Neuroprotective effect of steroidal alkaloids on glutamate-induced toxicity by preserving mitochondrial membrane potential and reducing oxidative stress

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Marcos Taveira (Author) Other; Carla Sousa (Author) Other; Patricia Valentao (Author) FFUP; Federico Ferreres (Author) Other; Joao P Teixeira (Author) Other; Paula B Andrade (Author) FFUP

Journal

Title: Journal of Steroid Biochemistry and Molecular Biology

Vol. 140

Pages: 106-115

ISSN: 0960-0760

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 30 Citations

Scopus - 37 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-008-YXV

DOI: 10.1016/j.jsbmb.2013.12.013

Abstract (EN): 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 alpha 7 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10