期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 56, 期 -, 页码 29-35出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2018.01.002
关键词
Kaempferol; Lipopolysaccharide (LPS); Blood-brain barrier (BBB); Toll-like receptor-4 (TLR4); Myeloid differentiation factor 88 (MyD88); High-mobility group protein 1 (HMGB1)
资金
- National Natural Science Foundation of China [81473383]
- Medical and Health Innovation Project of Chinese Academy of Medical Sciences [2016-I2M-3-007]
- Significant New-Drugs Creation of Science and Technology Major Projects [2017ZX09101003-003-019]
- Innovation Fund for Graduate of Beijing Union Medical College [2017-1007-02]
Kaempferol is a natural flavonoid with many biological activities including anti-oxidation and anti-inflammation. Nevertheless, its anti-neuroinflammation role and the relevant mechanism remain unclear. The present study was to investigate effects of kaempferol against LPS-induced neuroinflammation and blood-brain barrier dysfunction as well as the mechanism in mice. BALB/c mice were treated with LPS 5 mg/kg to induce inflammation after pre-treatment with kaempferol 25, 50, or 100 mg/kg for 7 days. The results showed that kaempferol reduced the production of various pro-inflammatory factors and inflammatory proteins including IL-1 beta, IL-6, TNF-alpha, MCP-1, COX-2 and iNOS in brain tissues. In addition, kaempferol also protected BBB integrity and increased BBB related proteins including occludin-1, claudin-1 and CX43 in brain of LPS-induced mice. Furthermore, kaempferol significantly reduced HMGB1 level and suppressed TLR4/MyD88 inflammatory pathway in both transcription level and translation level. These results collectively suggested that kaempferol might be a promising neuroprotective agent for alleviating inflammatory responses and BBB dysfunction by inhibiting HMGB1 release and down-regulating TLR4/MyD88 inflammatory pathway.
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