title: Neuroprotective effects of phloretin and its glycosylated derivative on rotenone-induced toxicity in human SH-SY5Y neuronal-like cells.
abstract: Phloretin and phlorizin are the two strong natural antioxidants whose biological and pharmacological applications are rapidly growing in different human pathological conditions. The neuroprotective activity of the two flavonoids has been analyzed on cell culture of neuroblastoma cells. The neuroprotective activity of the two flavonoids has been analyzed on cell culture of neuroblastoma cells and evaluated by testing cell vitality, mitochondrial transmembrane potential and ROS production, antioxidant enzymes detection, activation of caspase 3, DNA damage, protein carbonylation, lipid peroxidation, and superoxide anion scavenging activity. Incubation of cells with rotenone caused cell death and significant increase in intracellular reactive oxygen species, activation of caspase 3, and variation in mitochondrial transmembrane potential. Although, rotenone exposure caused a significant increase of antioxidant enzymes, high levels of lipid peroxidation were also observed. Phloretin or phlorizin, at micromolar concentration, reduced rotenone-induced cell death by scavenging ability against superoxide anion radical, one of the main effectors of rotenone toxicity at level of mitochondrial respiratory chain complex I. Under our experimental conditions, a reduction of the intracellular ROS levels with consequent normalization of the aforementioned antioxidant enzymes occurred. Concomitantly, we observed the inhibition of caspase 3 activity and DNA damage. This study shows the promising neuroprotective ability of the two dihydrochalcones able to protect human differentiated neuroblastoma cells (commonly used as model of Parkinson's disease) from injury induced by rotenone, actively scavenging ROS, normalizing mitochondrial transmembrane potential and consequently avoiding energy depletion. © 2017 BioFactors, 43(4):549-557, 2017.
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Barreca
authors.affiliation: Department of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, Polyclinic Hospital University, Via C. Valeria, Messina, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Currò
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Ersilia
authors.initials: E
authors.lastname: Bellocco
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Ficarra
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Laganà
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Tellone
authors.affiliation: Department of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, Polyclinic Hospital University, Via C. Valeria, Messina, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Laura Giunta
authors.affiliation: Department of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, Polyclinic Hospital University, Via C. Valeria, Messina, Italy.
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Visalli
authors.affiliation: Department of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, Polyclinic Hospital University, Via C. Valeria, Messina, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Caccamo
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Galtieri
authors.affiliation: Department of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, Polyclinic Hospital University, Via C. Valeria, Messina, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ientile
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D005419:Flavonoids / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010693:Phloretin / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*
chemical_list: D005419:Flavonoids; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D012402:Rotenone; D010693:Phloretin
keywords: flavonoids; neuroprotective activity; phloretin; phlorizin; superoxide anion