"Purple Rain, Purple Rain": RSM Optimization and Bioactivity Assessment of Rosmarinic Acid-Rich Salvia verticillata L. Ethanolic Root Extract.

Despite the well-established bioactivity of Salvia verticillata L. aerial parts, their roots represent an unexplored plant matrix. In this study, root extracts obtained by ethnopharmacological (EE), maceration (ME), and ultrasound-assisted (UE) extraction were examined. Ultrasound-assisted extraction was optimized using response surface methodology (RSM, CCD) to maximize total phenolic content (TPC) and rosmarinic acid (RA), and the optimized extract was compared with EE and ME. All extracts exhibited high levels of total phenolics, flavonoids, and phenolic acids, while RA was the dominant compound according to HPLC analysis (96.67-137.47 mg g-1 d.e.). UE yielded the highest TPC and exhibited the strongest antioxidant activity in most of the applied assays. All extracts exhibited concentration-dependent tyrosinase inhibitory activity, with UE and EE showing the strongest effects. Moderate antibacterial activity, particularly against Gram-positive strains, and limited antifungal effects were observed. Strong COX-1 inhibition (>70% at 50 μg/mL) confirmed the anti-inflammatory potential of the extracts, whereas slight COX-2 inhibition was observed. UE exhibited moderate cytotoxic activity against A431, SVT2, and HaCaT cells. These findings identify S. verticillata roots as a promising source of rosmarinic acid-rich extracts and point out the importance of the extraction procedure to tailor the biological activity of the extract.