Abstract
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. In-silico 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-1; ROSIC50 = 4.4 μg mL-1), anti-cholinesterase (AChEIC50 = 137.1 vg L-1; BChEIC50 = 147.0 μg mL-1) and anti-inflammatory properties (against IL-6 and LOXIC50 = 76.1 μg mL-1), with low cytotoxicity and protection against L-glutamic acid in cell models.