title: Carnosic Acid Induces Anti-Inflammatory Effects in Paraquat-Treated SH-SY5Y Cells Through a Mechanism Involving a Crosstalk Between the Nrf2/HO-1 Axis and NF-κB.
abstract: Carnosic acid (CA) is a phenolic diterpene obtained from Rosmarinus officinalis L. and has demonstrated cytoprotective properties in several experimental models. CA exerts antioxidant effects by upregulating the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which controls the expression of antioxidant and phase II detoxification enzymes. Heme oxygenase-1 (HO-1) expression is modulated by Nrf2 and has been demonstrated as part of the mechanism underlying the CA-induced cytoprotection. Nonetheless, it remains to be studied whether and how HO-1 would mediate CA-elicited anti-inflammatory effects. Therefore, we have investigated here whether and how CA would prevent paraquat (PQ)-induced inflammation-related alterations in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were pretreated for 12 h with CA at 1 μM before exposure to PQ for further 24 h. CA suppressed the PQ-induced alterations on the levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) through a mechanism involving the activation of the Nrf2/HO-1 axis. Furthermore, we observed a crosstalk between the Nrf2/HO-1 signaling pathway and the activation of the nuclear factor-κB (NF-κB) transcription factor, since administration of ZnPP IX (specific inhibitor of HO-1) or Nrf2 knockdown using small interfering RNA (siRNA) abolished the anti-inflammatory effects induced by CA. Moreover, administration of SN50 (specific inhibitor of NF-κB) inhibited the PQ-induced inflammation-related effects in SH-SY5Y cells. Therefore, CA exerted anti-inflammatory effects in SH-SY5Y cells through an Nrf2/HO-1 axis-dependent manner associated with downregulation of NF-κB.
authors.affiliation: 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, CEP 78060-900, Cuiabá, MT, Brazil. mrobioq@gmail.com.
authors.forename: Marcos Roberto
authors.initials: MR
authors.lastname: de Oliveira
authors.affiliation: Programa de Pós-Graduação em Bioquímica e Bioprospecção (PPGBBIO), Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Instituto de Biologia, Universidade Federal de Pelotas (UFPel), Pelotas, RS, Brazil.
authors.forename: Izabel Cristina Custódio
authors.initials: ICC
authors.lastname: de Souza
authors.affiliation: Instituto de Genética e Bioquímica (INGEB), Universidade Federal de Uberlândia (UFU), Patos de Minas, MG, Brazil.
authors.forename: Cristina Ribas
authors.initials: CR
authors.lastname: Fürstenau
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D045784:Abietanes; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D009569:Nitric Oxide; D051547:Heme Oxygenase-1; C018381:salvin; D010269:Paraquat
keywords: Anti-inflammatory; Antioxidant; Carnosic acid; Heme oxygenase-1; Nrf2; Nuclear factor-κB