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.

Pramipexole has a neuroprotective effect in spinal cord injury and upregulates D2 receptor expression in the injured spinal cord tissue in rats.

Spinal cord injury (SCI) has emerged as a prevalent condition with limited effective treatment options. The neuroprotective role of pramipexole (PPX) in inhibiting nerve cell apoptosis in central nervous system injuries is well established. Therefore, we investigated the effects of PPX in SCI. Adult Sprague-Dawley rats were divided into four groups (sham, SCI, PPX-0.25, and PPX-2.0 groups) according to the PPX therapy (n = 24). Then, SCI was induced using the modified Allen method, and PPX was intravenously administered into the tail at dosages of 0.25 or 2.0 mg/kg following the injury. Motor function was evaluated using the Rivlin-modified inclined plate apparatus and the Basso Beattie Bresnahan (BBB) workout scale. Western blotting assay was used to measure protein expression levels of DRD2, NeuN, Bax/Bcl-2, and caspase-3. Furthermore, immunohistochemistry assessed the effect of PPX on the quantity of NeuN-positive cells in the spinal cord tissue after SCI. Our findings revealed that the BBB and slanting board test scores of the PPX-treated model groups were considerably higher for the SCI group and significantly lower for the sham operation group (P < 0.001). Moreover, the PPX-2.0 group exhibited significantly higher NeuN expression levels than the SCI group (P < 0.01). Our findings indicate that PPX exerts a neuroprotective effect in secondary neuronal injury following SCI, facilitating the recovery of hind limb function by downregulating Bax/Bcl-2, caspase-3, and IL-1ß.