Molecular Neurobiology

, Volume 54, Issue 6, pp 4597–4608 | Cite as

Tanshinone I Induces Mitochondrial Protection through an Nrf2-Dependent Mechanism in Paraquat-TreatedHuman Neuroblastoma SH-SY5Y Cells

  • Marcos Roberto de OliveiraEmail author
  • Patrícia Fernanda Schuck
  • Simone Morelo Dal Bosco


Tanshinone I (T-I; 1,6-Dimethylnaphtho[1,2-g][1]benzofuran-10,11-dione; C18H12O3), which may be found in Salvia miltiorrhiza Bunge (Danshen), is a potent anti-inflammatory, antioxidant, and anti-cancer agent. At least in part, T-I exerts antioxidant activity by activating signaling pathways associated with the maintenance of the redox state in mammalian cells. In this context, the upregulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has received attention regarding the role of this transcription factor in modulating the expression of antioxidant enzymes and the metabolism of glutathione (GSH). Even though there is a growing body of evidence suggesting that T-I mediates protection against several pro-oxidant challenges in both in vitro and in vivo experimental models, it remains to be examined whether and how T-I would modulate mitochondrial function during redox disturbances. Therefore, we aimed to reveal whether T-I would exhibit protective effects on mitochondria of SH-SY5Y cells treated with paraquat (PQ), a well-known mitochondrial toxic agent. We found that T-I pretreatment significantly protected mitochondria against PQ-induced redox impairment through an Nrf2-dependent mechanism involving upregulation of antioxidant enzymes, such as Mn-superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx), and both catalytic and modifier subunits of γ-glutamate-cysteine ligase (γ-GCL). T-I prevented complex I and mitochondrial membrane potential (MMP) impairments elicited by PQ. Thus, T-I may be viewed as a new mitochondrial protective agent whose complete mechanism of action needs to be investigated, but it seems to involve mitochondriotropic aspects related to the chemistry of this molecule.


Tanshinone I Paraquat Mitochondria Nrf2 Antioxidant 



This work was partially supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). PFS is recipient of a CNPq fellow (Bolsista de Produtividade em Pesquisa 2—CA BF).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Role of the Funding Source

The sponsors of this work had no role in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the article for publication.

Supplementary material

12035_2016_9_MOESM1_ESM.pdf (108 kb)
Figure S1 The effects of paraquat (PQ) at different concentrations for 24 h on cell viability (A), cytotoxicity (B), and ROS production (C). (D) Cell viability of SH-SY5Y cells exposed to PQ at 100 μM for different periods. Data are presented as the mean ± SEM of three or five independent experiments each done in triplicate. One-way ANOVA followed by the post hoc Tukey’s test, *p < 0.05 vs the control group. (PDF 107 kb)
12035_2016_9_MOESM2_ESM.pdf (105 kb)
Figure S2 The effects of a pretreatment with tanshinone-I (T-I) at 1–5 μM for 2 h on cell viability (A), cytotoxicity (B), and ROS production (C). Data are presented as the mean ± SEM of three or five independent experiments each done in triplicate. One-way ANOVA followed by the post hoc Tukey’s test, *p < 0.05 vs the control group, # p < 0.05 different from PQ-treated group, a p < 0.01 different from PQ-treated cells. (PDF 105 kb)
12035_2016_9_MOESM3_ESM.pdf (111 kb)
Figure S3 The effects of a pretreatment with T-I at 2.5 μM for 2 h on (A) Bax immunocontent, (B) Bcl-2 immunocontent, (C) cytosolic cytochrome c content, (D) caspase-9 activity, (E) caspase-3 activity, and (F) DNA fragmentation. PQ was utilized at 100 μM for 24 h. Data are presented as the mean ± SEM of three or five independent experiments each done in triplicate. One-way ANOVA followed by the post hoc Tukey’s test, * p < 0.05 vs control cells, a p < 0.05 vs the cells treated with either PQ or T-I alone. (PDF 111 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Marcos Roberto de Oliveira
    • 1
    Email author
  • Patrícia Fernanda Schuck
    • 2
  • Simone Morelo Dal Bosco
    • 3
  1. 1.Programa de Pós-Graduação em Química, Departamento de Química (DQ), Instituto de Ciências Exatas e da Terra (ICET)Universidade Federal de Mato Grosso (UFMT)CuiabáBrazil
  2. 2.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 SaúdeCriciúmaBrazil
  3. 3.Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA)Porto AlegreBrazil

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