Optimization of the Chitosan-Assisted Extraction for Phillyrin and Forsythoside A from Forsythia suspensa Leaves Using Response Surface Methodology

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Abstract
In this study, a green and efficient extraction methodology was developed by leveraging the unique properties of chitosan—namely its non-toxicity, biocompatibility, and adhesive nature—to enhance the recovery of bioactive ingredients from Forsythia suspensa leaves. The core mechanism involves the formation of complexes between chitosan and the target bioactive ingredients, which significantly boosts their extraction efficiency. To substantiate this mechanism, comprehensive characterization was performed using Powder X-ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), and molecular docking analyses. The results provided robust evidence of a strong interaction between chitosan and the bioactive ingredients, leading to a marked enhancement in both the stability and aqueous solubility of the target compounds. For process optimization, a multi-objective approach was implemented using the Non-dominated Sorting Genetic Algorithm II (NSGA-II) to simultaneously maximize the extraction yields of phillyrin and forsythoside A. The algorithm identified the optimal parameters as a leaf-to-chitosan mass ratio of 10:11.75, a solid-to-liquid ratio of 1:52 g/mL, a temperature of 80 °C, and a duration of 120 min. Under these optimized conditions, the corresponding extraction yields for phillyrin and forsythoside A were 1.68 ± 0.16% and 3.23 ± 0.27%, respectively. These findings collectively indicate that chitosan-assisted extraction represents a highly promising and advanced technology for the sustainable and effective extraction of bioactive ingredients from botanical sources.

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