Formononetin inhibits neuroinflammation and increases estrogen receptor beta (ERβ) protein expression in BV2 microglia

被引:58
作者
El-Bakoush, Abdelmeniem [1 ]
Olajide, Olumayokun A. [1 ]
机构
[1] Univ Huddersfield, Sch Appl Sci, Dept Pharm, Huddersfield HD1 3DH, W Yorkshire, England
关键词
Formononetin; Neuroinflanunation; NF-kappa B; ER beta; NF-KAPPA-B; HUMAN BREAST-CANCER; TRIFOLIUM-PRATENSE; ALZHEIMERS-DISEASE; ASTRAGALUS-MEMBRANACEUS; DOPAMINERGIC-NEURONS; PARKINSONS-DISEASE; INDUCED APOPTOSIS; IN-VITRO; CELLS;
D O I
10.1016/j.intimp.2018.06.016
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Formononetin is a bioactive non-steroidal polyphenol found in a variety of plants. In this study we evaluated the effects of formononetin on neuroinflammation in LPS-stimulated BV2 microglia. Results showed that formononetin significantly reduced the production of TNF-alpha, IL-6 and IL-1 beta, nitrite and PGE(2), as well as protein levels of iNOS and COX-2. Reporter gene assays showed that formononetin produced inhibition of NF-kappa B luciferase activity in HEK293 cells stimulated with TNF-alpha. Immunoblotting experiments revealed an inhibition of IKK alpha phosphorylation, with the resultant attenuation of phosphorylation and degradation of I kappa B alpha following LPS stimulation. Formononetin also produced an inhibition of nuclear translocation and DNA binding by NF-kappa B following LPS stimulation. RNAi experiments showed that transfection of BV2 microglia with ERP siRNA resulted in the loss of anti-inflammatory action of formononetin. MTT assay and MAP2 immunoreactivity experiments showed that formononetin produced significant neuroprotective activity by preventing BV2 microglia conditioned media-induced toxicity to HT22 neurons. Investigations on the effect of formononetin on MCF7 breast cancer cells revealed that, while the compound significantly increased ER-luciferase activity, its effects on proliferation were modest. This study has established that formononetin inhibits neuroinflammation by targeting NF-kappa beta signalling pathway in BV2 microglia, possibly through mechanisms involving ER beta. Formononetin appears to modulate ER beta in MCF7 breast cancer cells with limited proliferative effect. Formononetin could therefore serve as a chemical scaffold for the development of novel compounds which have selective neuroprotective actions in the brain.
引用
收藏
页码:325 / 337
页数:13
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