The rosmarinic acid (RA) is known as the major phenolic compound in comfrey roots possessing notable biological properties. This study aimed to enhance the polyphenol content of the comfrey root extract through the use of six different types of macroporous resins chromatography including DM-130, LXA-88, LSD-001, LXA-10, HP-20, and LXA-17. The LSD-001 demonstrated the highest separation efficiency, resulting in a 7-fold increase of RA content from 11.44 mg.g−1 in the extract to 75.79 mg.g−1 for the desorbed extract, as confirmed by HPLC analysis. In optimization of the static adsorption, 40 min contanct time, 11.8 g resin dosage, and 10000 µg mL−1 extract concentration were attained for maximum amount of adsorption capacity and ratio. Also in desorption process the minmum time for maximum recovery was 7 min with 60 mL eluent volume. The isotherm and kinetic studies of RA adsorption on LSD-001 resin showed reasonable agreement with Langmuir suggesting monolayer adsorption machenism, and the pseudo-second-order models (R2=0.98). Morover, the enriched extract containg the highest amount of RA showed an antioxidant activity of almost 3.5 times more than the comfrey root extract. Molecular modeling revealed stacking interactions and hydrogen bonding between the polar sites of RA and the benzene ring of LSD-001 resin. Furthermore, molecular docking of the ligand with the polymer yielded a docking score of −5.75 kcal.mol−1 revealed the incorporation of RA and polymeric structure of LSD-001 ion exchange resin.
