Sequential Obtention of Blood–Brain Barrier-Permeable Non-Polar and Polar Compounds from Salvia officinalis L. and Eucalyptus globulus Labill. with Neuroprotective Purposes

This study investigates the biorefinery approach to extracting blood–brain barrier (BBB)-permeable compounds from Eucalyptus globulus Labill. and Salvia officinalis L. for neuroprotective purposes. A sequential extraction process was applied, starting with supercritical CO₂ extraction (SC-CO₂) to obtain non-polar terpenoids, followed by pressurized natural deep eutectic solvent extraction (PLE-NaDES) to recover phenolic compounds from the SC-CO₂ residue. PLE-NaDES extracts exhibited higher antioxidant and anticholinergic capacities than SC-CO₂ extracts for both plants, with S. officinalis extracts being more bioactive than E. globulus extracts. A total of 21 terpenoids were identified using gas chromatography–mass spectrometry from E. globulus while 24 were detected from S. officinalis SC-CO₂ 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-CO₂ from both plants; however, the more polar compounds obtained by PLE-NaDES showed high permeability, particularly for flavonoids in E. globulus and rosmarinic acid in S. officinalis. This study revealed, for the first time, the antioxidant and neuroprotective potential of S. officinalis and E. globulus extracts obtained using SC-CO₂ 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.