Kaempferol Attenuates LPS-Induced Striatum Injury in Mice Involving Anti-Neuroinflammation, Maintaining BBB Integrity, and Down-Regulating the HMGB1/TLR4 Pathway

被引:107
作者
Yang, Ying-Lin [1 ,2 ,3 ]
Cheng, Xiao [2 ,3 ]
Li, Wei-Han [2 ,3 ]
Liu, Man [2 ,3 ]
Wang, Yue-Hua [1 ,2 ,3 ]
Du, Guan-Hua [1 ,2 ,3 ]
机构
[1] Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China
[2] Peking Union Med Coll, 2 1, Beijing 100050, Peoples R China
[3] Chinese Acad Med Sci, Inst Mat Med, Beijing Key Lab Drug Target Identificat & New Dru, Beijing 100050, Peoples R China
来源
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 03期
基金
中国国家自然科学基金;
关键词
lipopolysaccharide (LPS); striatum; neuroinflammation; kaempferol; high mobility group box 1 (HMGB1); BLOOD-BRAIN-BARRIER; PARKINSONS-DISEASE; RAT MODEL; MICROGLIAL ACTIVATION; MOUSE MODEL; NEURODEGENERATION; DYSFUNCTION; EXPRESSION; PROTEIN-1; OCCLUDIN;
D O I
10.3390/ijms20030491
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Neuroinflammation has been demonstrated to be linked with Parkinson's disease (PD), Alzheimer's disease, and cerebral ischemia. Our previous investigation had identified that kaempferol (KAE) exerted protective effects on cortex neuron injured by LPS. In this study, the effects and possible mechanism of KAE on striatal dopaminergic neurons induced by LPS in mice were further investigated. The results showed that KAE improved striatal neuron injury, and increased the levels of tyrosine hydroxylase (TH) and postsynaptic density protein 95 (PSD95) in the striatum of mice. In addition, KAE inhibited the production of pro-inflammatory cytokines, including interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF-), reduced the level of monocyte chemotactic protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1), and cyclooxygenase-2 (COX-2) in the striatum tissues. Furthermore, KAE protected blood-brain barrier (BBB) integrity and suppressed the activation of the HMGB1/TLR4 inflammatory pathway induced by LPS in striatum tissues of mice. In conclusion, these results suggest that KAE may have neuroprotective effects against striatum injury that is induced by LPS and the possible mechanisms are involved in anti-neuroinflammation, maintaining BBB integrity, and down-regulating the HMGB1/TLR4 pathway.
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页数:11
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