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Neurochem Res. 2018 Apr;43(4):894-903. doi: 10.1007/s11064-018-2495-x. Epub 2018 Feb 6.

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

Author information

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. mrobioq@gmail.com.
2
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.
3
Instituto de Genética e Bioquímica (INGEB), Universidade Federal de Uberlândia (UFU), Patos de Minas, MG, Brazil.

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.

KEYWORDS:

Anti-inflammatory; Heme oxygenase-1; Naringenin; Nrf2; Nuclear factor-κB

PMID:
29411263
DOI:
10.1007/s11064-018-2495-x
[Indexed for MEDLINE]

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