LC–HRESIMS-Guided Phytochemical Characterization and Bioactivity Evaluation of Filipendula hexapetala Gilib. From Algeria: Antioxidant and Anticholinesterase Potential Supported by In Silico Analysis

Abstract

Filipendula hexapetala Gilib., a medicinal plant native to Sétif, Northeastern Algeria, holds therapeutic potential, though itsbioactive constituents remain underexplored. This study provides the first comprehensive analysis of its chemical composition andbiological activities. The hydromethanolic extract obtained from aerial parts was analyzed using LC–HRESIMS for qualitative andquantitative phytochemical profiling. The antioxidant activity was assessed using five different assays, while the anticholinesteraseactivity was evaluated through in vitro enzyme inhibition tests. In addition, density functional theory (DFT) calculations andmolecular docking were conducted to explore the electronic properties and binding affinities of key flavonoids. Chemicalprofiling revealed considerable phytochemical diversity, with hyperoside identified as the predominant compound. The extractdemonstrated strong antioxidant activity, particularly in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 14.93 ± 0.35 mg/L) and2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (IC50 = 112.11 ± 3.34 mg/L) assays. Although the extract exhibitedonly weak anticholinesterase activity, molecular docking showed that key flavonoids had significant affinity for both humanacetylcholinesterase (hAChE) and human butyrylcholinesterase (hBuChE) active sites. DFT calculations elucidated the moststable molecular geometries and provided valuable predictions regarding the chemical stability and electronic properties of thesecompounds. 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.