Lipophilic Compounds from Tunisian Sarcocornia fruticosa: Characterization, Acetylcholinesterase Docking and Drug-likeness Evaluation

Abstract

Sarcocornia fruticosa is a halophytic shrub from coastal salt marshes valued for its ecological role and rich content of minerals and bioactive compounds. This study combined pharmacokinetic, in silico, and in vitro approaches to evaluate the antioxidant potential of its lipophilic extract. Gas chromatography/mass spectrometry identified 22 lipophilic compounds, mainly saturated and polyunsaturated fatty acids (62%), followed by alcohols (13%), hydrocarbons (8%), and phytosterols (7%). LE exhibited moderate antioxidant and anti-acetylcholinesterase (AChE) activities, with half maximal inhibitory concentration (IC₅₀) values of 479 µg/mL 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, 566 µg/mL ferric reducing antioxidant power (FRAP) assay, 672 µg/mL NO^• scavenging assay and 588 µg/mL anti-AChE activity. Docking studies highlighted phytosterols (stigmasterol, δ-sitosterol, stigmastanol) as the strongest AChE inhibitors, followed by phytol, while fatty acids andhydrocarbons showed weak binding due to poor fit within the catalytic gorge. Pharmacokinetic analyses revealed significant limitations: phytosterols exhibited poor gastrointestinal absorption, high molar mass, rigidity, and low polarity, violating several drug-likeness filters. Phytol showed a slightly better profile due to its lower molar mass and flexibility, but its high lipophilicity and low solubility may still limit absorption. All four compounds were predicted as P-glycoprotein substrates, indicating reduced systemic exposure, and potential CYP2C9 inhibition suggested possible drug–drug interactions. Overall, integrating these approaches provides a comprehensive view of the bioactivity and pharmacokinetic constraints of S. fruticosa lipophilic compounds.