Comparative analysis of phytochemical content and antioxidants, anti-cholinesterase, Anti-Atherogenic and molecular docking of Turkish Pelargonium (Pelargonium endlicherianum Fenzl.)

Pelargonium endlicherianum Fenzl, a perennial shrub in the Geraniaceae family, holds ethnobotanical importance. This study is the first to evaluate the acetylcholinesterase (AChE) and paraoxonase (hPON1) inhibitory activities, alongside the antioxidant properties, of P. endlicherianum extracts. Using LC-MS/MS, 25 phenolic compounds were quantified, with ellagic acid (20,449.65 ± 0.60 mg/kg), gallic acid (9,700.31 ± 0.03 mg/kg), and fumaric acid (1,691.34 ± 33.34 mg/kg) as the dominant bioactive components. Antioxidant assays (DPPH•, ABTS•+, FRAP, and CUPRAC) demonstrated that the ultrapure water extract exhibited superior activity, with a DPPH• scavenging capacity of 75.06 ± 0.73% at 0.2 mg/mL. The ultrapure water extract significantly inhibited AChE with an IC₅₀ value of 0.135 ± 0.29 mg/mL, while no inhibition of hPON1 was observed, indicating an anti-atherogenic effect. Molecular docking analysis revealed ellagic acid as the most potent compound, with a binding affinity of -10.0 kcal/mol, outperforming the reference inhibitor tacrine (-8.6 kcal/mol). Gene network analysis supported the involvement of ellagic acid, gallic acid , and fumaric acid in Alzheimer's disease-related pathways. These findings suggest that P. endlicherianum extracts possess significant antioxidant and AChE inhibitory properties, making them promising candidates for therapeutic applications, particularly in neurodegenerative disorders. • Strong AChE inhibition (Alzheimer's target),. • No effect on paraoxonase (no atherosclerosis risk),. • Active phenolics: ellagic acid, gallic acid, fumaric acid (main contributors), plus quercetin , kaempferol , caffeic acid , and syringic acid ,. • Ellagic acid identified as the most effective for AChE inhibition,. • Supports iron regulation in Alzheimer's plaques and neurofibrils .