Abstract
The study focuses on ultrasonication-assisted green solvent extraction of apigenin-7-o-glucoside from whole tomatoes (Solanum lycopersicum) and subsequent formulation of a novel hydrogel for epidermal wound healing. Optimisation of extraction parameters was performed using Box-Behnken design of experiments and predictive modelling by response surface methodology (RSM) as well as artificial neural network (ANN). HPTLC analysis confirmed a yield of 12.08 µg of apigenin-7-o-glucoside/g tomatoes (dwb) in the extract under the optimised extraction conditions (ethanol:water 1:1 ratio, 60 min, 55 °C). The presence of the same in highest abundance was validated by ESI-TOF-MS analysis of the extract. The ANN-based multilayer perceptron model (3-8-1 architecture) exhibited superior predictive accuracy (R (2) = 0.99 vis-à-vis 0.86), outperforming RSM, with extraction temperature being the most influential factor. The Extract(Best) was truly unique in exhibiting significant antimicrobial activity with low minimum inhibitory concentrations across a broad microbial spectrum, namely, ATCC strains of Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and methicillin-resistant Staphylococcus aureus. The extract was incorporated into a synthetic hydrogel, which displayed uniform morphology, a particle size of 100.99 ± 10.22 nm nm, and notable antimicrobial efficacy. In vitro release profile revealed first-order release kinetics (69% burst release) of the extract-loaded hydrogel. This is reportedly the first shelf-stable hydrogel utilising a novel apigenin-7-o-glucoside-rich green extract of tomatoes with strong antibacterial and antifungal activities and effective wound healing properties, as demonstrated in rabbit models. Human panellists favoured its cosmetic attributes such as colour, odour, spreadability, non-stickiness, and shine, suggesting its potential as a moisturising therapeutic gel safe for human use. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-025-04489-x.