Oleuropein Suppresses LPS-Induced Inflammatory Responses in RAW 264.7 Cell and Zebrafish

• Published in: Journal of agricultural and food chemistry 2015-02, Vol.63 (7), p.2098-2105
• Main Authors: Ryu, Su-Jung, Choi, Hyeon-Son, Yoon, Kye-Yoon, Lee, Ok-Hwan, Kim, Kui-Jin, Lee, Boo-Yong
• Format: Article
• Language: English
• Subjects: Animals; anti-inflammatory activity; anti-inflammatory agents; Anti-Inflammatory Agents - administration & dosage; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - immunology; Danio rerio; enzyme immunoassays; genes; inducible nitric oxide synthase; inflammation; Inflammation - drug therapy; Inflammation - genetics; Inflammation - immunology; interleukin-1beta; interleukin-6; Interleukin-6 - genetics; Interleukin-6 - immunology; Iridoids - administration & dosage; leaves; lipopolysaccharides; Lipopolysaccharides - adverse effects; Lipopolysaccharides - immunology; macrophages; Macrophages - drug effects; Macrophages - immunology; Mice; mitogen-activated protein kinase; NF-kappa B - genetics; NF-kappa B - immunology; nitric oxide; Olea - chemistry; oleuropein; olives; phenolic compounds; phosphorylation; Plant Extracts - administration & dosage; Plant Leaves - chemistry; prostaglandin synthase; Zebrafish
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf505894b

Oleuropein is one of the primary phenolic compounds present in olive leaf. In this study, the anti-inflammatory effect of oleuropein was investigated using lipopolysaccharide (LPS)-stimulated RAW 264.7 and a zebrafish model. The inhibitory effect of oleuropein on LPS-induced NO production in macrophages was supported by the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, our enzyme immunoassay showed that oleuropein suppressed the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-6 (IL-6). Oleuropein inhibited the translocation of p65 by suppressing phosphorylation of inhibitory kappa B-α (IκB-α). Oleuropein also decreased activation of ERK1/2 and JNK, which are associated with LPS-induced inflammation, and its downstream gene of AP-1. Furthermore, oleuropein inhibited LPS-stimulated NO generation in a zebrafish model. Taken together, our results demonstrated that oleuropein could reduce inflammatory responses by inhibiting TLR and MAPK signaling, and may be used as an anti-inflammatory agent.