Journal
PHYTOMEDICINE
Volume 43, Issue -, Pages 11-20Publisher
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.phymed.2018.03.039
Keywords
Genistein; Microglia; G protein-coupled estrogen receptor; Lipopolysaccharide; Neuroinflammation
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Funding
- National Natural Science Foundation of China [31271150, 81430024]
- Taishan Scholarship
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Background: Genistein (GEN), a phytoestrogen that is extracted from leguminous plants, can bind to estrogen receptor and exert biological effects. G protein-coupled estrogen receptor (GPER), a novel membrane estrogen receptor, has been reported to be involved in the anti-inflammatory process. In the present study, using BV2 microglial cell line and primary microglial culture, we evaluated the involvement of GPER in the anti-inflammatory effects of genistein against lipopolysaccharide (LPS)-induced microglia activation. Methods: The anti-inflammatory effects of genistein were investigated in LPS-induced microglial activation in murine BV2 microglial cell line and primary microglial culture. Anti-inflammatory properties of genistein were determined by MTT, real time PCR, ELISA and western blot analysis. The pharmacological blockade and lentivirus-mediated siRNA knockdown of GPER were used to study the underlying mechanism. Results: The results showed that genistein exerted inhibitory effects on LPS-induced expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6). Pre-treatment with GPER antagonist G15 could significantly block the anti-inflammatory effects of genistein. Moreover, the inhibitory effects of genistein on LPS-induced activation of MAPKs and NF-kappa B signaling pathways could also be blocked by G15. Lentivirus-mediated siRNA knockdown of GPER significantly inhibited the anti-inflammatory effects of genistein in BV2 cells. Further study revealed that genistein treatment could increase the gene and protein expressions of GPER in BV2 cells. Conclusion: Taken together, these data provide the first evidence that genistein exerts anti-inflammatory effects in microglial cells via GPER activation. These beneficial effects of genistein may represent a new strategy for the treatment of neuroinflammatory diseases.
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