Anti-inflammatory effect of oleuropein on microglia through regulation of Drp1-dependent mitochondrial fission

• Published in: Journal of neuroimmunology Vol. 306; pp. 46 - 52
• Main Authors: Park, Junghyung, Min, Ju-Sik, Chae, Unbin, Lee, Joon Yeop, Song, Kyung-Sik, Lee, Hyun-Shik, Lee, Hong Jun, Lee, Sang-Rae, Lee, Dong-Seok
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.05.2017
• Subjects: Allergy and Immunology; Animals; Anti-Inflammatory Agents - pharmacology; Cell Line, Transformed; Cytokines - metabolism; Dose-Response Relationship, Drug; Drp1; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Inflammation; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Iridoids - pharmacology; Lipopolysaccharides - pharmacology; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - genetics; Mice; Microglia; Microglia - drug effects; Mitochondria - drug effects; Mitochondrial dynamics; Mitochondrial Dynamics - drug effects; Mitochondrial Dynamics - genetics; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurology; Nitric Oxide - metabolism; Oleuropein; Reactive Oxygen Species - metabolism; RNA, Messenger - metabolism; ROS; Transduction, Genetic; NO; nitric oxide; Mitochondrial dynamics; cyclooxygenase-2; dynamin-related protein 1; Inflammation; MAPK; LPS; Drp1; inducible nitric oxide synthase; Microglia; mitogen-activated protein kinase; NF-κB; Cox-2; Oleuropein; NADPH oxidase; ROS; reactive oxygen species; iNOS; lipopolysaccharide; GAPDH; nicotinamide adenine dinucleotide phosphate oxidase; nuclear factor kappa-light-chain-enhancer of activated B cells; glyceraldehyde 3-phosphate dehydrogenase
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2017.02.019

Abstract Oleuropein is a primary phenolic compound found in olive leaf and Fraxinus rhynchophylla . Here, we investigated the impact of oleuropein on LPS-induced BV-2 microglial cells. Oleuropein suppressed the LPS-induced increase in pro-inflammatory mediators, such as nitric oxide, and pro-inflammatory cytokines, via inhibition of ERK/p38/NF-κB activation and reactive oxygen species (ROS) generation. Furthermore, it suppressed LPS-induced excessive mitochondrial fission, which regulates mitochondrial ROS generation and pro-inflammatory response by diminishing Drp1 dephosphorylation. Collectively, we demonstrated that oleuropein suppresses pro-inflammatory response of microglia by inhibiting Drp1-dependent mitochondrial fission. Our findings suggest a potential role of oleuropein in microglial inflammation-mediated neurodegenerative disorders.