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

• Published in: Food and chemical toxicology 2019-10, Vol.132, p.110665-110665, Article 110665
• Main Authors: Trujillo-Chacón, Lina M., Alarcón-Enos, Julio E., Céspedes-Acuña, Carlos L., Bustamante, Luis, Baeza, Marcelo, López, Manuela G., Fernández-Mendívil, Cristina, Cabezas, Fabio, Pastene-Navarrete, Edgar R.
• Format: Article
• Language: English
• Subjects: Alkaloids; Alzheimer; Amaryllidaceae; Amaryllidaceae - chemistry; Amaryllidaceae Alkaloids - pharmacology; Animals; Cell Line, Tumor; Gas Chromatography-Mass Spectrometry; Hippocampus - drug effects; Hippocampus - metabolism; Humans; In Vitro Techniques; Isoquinolines - pharmacology; Mice; Mice, Inbred C57BL; Neuroblastoma - metabolism; Neuroblastoma - pathology; Neuroprotective Agents - pharmacology; Oxidative Stress - drug effects
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2019.110665

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. •The inhibitory activity of AChE was evaluated in species Chilean Amarillidaceae species.•Amaryllidaceae alkaloids protected human neuroblastoma cells (SH-SY5Y) from neurotoxicity.•Phycella australis has neuroprotective activity in an OA-induced neurotoxicity model.•Phycella australis protect hippocampal slices in oxygen and glucose deprivation/reoxygenation (OGD/R) model.