Loganin reduces neuroinflammation and promotes functional recovery after spinal cord injury through inhibiting NF-κB/NLRP3 signalling

The highly disabling nature of spinal cord injuries (SCI) and high cost of treatment and rehabilitation impose a burden on families and society. Loganin has potential medicinal value in alleviating neuroinflammation. This study aimed to explore whether loganin can be used to reduce SCI-induced neuroinflammation and elucidate the molecular mechanisms underlying its action. An SCI rat model was developed to assess whether loganin promotes motor recovery after SCI. The anti-inflammatory effects of loganin on the dorsal horn of the spinal cord were identified by haematoxylin-eosin and immunohistochemical staining. The inflammatory effects of loganin were characterised using a lipopolysaccharide (LPS)-induced neuroinflammatory model in BV2 cells. For mechanistic exploration, the signalling pathways and target proteins of loganin action were predicted using bioinformatics and computational biology and then validated in cellular inflammation models. Loganin promoted animal motor recovery after SCI at the behavioural level, and it inhibited M1 differentiation of microglia and reduced NOD-like receptor thermal protein domain associated protein 3 (NLRP3)-mediated inflammatory responses at the tissue level. Loganin inhibited LPS-induced inflammation in BV2 cells, and bioinformatics and computational biology suggested that loganin acts on the p65 protein through the nuclear factor kappa-B (NF-κB)/NLRP3 signalling pathway. This was validated in a cellular model in which p65 trans-overexpression eliminated the downregulation of inflammatory factors by loganin. In conclusion, loganin reduces neuroinflammatory responses and promotes motor recovery after SCI. Loganin inhibits the NF-κB/NLRP3 signalling pathway by targeting the p65 protein to achieve repair.