2-cyclohexylamino-5,8-dimethoxy-1,4-naphthoquinone inhibits LPS-induced BV2 microglial activation through MAPK/NF-kB signaling pathways

• Main Authors: Hu-Nan Sun, Gui-Nan Shen, Yong-Zhe Jin, Yu Jin, Ying-Hao Han, Li Feng, Lei Liu, Mei-Hua Jin, Ying-Hua Luo, Tea-Ho Kwon, Yu-Dong Cui, Cheng-Hao Jin
• Format: Article
• Language: English
• Published: Elsevier 2016-07-01
• Series: Heliyon
• Subjects: Neuroscience; Immunology; Cell biology; Medicine; Biochemistry
• Online Access: http://www.sciencedirect.com/science/article/pii/S2405844016301657

Aims: To verify the effects of several 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) derivatives on LPS-induced NO production, cellular ROS levels and cytokine expression in BV-2 microglial cells. Main methods: An MTT assay and FACS flow cytometry were performed to assess the cellular viability and apoptosis and cellular ROS levels, respectively. To examine the expression of pro-inflammatory cytokines and cellular signaling pathways, semi-quantitative RT-PCR and Western blotting were also used in this study. Key findings: Among the six newly synthesized DMNQ derivatives, 2-cyclohexylamino-5,8-dimethoxy-1,4-naphthoquinone (R6) significantly inhibited the NO production, cellular ROS levels and the cytokines expression in BV-2 microglial cells, which stimulated by LPS. Signaling study showed that compound R6 treatment also significantly down-regulated the LPS-induced phosphorylation of MAPKs (ERK, JNK and p38) and decreased the degradation of IκB-α in BV2 microglial cells. Significance: Our findings demonstrate that our newly synthesized compound derived from DMNQ, 2-cyclohexylamino-5,8-dimethoxy-1,4-naphthoquinone (R6), might be a therapeutic agent for the treatment of glia-mediated neuroinflammatory diseases.