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

Highlight•Oleuropein inhibited the LPS-induced production of pro-inflammatory mediators.•Oleuropein prevented the LPS-induced ERK, p38, and NF-κB activation.•Oleuropein diminished LPS-induced ROS generation.•Oleuropein suppressed LPS-induced excessive mitochondrial fission.

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.

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