Sequential Obtention of Blood-Brain Barrier-Permeable Non-Polar and Polar Compounds from L. and Labill. with Neuroprotective Purposes.

This study investigates the biorefinery approach to extracting blood-brain barrier (BBB)-permeable compounds from Labill. and L. for neuroprotective purposes. A sequential extraction process was applied, starting with supercritical CO extraction (SC-CO) to obtain non-polar terpenoids, followed by pressurized natural deep eutectic solvent extraction (PLE-NaDES) to recover phenolic compounds from the SC-CO residue. PLE-NaDES extracts exhibited higher antioxidant and anticholinergic capacities than SC-CO extracts for both plants, with extracts being more bioactive than extracts. A total of 21 terpenoids were identified using gas chromatography-mass spectrometry from while 24 were detected from SC-CO extracts. In addition, 25 different phenolic compounds were identified in both plants using high-performance liquid chromatography coupled with mass spectrometry from PLE-NaDES extracts. The study of the permeability across the BBB showed limited permeability for non-polar compounds obtained by SC-CO from both plants; however, the more polar compounds obtained by PLE-NaDES showed high permeability, particularly for flavonoids in and rosmarinic acid in . This study revealed, for the first time, the antioxidant and neuroprotective potential of and extracts obtained using SC-CO followed by PLE-NaDES, as well as the high permeability of PLE-NaDES extracts when crossing the BBB to exert their protective effects. This research opens a new pathway for exploring alternatives to current drugs used in treating neurodegenerative diseases.