Tangeretin alleviates inflammation and oxidative response induced by spinal cord injury by activating the Sesn2/Keap1/Nrf2 pathway

Spinal cord injury (SCI) is a severe disabling disease that is characterized by inflammation and oxidative reactions. Tangeretin has been shown to possess significant antioxidant and anti-inflammatory activities. The Keap1/Nrf2 pathway, downstream of the Sesn2 gene, is involved in regulating the inflammation and oxidative response. The main objective of this study was to investigate the effect of tangeretin on SCI and its possible mechanism through cell and animal models. A T9 clamp injury was used for the mouse model and the LPS-induced stimulation of BV-2 cells was used for the cell model. The improvement of motor function after SCI was assessed by open field, swimming, and footprint experiments. The morphological characteristics of mouse spinal cord tissue and the levels of INOS, Sesn2, TNF-α, Keap1, Nrf2, IL-10, and reactive oxygen species (ROS) in vivo and in vitro were measured by several methods including western blotting, qPCR, immunofluorescence, HE, and Nissl staining. In vivo data showed that tangeretin can improve motor function recovery and reduce neuron loss and injury size in mice with SCI. Simultaneously, the in vitro findings suggested that treatment of BV-2 cells with tangeretin after LPS stimulation reduced the production of inflammatory factors and ROS, and could convert BV-2 cells from the M1 to the M2 type. Furthermore, Sesn2 knockout suppressed Keap1/Nrf2, inflammatory factors, ROS levels, and the M1 to M2 transition. Tangeretin can alleviate the inflammation and oxidative response induced by SCI by activating the Sesn2/Keap1/Nrf2 pathway.