Zhenbao Pill Attenuates Microglia Activation to Improve Spinal Cord Injury via miR-214-5p/SOX4/β-catenin Axis

Zhenbao pill (ZBP) has been shown to improve outcomes in spinal cord injury (SCI). However, its potential regulatory mechanisms in SCI remain to be elucidated. This study aimed to define the role of ZBP and its underlying molecular mechanisms in SCI, both in vitro and in vivo. Our findings indicated that ZBP ameliorated SCI by inhibiting neuronal apoptosis and the inflammatory response through the enhancement of miR-214-5p in vivo. In vitro, ZBP significantly reduced the levels of inflammatory factors, increased cell viability, and decreased apoptosis induced by oxygen-glucose deprivation (OGD)-activated microglia via miR-214-5p. Furthermore, the addition of miR-214-5p diminished the inflammatory response, enhanced cell viability, and suppressed apoptosis in OGD-treated microglia. We identified SRY-box transcription factor 4 (SOX4) as a potential target of miR-214-5p. Overexpression of SOX4 negated the effects of miR-214-5p on the inflammatory response, cell viability, and apoptosis in OGD-activated microglia. ZBP inhibited SOX4/β-catenin activation and reduced pro-inflammatory cytokine secretion by enhancing miR-214-5p in activated microglia. In summary, our findings demonstrate that ZBP mitigates SCI by inhibiting neuronal damage caused by activated microglia through the miR-214-5p/SOX4/β-catenin axis, providing valuable insights into the molecular basis of ZBP as a therapeutic agent for SCI.