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

Abstract

BackgroundSpinal 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. MethodsNeuro-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. ResultsFTS•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. ConclusionFTS•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.