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

Junghyung Park; Ju-Sik Min; Unbin Chae; Joon Yeop Lee; Kyung-Sik Song; Hyun-Shik Lee; Hong Jun Lee; Sang-Rae Lee; Dong-Seok Lee

doi:10.1016/j.jneuroim.2017.02.019

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

J Neuroimmunol. 2017 May 15:306:46-52. doi: 10.1016/j.jneuroim.2017.02.019. Epub 2017 Mar 1.

Authors

Junghyung Park¹, Ju-Sik Min², Unbin Chae¹, Joon Yeop Lee³, Kyung-Sik Song⁴, Hyun-Shik Lee¹, Hong Jun Lee⁵, Sang-Rae Lee⁶, Dong-Seok Lee⁷

Affiliations

¹ School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea; College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
² School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea; College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea; Rare Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
³ Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea; Traditional Korean Medicine Technology Division, National Development Institute of Korean Medicine, Gyeongsangbuk-do, Republic of Korea.
⁴ Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea.
⁵ Biomedical Research Institute, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
⁶ National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do, Republic of Korea.
⁷ School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea; College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea. Electronic address: lee1@knu.ac.kr.

PMID: 28385187
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.

Keywords: Drp1; Inflammation; Microglia; Mitochondrial dynamics; Oleuropein; ROS.

MeSH terms

Animals
Anti-Inflammatory Agents / pharmacology*
Cell Line, Transformed
Cytokines / metabolism
Dose-Response Relationship, Drug
Gene Expression Regulation / drug effects
Gene Expression Regulation / genetics
Intercellular Signaling Peptides and Proteins / genetics
Intercellular Signaling Peptides and Proteins / metabolism*
Iridoid Glucosides
Iridoids / pharmacology*
Lipopolysaccharides / pharmacology
Luminescent Proteins / genetics
Luminescent Proteins / metabolism
MAP Kinase Signaling System / drug effects
MAP Kinase Signaling System / genetics
Mice
Microglia / drug effects*
Mitochondria / drug effects*
Mitochondrial Dynamics / drug effects*
Mitochondrial Dynamics / genetics
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Nitric Oxide / metabolism
RNA, Messenger / metabolism
Reactive Oxygen Species / metabolism
Transduction, Genetic

Substances

Anti-Inflammatory Agents
Cytokines
Intercellular Signaling Peptides and Proteins
Iridoid Glucosides
Iridoids
Lipopolysaccharides
Luminescent Proteins
Nerve Tissue Proteins
RNA, Messenger
Reactive Oxygen Species
collapsin response mediator protein-2
fluorescent protein 583
oleuropein
Nitric Oxide