title: Protective effect of carnosic acid against paraquat-induced redox impairment and mitochondrial dysfunction in SH-SY5Y cells: Role for PI3K/Akt/Nrf2 pathway.
abstract: Carnosic acid (CA) is a phenolic diterpene isolated from Rosmarinus officinalis and exerts anti-inflammatory, antioxidant, and anticarcinogenic activities in different cell types. It has been reported that CA is able to cause protective effects on experimental models of neurodegeneration. However, the exact mechanism by which CA prevents neuronal degeneration remains to be better studied. We investigated here whether there is a role for CA as a neuroprotective agent in a paraquat (PQ) model of Parkinson's disease (PD) regarding cellular and mitochondrial-related redox parameters. SH-SY5Y cells were treated with CA for 12h and were exposed to 100 μM PQ for 24h. It was found that CA at different concentrations prevented the effects of PQ on cell viability and redox parameters. CA alleviated reactive oxygen and nitrogen species production elicited by PQ, as well as decreased the toxic effect on mitochondrial function. Inhibition of Pi3K/Akt pathway with LY294002 or silencing of Nrf2 expression partially blocked the reversal of redox impairment induced by CA. Therefore, CA activated Nrf2 through modulation of PI3K/Akt pathway resulting in increased levels of antioxidant enzymes and consequent neuroprotection. Thus, CA may be viewed as a potential neuroprotective agent to be used in cases of Parkinson's disease (PD).
authors.affiliation: Programa de Pós-Graduação em Química, Departamento de Química (DQ), Instituto de Ciências Exatas e da Terra (ICET), Universidade Federal de Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP 78060-900 Cuiabá, MT, Brazil. Electronic address: mrobioq@gmail.com.
authors.forename: Marcos Roberto
authors.initials: MR
authors.lastname: de Oliveira
authors.affiliation: Laboratório de Erros Inatos do Metabolismo, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense (UNESC), Programa de Pós-Graduação em Ciências da Saúde, Criciúma, SC, Brazil.
authors.forename: Gustavo Costa
authors.initials: GC
authors.lastname: Ferreira
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
authors.forename: Patrícia Fernanda
authors.initials: PF
authors.lastname: Schuck
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010269:Paraquat; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D045784:Abietanes; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D005978:Glutathione; C018381:salvin; D010269:Paraquat
keywords: Akt; Carnosic acid; Mitochondria; Nrf2; Oxidative stress; Paraquat