Optimization and Chemical Characterization of Extracts Obtained from Ferula persica var. latisecta Aerial Parts and Roots and Their Neuroprotective Evaluation.

Background/Objectives: The genus Ferula has been traditionally used for the treatment of various illnesses, but the potential of Ferula persica var. latisecta against different Alzheimer's disease (AD) hallmarks has never been achieved. Methods: In this work, a pressurized liquid extraction (PLE) method was optimized to extract F. persica L. aerial parts and roots. Four different solvents (water, ethanol, ethyl acetate (EtAc), and cyclopentyl methyl ether (CPME)) were first tested, and the extraction yield, total phenolic content, reactive oxygen species scavenging capacity, and acetylcholinesterase (AChE) inhibition activity were evaluated. Results: The results indicated that EtAc and CPME were the best solvents to be used, with the results obtained from the aerial parts being better than those obtained from the root samples. Thereafter, the PLE method was further optimized by combining these solvents in different percentages (100% EtAc, 100% CPME, and 50:50% (v/v) EtAc:CPME) and temperatures (50, 115, and 180 °C). Response surface methodology was then applied to analyze the data, and two optimum extraction conditions were obtained: EtAc:CPME (79:21%) at 180 °C for the aerial parts and 100% CPME at 180 °C for the roots. At these conditions, the total flavonoid content (TFC) and the inhibitory capacities against butyrylcholinesterase (BChE) and lipoxygenase (LOX) enzymes were also evaluated, indicating that the aerial part extracts had higher TFC and LOX inhibitory capacity than the root extracts but lower activity against BChE. The comprehensive LC/GC-MS chemical characterization allowed for the tentative identification of 222 compounds belonging to 66 chemical subclasses, the abundancies of which widely varied depending on the matrix and the extraction conditions used. Conclusions: The results obtained together with the application of advanced statistical analysis and molecular docking simulations suggested several sesquiterpenoids, such as selina-3,7(11)-diene, guaiol acetate, α-cyperone, and farnesyl acetate, as the molecules responsible of the in vitro results observed, with good neuroprotective potential against AD. [ABSTRACT FROM AUTHOR]