Sinomenine Attenuates Traumatic Spinal Cord Injury by Suppressing Oxidative Stress and Inflammation via Nrf2 Pathway

Abstract

Traumatic spinal cord injury (SCI) is a devastating condition with few efficacious drugs. Sinomenine, a bioactive alkaloid extracted from medicinal herb, has been used as a treatment of rheumatoid diseases. This present study explored the therapeutic effects of sinomenine on locomotor dysfunction and neuropathology in SCI. Our findings revealed that sinomenine mitigated neurological deficits and enhanced neuronal preservation, paralleled with a reduction of apoptosis. Also, sinomenine significantly reduced inflammatory cytokines and oxidative stress factors. We further examined erythroid-2-related factor 2 (Nrf2) nuclear translocation, which mainly controls the coordinated expression of important antioxidant and detoxification genes. An increase in Nrf2 translocation from cytoplasm to nucleus and Nrf2-mediated transactivation was observed after sinomenine administration. Knocking down Nrf2 by siRNA could counteract sinomenine-mediated anti-oxidant stress and anti-inflammation following H₂O₂-stimulated and LPS-stimulated PC12 cells. Together, our findings indicated that sinomenine has the potential to be an effective therapeutic agent for SCI by inhibiting inflammation and oxidative stress via Nrf2 activation.

Keywords: Inflammation; Nrf2; Oxidative stress; Sinomenine; Spinal cord injury.