title: Administration of 4-(α-L-rhamnosyloxy)-benzyl isothiocyanate delays disease phenotype in SOD1(G93A) rats: a transgenic model of amyotrophic lateral sclerosis.
abstract: 4-(α-L-Rhamnosyloxy)-benzyl glucosinolate (glucomoringin, GMG) is a compound found in Moringa oleifera seeds. Myrosinase-catalyzed hydrolysis at neutral pH of GMG releases the biologically active compound 4-(α-L-rhamnosyloxy)-benzyl isothiocyanate (GMG-ITC). The present study was designed to test the potential therapeutic effectiveness of GMG-ITC to counteract the amyotrophic lateral sclerosis (ALS) using SOD1tg rats, which physiologically develops SOD1(G93A) at about 16 weeks of life, and can be considered a genetic model of disease. Rats were treated once a day with GMG (10 mg/Kg) bioactivated with myrosinase (20 µL/rat) via intraperitoneal (i.p.) injection for two weeks before disease onset and the treatment was prolonged for further two weeks before the sacrifice. Immune-inflammatory markers as well as apoptotic pathway were investigated to establish whether GMG-ITC could represent a new promising tool in clinical practice to prevent ALS. Achieved data display clear differences in molecular and biological profiles between treated and untreated SOD1tg rats leading to guessing that GMG-ITC can interfere with the pathophysiological mechanisms at the basis of ALS development. Therefore, GMG-ITC produced from myrosinase-catalyzed hydrolysis of pure GMG could be a candidate for further studies aimed to assess its possible use in clinical practice for the prevention or to slow down this disease.
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
authors.forename: Maria
authors.identifier: 0000-0002-6544-576X
authors.initials: M
authors.lastname: Galuppo
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
authors.forename: Sabrina
authors.identifier: 0000-0002-4793-6725
authors.initials: S
authors.lastname: Giacoppo
authors.affiliation: Council for Agricultural Research and Economics-Research Centre for Industrial Crops (CRA-CIN), Via di Corticella 133, 40128 Bologna, Italy.
authors.forename: Renato
authors.identifier: 0000-0002-2493-6941
authors.initials: R
authors.lastname: Iori
authors.affiliation: Council for Agricultural Research and Economics-Research Centre for Industrial Crops (CRA-CIN), Via di Corticella 133, 40128 Bologna, Italy.
authors.forename: Gina Rosalinda
authors.initials: GR
authors.lastname: De Nicola
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
authors.forename: Placido
authors.identifier: 0000-0003-0394-8166
authors.initials: P
authors.lastname: Bramanti
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006026:Glycoside Hydrolases / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D050505:Mutant Proteins / Q000235:genetics; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012210:Rhamnose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: C000600309:4-((alpha-L-rhamnosyloxy)benzyl)isothiocyanate; D017879:Isothiocyanates; D050505:Mutant Proteins; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D006026:Glycoside Hydrolases; C022739:thioglucosidase; D012210:Rhamnose