Abstract

Helichrysum plicatum DC. is an important source of bioactive secondary metabolites with a variety of pharmacological activities. To obtain highly potent extracts with the maximum level of phenolic glycosides and total phenolic compounds, this study aimed to establish an eco-friendly cyclodextrin-assisted extraction procedure from H. plicatum flowers. Response surface methodology (RSM) and artificial neural networks (ANN) were used to optimize the ultrasound-assisted extraction (UAE) by evaluating sonication temperature, time, concentrations of ethanol and two types of cyclodextrins (β-CD and HP-β-CD). Comprehensive statistical validation revealed better predicting capacity of the created ANN models compared to the traditional RSM. The highest positive effects were observed for the ethanol concentration and the extraction temperature. Both types of CDs showed not only positive impact on the extraction efficiency of bioactives, but also on their stability after exposure to stress conditions. Molecular docking was used to additionally reveal interactions within the studied inclusion complexes. Conclusively, the HP-β-CD-assisted extraction conducted at 80 °C for 40 min, utilizing 62% ethanol and 1.60% HP-β-CD, was the most optimal due to its ability to minimize ethanol consumption while achieving maximal recovery of bioactives, in comparison to β-CD (80%). Under these optimized conditions, experimentally obtained results for isoquercitrin (0.50 mg/g DW), kaempferol-3-O-glucoside (5.83 mg/g DW), apigenin-7-O-glucoside (1.34 mg/g DW), and total polyphenolic (28.51 mg GAE/g DW) content were in agreement with the values predicted by ANN.

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