Biochanin A Regulates Microglia Polarization After SCI by Promoting Autophagy and Blocking the TLR4/NF-κB Pathway

Abstract

Spinal cord injury (SCI) is frequently accompanied by sensorimotor deficits that persist for years in the absence of effective treatments. Biochanin A (BCA), a natural isoflavone, belongs to phytoestrogen. BCA can perform multiple functions, but its role of SCI is unclear. The purpose of this study was to explore the impact and mechanism of BCA on microglia by simulating SCI with lipopolysaccharide (LPS) in vitro. The results showed that BCA inhibited microglial apoptosis and promoted SCI repair by inducing M2 microglia polarization and secretion of anti-inflammatory factors. Notably, the efficacy of the above-mentioned effects of BCA was correlated with autophagic flux. We further explored the underlying molecular mechanisms and confirmed the critical importance of toll-like receptor 4 (TLR4) in counteracting the effect of BCA on LPS-BV-2 cells. The TLR4/NF-κB pathway was shown to promote M1 microglial polarization, inflammation and cellular apoptosis. In conclusion, BCA blocks the TLR4/NF-κB pathway to inhibit M1 microglial polarization and apoptosis after SCI. This study is expected to provide the scientific basis for the SCI.