期刊
NEUROCHEMICAL RESEARCH
卷 43, 期 4, 页码 894-903出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-018-2495-x
关键词
Naringenin; Anti-inflammatory; Nrf2; Heme oxygenase-1; Nuclear factor-kappa B
资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Fundacao de Amparo a Pesquisa do Estado de Mato Grosso (FAPEMAT)
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 A mu M for 2 h decreased the levels of pro-inflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in PQ-treated SH-SY5Y cells. The production of nitric oxide (NO center dot) 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-kappa B (NF-kappa B) 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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