Process Optimization of Solidago canadensis Extracts: Impact on Polyphenolic Profile, Antioxidant Capacity, and Cytotoxic Activity

Optimizing the extraction of bioactive compounds from Solidago sp. is essential for the development of plant-derived products with therapeutic and nutraceutical potential. Microwave-assisted (MW) and thermal maceration (TM) extraction of S. canadensis aerial parts were comparatively investigated to maximize total flavonoid content (TFC). The obtained extracts were subsequently freeze-dried for storage prior to chemical and biological analyses. Extraction conditions were optimized using a Box–Behnken design. Chemical characterization was performed by FTIR, HPLC-PDA, LC-MS/MS, and GC-MS, enabling detailed profiling of phenolic compounds and terpenoids. Antioxidant capacity was assessed using the DPPH radical scavenging assay, while cytotoxic activity was evaluated against HepG2, HCT-8, and HT-29 tumor cell lines, with HEK-293 cells used as a non-tumorigenic control cell line. Multivariate analysis (PCA) was applied to establish relationships between phytochemical composition and biological responses. Higher TFC values were obtained using MW extraction, whereas TM extracts exhibited greater antioxidant activity. Both extract types induced selective cytotoxic effects against tumor cell lines, while maintaining negligible toxicity toward normal HEK-293 cells. PCA revealed distinct clustering patterns between MW and TM extracts and confirmed a strong association between phenolic composition and bioactivity. The combination of optimized extraction, freeze-drying, and integrated chemical–biological evaluation produced S. canadensis extracts with well-defined phytochemical profiles and biological activity, supporting their potential use in nutraceutical, and pharmaceutical applications.