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Naringenin Exerts Anti-inflammatory Effects in Paraquat-Treated SH-SY5Y Cells Through a Mechanism Associated with the Nrf2/HO-1 Axis

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Abstract

Naringenin (NGN; 5,7-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one; C15H12O5), a flavanone, is found in citrus fruits and has been viewed as an antioxidant and anti-inflammatory agent. NGN is a potent inducer of the nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulates the expression of heme oxygenase-1 (HO-1), an enzyme exhibiting both antioxidant and anti-inflammatory effects. The complete mechanism by which NGN exerts anti-inflammatory actions is not completely understood yet. Therefore, we investigated here whether NGN would be able to reduce the inflammation induced by paraquat (PQ) in SH-SY5Y cells. Additionally, we analyzed the mechanism associated with the NGN-induced anti-inflammatory effect. We found that a pretreatment with NGN at 80 µM for 2 h decreased the levels of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in PQ-treated SH-SY5Y cells. The production of nitric oxide (NO·) and levels of cyclooxygenase-2 (COX-2) and of the inducible isoform of nitric oxide synthase (iNOS) were downregulated by NGN in the cells exposed to PQ. Moreover, NGN downregulated the activation of the nuclear factor-κB (NF-κB) in PQ-treated cells. The anti-apoptotic and anti-inflammatory effects promoted by NGN were abolished by ZnPP IX (a specific inhibitor of HO-1) or by knockdown of Nrf2 by small interfering RNA (siRNA). Therefore, NGN induced anti-inflammatory effects in PQ-treated SH-SY5Y cells by a mechanism associated with the Nrf2/HO-1 signaling pathway.

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Acknowledgements

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado de Mato Grosso (FAPEMAT).

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Authors and Affiliations

  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), Av. Fernando Corrêa da Costa, 2367, Cuiabá, MT, CEP 78060-900, Brazil

    Marcos Roberto de Oliveira & Cláudia Marlise Balbinotti Andrade

  2. Instituto de Genética e Bioquímica (INGEB), Universidade Federal de Uberlândia (UFU), Patos de Minas, MG, Brazil

    Cristina Ribas Fürstenau

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  1. Marcos Roberto de Oliveira
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  2. Cláudia Marlise Balbinotti Andrade
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  3. Cristina Ribas Fürstenau
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Correspondence to Marcos Roberto de Oliveira.

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11064_2018_2495_MOESM1_ESM.pdf

Figure S1—The effects of NGN treatment on the Nrf2/HO-1 axis. SH-SY5Y cells were treated with NGN at different concentrations for 8 h (a). The effects of a treatment with NGN at 80 µM for different periods on the levels of Nrf2 in the cell nucleus (b). The effects of NGN at different concentrations for 24 h on the content of HO-1 (c). The effects of Nrf2 knockdown (48 h) on the levels of HO-1 in SH-SY5Y cells treated with NGN at 80 µM for 24 h. * p < 0.05 different from the control group; ** p < 0.05 different from the NGN-treated cells transfected with NC siRNA (PDF 100 KB)

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de Oliveira, M.R., Andrade, C.M.B. & Fürstenau, C.R. Naringenin Exerts Anti-inflammatory Effects in Paraquat-Treated SH-SY5Y Cells Through a Mechanism Associated with the Nrf2/HO-1 Axis. Neurochem Res 43, 894–903 (2018). https://doi.org/10.1007/s11064-018-2495-x

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