Neurotoxicity Research

, Volume 36, Issue 3, pp 491–502 | Cite as

Tanshinone I Induces Mitochondrial Protection by a Mechanism Involving the Nrf2/GSH Axis in the Human Neuroblastoma SH-SY5Y Cells Exposed to Methylglyoxal

  • Cristina Ribas Fürstenau
  • Izabel Cristina Custódio de Souza
  • Marcos Roberto de OliveiraEmail author
Original Article


Methylglyoxal (MG) is a dicarbonyl molecule exhibiting high reactivity and is a major responsible for glycation in human cells. Accumulation of MG is seen in certain diseases, including metabolic disturbances and neurodegeneration. Among other effects, MG promotes mitochondrial dysfunction, leading to bioenergetic decline and redox impairment in virtually any nucleated human cells. The detoxification of MG is dependent on the availability of reduced glutathione (GSH), a major antioxidant that is also utilized in phase II detoxification reactions. The synthesis of GSH is mainly controlled by the transcription factor nuclear factor (erythroid-derived 2)–like 2 (Nrf2). The activation of Nrf2 is stimulated by several reactive compounds, including natural molecules produced by plants. Tanshinone I (T-I) is obtained from Salvia miltiorrhiza Bunge and exerts potent cytoprotective actions in different cell types. Thus, we have investigated here whether and how T-I would be able to protect mitochondria of the human neuroblastoma SH-SY5Y cell line exposed to MG. The cells were pretreated with T-I at 2.5 μM for 2 h before the challenge with MG at 500 μM. T-I significantly attenuated the MG-induced loss of cell viability, bioenergetic decline, and redox impairment in SH-SY5Y cells. The inhibition of the GSH synthesis by buthionine sulfoximine (BSO) at 100 μM suppressed the mitochondrial protection promoted by T-I. The silencing of Nrf2 by small interfering RNA (siRNA) abrogated the synthesis of GSH and the mitochondrial protection stimulated by T-I in SH-SY5Y cells. Therefore, T-I induced mitochondrial protection by a mechanism involving the Nrf2/GSH axis in MG-challenged SH-SY5Y cells.


Tanshinone I Methylglyoxal Mitochondria SH-SY5Y cells Glutathione Nrf2 


Funding Information

MRO receives a “Bolsa de Produtividade em Pesquisa 2 - PQ2” fellow from the Conselho Nacional de Pesquisa e Desenvolvimento Tecnológico (CNPq) (protocol number 301273/2018-9). This research was supported by CNPq (protocol numbers 400216/2016-7 and 460903/2014-4).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12640_2019_91_MOESM1_ESM.pdf (19 kb)
Figure S1 The effects of a pretreatment with tanshinone I (T-I) at 0.5–2.5 μM for 2 h on the viability of SH-SY5Y cells exposed to methylglyoxal (MG) at 500 μM for further 24 h. Data are demonstrated 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 MG-treated cells. (PDF 18 kb)
12640_2019_91_MOESM2_ESM.pdf (86 kb)
Figure S2 T-I alleviates the effects of MG on the mitochondria-related cell death-associated parameters Bcl-2 levels (A), Bax levels (B), cytosolic cytochrome c levels (C), and mitochondrial cytochrome c levels (D) in SH-SY5Y cells. The human neuroblastoma SH-SY5Y cells were administrated with T-I at 2.5 μM for 2 h and then challenged with MG at 500 μM for further 24 h. Data are demonstrated 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 vs MG-treated cells. (PDF 85 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Centro de Ciências Naturais e HumanasUniversidade Federal do ABCSanto AndréBrazil
  2. 2.Programa de Pós-Graduação em Bioquímica e Bioprospecção (PPGBBIO), Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Instituto de BiologiaUniversidade Federal de Pelotas (UFPel)PelotasBrazil
  3. 3.Grupo de Estudos em Neuroquímica e Neurobiologia de Moléculas BioativasUniversidade Federal de Mato Grosso (UFMT)CuiabaBrazil
  4. 4.Programa de Pós-Graduação em Química (PPGQ)Universidade Federal de Mato Grosso (UFMT)CuiabaBrazil
  5. 5.Programa de Pós-Graduação em Ciências da Saúde (PPGCS)Universidade Federal de Mato Grosso (UFMT)CuiabaBrazil

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