Ultrasound-Assisted Extraction and RSM Optimisation of Phenolic Compounds from Helichrysum arenarium with Chlorogenic Acid Quantification

Abstract Helichrysum arenarium L. Moench is a phenolic-rich plant, yet optimised extraction and characterisation of its bioactive compounds remain limited. This study developed an ultrasound-assisted extraction method combined with response surface methodology and central composite design to optimise the recovery of total phenolics, antioxidant activity, and chlorogenic acid. The effects of ethanol concentration, solvent-to-solid ratio, temperature, and time were evaluated. Under optimal conditions, total phenolic content reached 40.86 mg gallic acid equivalents/g dry weight, antioxidant activity showed 88.9% DPPH inhibition, and chlorogenic acid content was 2.02 mg/g dry weight. The models showed good agreement between predicted and experimental values. Chlorogenic acid was quantified using a validated HPLC–PDA method. Molecular docking suggested a stable interaction of chlorogenic acid with the CYP2C19 enzyme. The optimised approach offers an efficient strategy for extracting natural antioxidants from H. arenarium for use in food and nutraceutical applications.