title: Neuroprotective effect of steroidal alkaloids on glutamate-induced toxicity by preserving mitochondrial membrane potential and reducing oxidative stress.
abstract: Several evidences suggest that enhanced oxidative stress is involved in the pathogenesis and/or progression of several neurodegenerative diseases. The aim of this study was to investigate for the first time whether both extracts from tomato plant (Lycopersicon esculentum Mill.) leaves and their isolated steroidal alkaloids (tomatine and tomatidine) afford neuroprotective effect against glutamate-induced toxicity in SH-SY5Y neuroblastoma cells and to elucidate the mechanisms underlying this protection. Steroidal alkaloids from tomato are well known for their cholinesterases' inhibitory capacity and the results showed that both purified extracts and isolated compounds, at non-toxic concentrations for gastric (AGS), intestinal (Caco-2) and neuronal (SH-SY5Y) cells, have the capacity to preserve mitochondria membrane potential and to decrease reactive oxygen species levels of SH-SY5Y glutamate-insulted cells. Moreover, the use of specific antagonists of cholinergic receptors allowed observing that tomatine and tomatidine can interact with nicotinic receptors, specifically with the α7 type. No effect on muscarinic receptors was noticed. In addition to the selective cholinesterases' inhibition revealed by the compounds/extracts, these results provide novel and important insights into their neuroprotective mechanism. This work also demystifies the applicability of these compounds in therapeutics, by demonstrating that their toxicity was overestimated for long time.
authors.affiliation: REQUIMTE/Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, n°. 228, 4050-313 Porto, Portugal.
authors.forename: Marcos
authors.initials: M
authors.lastname: Taveira
authors.affiliation: REQUIMTE/Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, n°. 228, 4050-313 Porto, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Sousa
authors.affiliation: REQUIMTE/Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, n°. 228, 4050-313 Porto, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Valentão
authors.affiliation: CEBAS (CSIC) Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, P.O. Box 164, 30100 Campus University Espinardo, Murcia, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Ferreres
authors.affiliation: Environmental Health Department, National Institute of Health, Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal.
authors.forename: João P
authors.initials: JP
authors.lastname: Teixeira
authors.affiliation: REQUIMTE/Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, n°. 228, 4050-313 Porto, Portugal. Electronic address: pandrade@ff.up.pt.
authors.forename: Paula B
authors.initials: PB
authors.lastname: Andrade
mesh_terms: D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D014053:Tomatine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D010936:Plant Extracts; C003677:tomatidine; D014053:Tomatine; D018698:Glutamic Acid
keywords: Cholinergic receptors; Mitochondrial membrane potential; Neuroprotection; Oxidative stress; Steroidal alkaloids