Neuroprotective activity of isoquinoline alkaloids from of Chilean Amaryllidaceae plants against oxidative stress-induced cytotoxicity on human neuroblastoma SH-SY5Y cells and mouse hippocampal slice culture.

In this study we evaluate the chemical composition and neuroprotective effects of alkaloid fractions of the Amaryllidaceae species Rhodophiala pratensis, Rhodolirium speciosum, Phycella australis and Phaedranassa lehmannii. Gas chromatography-mass spectrometry (GC/MS) enable the identification of 41 known alkaloids. Rhodolirium speciosum and Rhodophiala pratensis were the most active extracts against acetylcholinesterase (AChE), with IC₅₀ values of 35.22 and 38.13 μg/mL, respectively. The protective effect of these extracts on human neuroblastoma cells (SH-SY5Y) subjected to mitochondrial oxidative stress with rotenone/oligomycin A (R/O) and toxicity promoted by okadaic acid (OA) was evaluated. Only Phycella australis and Rhodophiala pratensis at 0.75 and 1.5 μg/mL, tend to reverse the cell death induced by R/O by around 12%. In OA assay, alkaloid fractions of Phycella Australis and Phaedranassa lehmannii displayed a concentration-dependent (0.375-3.0 μg/mL) effect with a maximum neuroprotective response of 78% and 84%, respectively. Afterwards, neuroprotective effects of Phycella australis (3 and 6 μg/mL) in mouse hippocampal slices stressed with oxygen glucose deprivation/reoxygenation (OGD/R), shown a protection greater than 14%. Finally, Phycella Australis (6 μg/mL) reverted the cell viability from 65% to 90% in slices treated with OA, representing a protection of 25% attributable to the alkaloids of this species.