Rayene_2026_J.Ethnopharmacol__121997

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants remain an important source of therapeutic agents in traditional medicine. Umbilicus horizontalis (Guss.) DC. (U. horizontalis) is traditionally used in Mediterranean folk medicine as a cicatrizing agent for wound healing and for the treatment of inflammatory conditions and pain. However, its phytochemical composition and pharmacological properties remain largely unexplored. AIM OF THE STUDY: This study aimed to investigate the phytochemical composition of aerial parts of U. horizontalis and to evaluate their antioxidant, analgesic, anti-inflammatory, and neuroprotective activities in order to provide scientific evidence supporting its traditional uses. MATERIALS AND METHODS: Leaves and stems were extracted and fractionated using different solvents. Phytochemical characterization was performed using total phenolic and flavonoid content determination and GC-MS analysis. Antioxidant activity was evaluated using DPPH scavenging, ABTS scavenging, reducing power, and phenanthroline assays. Analgesic activity was assessed using the acetic acid-induced writhing test in mice, while anti-inflammatory activity was evaluated using the xylene-induced ear oedema model. Neuroprotective potential was investigated through acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition assays. RESULTS: Stem crude extract (SCrE) showed the highest phenolic (209.37 +/- 7.98 microg GAE/mg) and flavonoid (87.42 +/- 1.72 microg QE/mg) contents. GC-MS analysis revealed the presence of several terpenoid-related constituents. Antioxidant activity varied according to plant part and solvent, with leaf ethyl acetate extract (LEAE) exhibiting the strongest DPPH scavenging activity (IC(50) = 6.46 +/- 0.22 microg/mL), while stem aqueous extract (SAqE) was most active in the ABTS scavenging assay (IC(50) = 4.67 +/- 0.84 microg/mL). The SCrE also demonstrated strong reducing power and phenanthroline activity (CA(0).(5) = 12.67 +/- 0.91 and 4.96 +/- 0.28 microg/mL, respectively). In vivo assays revealed significant analgesic activity in the acetic acid-induced writhing model, with SCrE producing 87.37% inhibition at 500 mg/kg. LCrE also showed marked anti-inflammatory activity, completely inhibiting xylene-induced ear oedema (100% inhibition) at 250 mg/kg. Furthermore, SCrE exhibited AChE inhibitory activity (IC(50) = 33.72 +/- 1.99 microg/mL), approaching the activity of galantamine (p = 0.9945), while SEAE showed strong BChE inhibition (IC(50) = 3.14 +/- 0.55 microg/mL), significantly higher than galantamine (p < 0.0001). Correlation analysis suggested that phenolic compounds mainly contributed to antioxidant activity, while other metabolites likely underlie enzyme inhibition. CONCLUSION: The pronounced biological activities of U. horizontalis are likely attributed to its high polyphenol and flavonoid content, supporting its traditional medicinal uses. Future research should focus on isolating the active compounds, elucidating their molecular mechanisms, and assessing safety and pharmacokinetics to explore potential therapeutic applications.