.65 mg/100 gdw for TFC. The extraction process using LA:Glu and LP:MA was optimized, and the results showed that the selected variables (%NADES, solid:liquid ratio, and extraction time) had a significant influence on the extraction of TPC and TFC. Results showed that NADES improve the stability of TPC. These findings revealed that NADES are efficient for the extraction of bioactive compounds from orange by-products, and these extracts can represent an alternative for the food industry to enrich food products with natural ingredients.

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