Abstract
In this study, an integrated, green chemical approach was developed for the highly efficient extraction of bioactive flavonoids from Sideritis scardica (Macedonian mountain tea) using tailor-made Choline Chloride-based Deep Eutectic Solvents (DESs). Among the tested formulations, a mixture of Choline Chloride and Glycerol (ChCl:Gly, 1:2 molar ratio, containing 30% v/v water) exhibited outstanding extraction efficiency, significantly outperforming conventional organic solvents such as aqueous ethanol and methanol. Quantitative high-performance liquid chromatography with diode-array detection (HPLC-DAD) confirmed the enrichment of key flavone glycosides, specifically luteolin-7-O-glucoside and apigenin-7-O-glucoside, in the DES extract. To explore the pharmaceutical potential of the integrated extract, in vitro anti-inflammatory assays targeting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were performed. Strikingly, combinations of the S. scardica DES extract with standard non-steroidal anti-inflammatory drugs (NSAIDs), namely ibuprofen and diclofenac, were systematically evaluated using the Chou-Talalay median-effect method. The combination index (CI) values revealed a strong, dose-dependent synergism (CI < 1.0) between the phytochemical extract and both NSAIDs. This synergism resulted in a favorable Dose-Reduction Index (DRI), suggesting that co-administration of S. scardica flavonoids could substantially lower the therapeutic dosage of synthetic NSAIDs, thereby potentially minimizing their notorious gastrointestinal and cardiovascular side effects. These findings highlight the potential of integrating green extraction chemistry with modern pharmacodynamics to design safer, multi-target anti-inflammatory therapeutic systems.
