Forsythoside B attenuates neuro-inflammation and neuronal apoptosis by inhibition of NF-κB and p38-MAPK signaling pathways through activating Nrf2 post spinal cord injury.

Background: Spinal cord injury (SCI) is a ruinous neurological pathology that results in locomotor and sensory impairment. Neuro-inflammation and secondary neuronal apoptosis contribute to SCI, with anti-inflammatory therapies the focus of many SCI studies. Forsythoside B (FTS•B), a phenylethanoid glycoside extracted from the leaves of Lamiophlomis rotata Kudo, has been shown previously to have anti-inflammatory properties. Nevertheless, the therapeutic effect of FTS•B on neuro-inflammation after SCI is unknown.

Methods: Neuro-inflammation was assessed by western blotting (WB), immunofluorescence (IF) staining, and enzyme-linked immunosorbent assay (ELISA) both in vitro and in vivo. Secondary neuronal apoptosis was simulated in a microglia-neuron co-culture model with the degree of apoptosis measured by WB, IF, and TUNEL staining. In vivo, FTS•B (10 mg/kg, 40 mg/kg) were intraperitoneally injected into SCI mice. Morphological changes following SCI were evaluated by Nissl, Hematoxylin-eosin, and Luxol Fast Blue staining. Basso Mouse Scale scores were used to evaluate locomotor function recovery.

Results: FTS•B markedly decreased the levels of iNOS, COX-2 and signature mediators of inflammation. Phosphorylated p38 and nuclear factor-kappa B (NF-κB) were markedly decreased by FTS•B. Additionally, FTS•B-induced inhibition of NF-κB and p38-MAPK signaling pathways was reversed by Nrf2 downregulation. Administration of FTS•B also significantly reduced apoptosis-related protein levels indicating that FTS•B ameliorated secondary neuronal apoptosis. FTS•B administration inhibited glial scar formation, decreased neuronal death, tissue deficiency, alleviated demyelination, and promoted locomotor recovery.

Conclusion: FTS•B effectively attenuates neuro-inflammation and secondary neuronal apoptosis by inhibition of NF-κB and p38-MAPK signaling pathways through activating Nrf2 after SCI. This study demonstrates FTS•B to be a potential therapeutic for SCI.