Metabolite Profiling of Microwave-Assisted Sargassum fusiforme Extracts with Improved Antioxidant Activity Using Hybrid Response Surface Methodology and Artificial Neural Networking-Genetic Algorithm

Sargassum fusiforme (SF) is a popular edible brown macroalga found in Korea, Japan, and China and is known for its health-promoting properties. In this study, we used two sophisticated models to obtain optimized conditions for high antioxidant activity and metabolite profiling using high-resolution mass spectrometry. A four-factor central composite design was used to optimize the microwave-assisted extraction and achieve the maximum antioxidant activities of DPPH (Y(1): 28.01 % inhibition), ABTS (Y(2): 36.07 % inhibition), TPC (Y(3): 43.65 mg GAE/g), and TFC (Y(4): 17.67 mg CAE/g), which were achieved under the optimized extraction conditions of X(1): 47.67 %, X(2): 2.96 min, X(3): 139.54 °C, and X(4): 600.00 W. Moreover, over 79 secondary metabolites were tentatively identified, of which 12 compounds were reported for the first time in SF, including five phenolic (isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate, 3,4-dihydroxyphenylglycol, scopoletin, caffeic acid 4-sulfate, and cinnamoyl glucose), two flavonoids (4’,7-dihydroxyisoflavone and naringenin), three phlorotannins (diphlorethohydroxycarmalol, dibenzodioxin-1,3,6,8-tetraol, and fucophlorethol), and two other compounds (dihydroxyphenylalanine and 5-hydroxybenzofuran-2(3H)-one) being identified for the first time in optimized SF extract. These compounds may also be involved in improving the antioxidant potential of the extract. Therefore, optimized models can provide better estimates and predictive capabilities that would assist in finding new bioactive compounds with improved biological activities that can be further applied at a commercial level.