Phenolic composition and multi‐target bioactivities of <i>Globularia alypum</i> extracts across seasons

Abstract Background This study investigates the influence of seasonal variation on the phytochemical profile and biofunctional activities of ethanolic leaf extracts from Globularia alypum . Leaves collected across four seasons were extracted with a hydroethanolic solvent (80:20, v/v) and analyzed by LC‐ESI‐MS/MS. Total phenolic and flavonoid contents were determined using Folin–Ciocalteu and aluminum chloride assays, while antioxidant capacity was evaluated using five complementary methods (DPPH, ABTS, ADS, FRAP, and SNPAC). Anti‐inflammatory, analgesic, enzyme‐inhibitory, antimicrobial, photoprotective, and acute oral toxicity (OECD 423) activities were also assessed. Trans‐cinnamic acid and trans‐ferulic acid were identified as major constituents across all seasons. Results Spring and winter extracts showed the highest phenolic and flavonoid levels and exhibited stronger antioxidant activity, particularly in ABTS, ADS, and SNPAC assays, together with significant anti‐inflammatory and antinociceptive effects. The spring extract produced 76.81% inhibition of nociceptive behavior at 500 mg/kg and 74.90% inhibition of carrageenan‐induced edema, comparable to reference drugs. All extracts displayed high in vitro photoprotective potential (SPF 31.25–34.90), while antimicrobial activity was negligible. Notably, the summer extract showed strong urease‐inhibitory activity (IC 50 = 15.25 μg/mL), comparable to thiourea (IC 50 = 11.57 μg/mL), despite having the lowest phenolic content. No acute toxicity was observed up to 2000 mg/kg. Conclusion These findings demonstrate that harvest season significantly influences the phytochemical composition and biological properties of G. alypum , highlighting its potential as a source of bioactive compounds for further pharmacological investigation.