Neuroprotective potential of terpenoid-rich extracts from orange juice by-products obtained by pressurized liquid extraction.

Pressurized liquid extraction (PLE) conditions were optimized to improve the recovery of orange (Citrus sinensis) by-products terpenoids. The neuroprotective potential of the PLE extracts were tested against a set of in-vitro assay (antioxidant (ABTS), reactive oxygen/nitrogen species (ROS/RNS)) as well as enzymatic tests (acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and lipoxygenase (LOX)). Gas chromatography coupled to high-resolution mass spectrometry (GC-q-TOF-MS) analysis revealed a higher enrichment in mono- and sesquiterpenoids of the PLE extracts with the highest neuroprotection capacity. molecular docking analysis showed the specific interaction of representative terpenoids with enzymes active sites. The results demonstrate that the selected extract at 100 °C and 30 minutes possesses high antioxidant (ABTSIC50 = 13.5 μg mL; ROSIC50 = 4.4 μg mL), anti-cholinesterase (AChEIC50 = 137.1 vg  L; BChEIC50 = 147.0 μg mL) and anti-inflammatory properties (against IL-6 and LOXIC50 = 76.1 μg mL), with low cytotoxicity and protection against L-glutamic acid in cell models.