Bousetla_2025_Chem.Biodivers__e01270

Filipendula hexapetala Gilib., a medicinal plant native to Setif, Northeastern Algeria, holds therapeutic potential, though its bioactive constituents remain underexplored. This study provides the first comprehensive analysis of its chemical composition and biological activities. The hydromethanolic extract obtained from aerial parts was analyzed using LC-HRESIMS for qualitative and quantitative phytochemical profiling. The antioxidant activity was assessed using five different assays, while the anticholinesterase activity was evaluated through in vitro enzyme inhibition tests. In addition, density functional theory (DFT) calculations and molecular docking were conducted to explore the electronic properties and binding affinities of key flavonoids. Chemical profiling revealed considerable phytochemical diversity, with hyperoside identified as the predominant compound. The extract demonstrated strong antioxidant activity, particularly in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC(50) = 14.93 +/- 0.35 mg/L) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (IC(50) = 112.11 +/- 3.34 mg/L) assays. Although the extract exhibited only weak anticholinesterase activity, molecular docking showed that key flavonoids had significant affinity for both human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBuChE) active sites. DFT calculations elucidated the most stable molecular geometries and provided valuable predictions regarding the chemical stability and electronic properties of these compounds. These results provide the first detailed insight into the phytochemical and biological properties of F. hexapetala, highlighting its potent antioxidant effects and assessing its potential neuroprotective activities.