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

• Published in: Molecular neurobiology Vol. 55; no. 1; pp. 890 - 897
• Main Authors: de Oliveira, Marcos Roberto, de Souza, Izabel Cristina Custódio, Fürstenau, Cristina Ribas
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2018; Springer Nature B.V
• Subjects: Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Antioxidants; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Line, Tumor; Cell Survival - drug effects; Cyclooxygenase-2; Cytokines - metabolism; Detoxification; Diterpenes, Abietane - pharmacology; Down-Regulation - drug effects; Gene Knockdown Techniques; Heme; Heme oxygenase (decyclizing); Heme Oxygenase-1 - metabolism; Humans; IL-1β; Inflammation; Neurobiology; Neurology; Neurosciences; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; NF-κB protein; Nitric Oxide - metabolism; Oxygenase; Paraquat; Paraquat - toxicity; Phenols; Signal transduction; Signal Transduction - drug effects; siRNA; Transcription factors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Antioxidant; Nuclear factor-κB; Nrf2; Anti-inflammatory; Carnosic acid; Heme oxygenase-1
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-017-0389-6

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.