Complanatuside A improves functional recovery after spinal cord injury through inhibiting JNK signaling-mediated microglial activation

Abstract

Background and aimsComplanatuside A (ComA) is a flavonoid-rich compound in Astragalus membranaceus that has anti-inflammatory and neuroprotective effects. In this study, we focused on the effect of ComA on spinal cord injury (SCI) in mice and explored its possible mechanisms. MethodsThe SCI model was constructed using C57BL/6J mice, and the effect of ComA on motor function recovery in SCI mice was evaluated through the BMS (Basso Mouse Scale) and footprint test. The histological effects of ComA on SCI mice were evaluated by hematoxylin-eosin (H&E) staining, Luxol-fast blue (LFB) staining, and Nissl staining. In both in vivo and in vitro experiments, we detected the activation of microglia and the release of inflammatory factors through molecular experiments. Immunofluorescence and Western blotting confirmed that ComA can prevent neuronal apoptosis caused by activated microglia through the c-Jun N-terminal kinase (JNK) pathway. ResultsOur research results confirm that ComA can improve motor function in mice after SCI. Our in vitro results indicate that ComA can inhibit the activation of BV2 cells and the release of proinflammatory mediators. In addition, ComA can prevent neuronal cell apoptosis caused by activated BV2 cells. Finally, we found that ComA works through the JNK signaling pathway. ConclusionsComA can accelerate the restoration of motor function in mice after SCI, possibly by reducing neuronal apoptosis via inhibition of JNK-related signaling pathways, a reduction in microglial activation, and inhibition of inflammatory factor release. Our data indicate that ComA is a promising drug candidate for improving functional recovery in patients with SCI.