An innovative approach for the recovery of nobiletin, hesperidin, and other phytochemicals from tangerine leaves (Citrus reticulata) by-products using a solvent mixture based on natural compounds

Citrus reticulata leaves, rich in phytochemicals, are underutilized by-products with sustainable valorization potential under Green Chemistry principles. This study developed an eco-friendly solvent combining thymol (Thy), oxalic acid (OA), and ethanol (EtOH) to extract nobiletin and hesperidin guided by COSMO-RS and high-intensity ultrasound (HIUS). The optimum solvent composition (0.9 % oxalic acid, 24.1 % thymol and 75 % EtOH) achieved higher yields of nobiletin (0.38 mg mL−1), hesperidin (0.74 mg mL−1) than pure EtOH (0.30 mg mL−1 of nobiletin and 0.64 mg mL−1 of hesperidin). HPLC-DAD-MS/MS and GC–MS analyses revealed that the optimized extract had a more complex phytochemical profile with a richer composition than the EtOH extract. Furthermore, optimized Thy-OA-EtOH extract exhibited superior bioactivity, with enhanced antioxidant capacity and neuroprotective effects (IC50: 334.40 mg mL−1) compared to HIUS-EtOH (IC50: 1482.20 mg mL−1). This study highlights the potential of natural compound mixtures with HIUS for extracting phytochemicals from citrus leaves for food and pharmaceutical applications.

Authors acknowledge the funding from projects PID2020–113050RB-I00, and PDC2021–120814-I00 (MCIN/AEI/10.13039/501100011033 and The European Union Next GenerationEU/PRTR), and CSIC (INCGLO0019 - Bioprospection of local agricultural resources, a way to achieve the Objectives of Sustainable development). The authors are also thankfull for Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (88887.877048/2023-00, CAPES PRINT, Brazil), National Council for Scientific and Technological Development (CNPq, 150281/2024-2), and Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP (grant number: 2023/05722-6, 2023/12621-1, 2022/10469-5). We are also thankful to the Universidad Nacional de Colombia (Hermes 57909).

Peer reviewed