Molecular Neurobiology

, Volume 54, Issue 8, pp 5961–5972 | Cite as

Carnosic Acid Protects Mitochondria of Human Neuroblastoma SH-SY5Y Cells Exposed to Paraquat Through Activation of the Nrf2/HO-1Axis

  • Marcos Roberto de OliveiraEmail author
  • Alessandra Peres
  • Gustavo Costa Ferreira
  • Patrícia Fernanda Schuck
  • Clarissa S. Gama
  • Simone Morelo Dal Bosco


Carnosic acid (CA; C20H28O4), which is also called salvin, is a major phenolic diterpene found in Rosmarinus officinalis L. and exhibits antioxidant, anti-inflammatory, and antiproliferative properties. CA activates the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, leading to the upregulation of antioxidant and phase II detoxification enzymes, such as heme oxygenase-1 (HO-1), glutathione reductase (GR), γ-glutamate-cysteine ligase (γ-GCL), and glutathione S-transferase (GST), among others. We have previously demonstrated that CA upregulates the total and mitochondrial synthesis of glutathione (GSH), causing mitochondrial protection against paraquat (PQ) and methylglyoxal (MG). Nonetheless, the complete mechanism by which CA prevented mitochondrial dysfunction was not clear yet. Here, we examine whether HO-1 would be involved in the CA-induced mechanism of mitochondrial protection in SH-SY5Y-treated cells. SH-SY5Y cells were pretreated with CA (1 μM) for 12 h prior to a challenge with PQ at 100 μM for additional 24 h. Zinc protoporphyrin IX (ZnPP IX; a specific inhibitor of HO-1; 10 μM) was utilized prior to exposure to CA in order to investigate whether HO-1 was involved in the cytoprotective effects elicited by CA. We found that the CA-induced Nrf2-dependent HO-1 upregulation ameliorated, at least in part, the mitochondrial function in PQ-treated cells. Therefore, CA protected mitochondria of SH-SY5Y cells and exerted anti-apoptotic effects by activating the Nrf2/HO-1 axis.


Carnosic acid Mitochondria Antioxidant Anti-apoptotic HO-1 



This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). PFS and CSG receive a “CNPq Produtividade em Pesquisa” fellow. GCF is supported by Edital APQ1/FAPERJ and by CNPq.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Marcos Roberto de Oliveira
    • 1
    Email author
  • Alessandra Peres
    • 2
    • 3
  • Gustavo Costa Ferreira
    • 4
  • Patrícia Fernanda Schuck
    • 5
  • Clarissa S. Gama
    • 6
    • 7
  • Simone Morelo Dal Bosco
    • 8
  1. 1.Department of Chemistry/ICETFederal University of Mato Grosso (UFMT)CuiabaBrazil
  2. 2.Departamento de Ciências Básicas da SaúdeUniversidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA)Porto AlegreBrazil
  3. 3.Centro de Pesquisa da Pós-GraduaçãoCentro Universitário Metodista IPAPorto AlegreBrazil
  4. 4.Instituto de Bioquímica Médica Leopoldo de MeisUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  5. 5.Laboratório de Erros Inatos do Metabolismo, Unidade Acadêmica de Ciências da Saúde, Programa de Pós-Graduação em Ciências da SaúdeUniversidade do Extremo Sul Catarinense (UNESC)CriciúmaBrazil
  6. 6.Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre (HCPA)Instituto Nacional de Ciência e Tecnologia - Medicina Translacional (INCT-TM)Porto AlegreBrazil
  7. 7.Programa de Pós-Graduação em Medicina: PsiquiatriaUniversidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  8. 8.Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA)Porto AlegreBrazil

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