Open Access7‐methoxyflavanone alleviates neuroinflammation in lipopolysaccharide‐stimulated microglial cells by inhibiting TLR4/MyD88/MAPK signalling and activating the Nrf2/NQO‐1 pathway
Author(s) -
Qu Zhao,
Chen Yan,
Luo ZhuoHui,
Shen XiaoLing,
Hu YingJie
Publication year - 2020
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13219
Subject(s) - neuroinflammation , mapk/erk pathway , neuroprotection , microglia , chemistry , tlr4 , microbiology and biotechnology , nitric oxide synthase , kinase , signal transduction , p38 mitogen activated protein kinases , tumor necrosis factor alpha , nitric oxide , biology , inflammation , pharmacology , endocrinology , immunology , organic chemistry
Objectives Neuroprotective potential of 7‐methoxyflavanone (7MF) and its underlying mechanism was investigated. Methods Inhibitory effects of 7MF on microglial activation and neuroinflammation were evaluated by employment of lipopolysaccharide (LPS)‐induced BV2 microglial cells. Changes in expression of genes and proteins of interest were investigated by RT‐qPCR analysis and Western blot analysis. Inhibitory effects of 7MF on microglial overactivation were verified in LPS‐treated C57BL/6J mice using ionized calcium‐binding adaptor molecule‐1 (Iba1) in the brain and interleukin‐6 (IL‐6) in serum as indicators. Key findings In BV2 cells, pretreatment with 7MF antagonized LPS‐induced production of inflammatory factors IL‐6, tumour necrosis factor‐α (TNF‐α), cyclooxygenase‐2 (COX‐2), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule‐1 (ICAM‐1) and monocyte chemoattractant protein‐1 (MCP‐1). Mechanistic studies revealed reduced expression of Toll‐like receptor 4 (TLR4), myeloid differentiation factor‐88 (MyD88), phosphorylated forms of c‐Jun N‐terminal kinase (p‐JNK) and extracellular signal‐regulated kinases 1/2 (p‐ERK) but increased nuclear accumulation of nuclear factor erythroid 2‐related factor 2 (Nrf2) and cellular expression of NAD(P)H quinone dehydrogenase‐1 (NQO‐1) by 7MF. In LPS‐treated mice, pretreatment with 7MF reduced the brain level of Iba1 and serum level of IL‐6. Conclusions 7‐methoxyflavanone inhibited LPS‐stimulated TLR4/MyD88/MAPK signalling and activated Nrf2‐mediated transcription of antioxidant protein NQO‐1, showing antineuroinflammatory effect, so it is a potential neuroprotective agent.