Unlocking Matricaria chamomilla bioactives: Process optimization via betaine-NADES extraction, metabolic profiling, and antityrosinase activity

This work investigates the use of betaine-based natural deep eutectic solvents (NADES) integrated with ultrasound-assisted extraction (UAE) to extract bioactive compounds from chamomile (Matricaria chamomilla L.). It focuses on optimizing phenolic and flavonoid extraction and evaluates their antityrosinase activity. Nine betaine-based NADES were prepared and tested for total phenolic (TPC) and total flavonoid (TFC) content, and compared with traditional ethanolic (EtOHmac) and UAE ethanolic (EtOHUS) extracts. Antioxidant activity was measured using DPPH, ABTS, and FRAP assays. The highest TPC and TFC were obtained for the NADES composed of betaine-1,3-propanediol 1:2 (N5). The optimization of N5 (N5opt) was carried out using a Box-Behnken design (BBD) to determine the effects of the plant-to-NADES ratio, extraction temperature, extraction time, and water percentage. The Response Surface Methodology (RSM) defined the optimized plant-to-solvent ratio, temperature, time, and water percentage, resulting in increases of 42% and 17% in TPC and TFC, respectively. Due to the relevance of polyphenols as tyrosinase inhibitors, the antityrosinase activity of the traditional, N5, and N5opt extracts was evaluated. No significant differences were found among the N5, N5opt, and EtOHUS extracts, whereas the EtOHmac extract showed markedly lower activity. The metabolomic characterization of the N5opt was completed by using Ultra-High Performance Liquid Chromatography - High Resolution Mass Spectrometry (UHPLC–HRMS). The results showed the prevalence of phenolic and flavonoid compounds. These findings showed that M. chamomilla N5opt extract exhibits good antioxidant activity and acts as a tyrosinase inhibitor, suggesting it could be used as a depigmenting agent for skin disorders.