Anti-neuroinflammatory effects of citreohybridonol involving TLR4-MyD88-mediated inhibition of NF-kappa B and MAPK signaling pathways in lipopolysaccharide-stimulated BV2 cells

作者：Cho Kwang Ho; Kim Dong Cheol; Yoon Chi Su; Ko Won Min; Lee Seung Jun; Sohn Jae Hak; Jang Jae Hyuk; Ahn Jong Seog; Kim Youn Chul^*; Oh Hyuncheol^*

来源：Neurochemistry International, 2016, 95: 55-62.

DOI：10.1016/j.neuint.2015.12.010

• Anti-neuroinflammation
• Citreohybridonol
• Marine-derived fungus
• Mitogen-activated protein kinase (MAPK)
• Nuclear factor-kappa B (NF-kappa B)

In the course of searching for anti-neuroinflammatory metabolites from marine fungi, citreohybridonol was isolated from marine-derived fungal strain Toxicocladosporium sp. SF-5699. Citreohybridonol inhibited production of nitric oxide (NO) and prostaglandin E-2 (PGE(2)) in BV2 cells stimulated by lipopolysaccharide (LPS). Citreohybridonol also suppressed the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and other pro-inflammatory cytokines including interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in the LPS-stimulated cells. In the further study, citreohybridonol disturbed nuclear translocation of nuclear factor-kappa B (NF-kappa B) in LPS-stimulated BV2 cells by inhibiting the phosphorylation of the inhibitor kappa B-alpha (I kappa B-alpha). Citreohybridonol also had inhibitory effect on the LPS-stimulated phosphorylation of p38 mitogen-activated protein kinase (MAPK). Finally, citreohybridonol suppressed the protein expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) in LPS-induced BV2 cells. These results suggest that citreohybridonol has anti-neuroinflammatory effect in LPS-stimulated BV2 cells by modulating TLR4-mediated several inflammatory pathways such as NF-kappa B and p38 MAPK pathways.

• 出版日期2016-5