Piperine Attenuates the Inflammatory Response, Oxidative Stress and Pyroptosis to Facilitate Recovery After Spinal Cord Injury via Autophagy Enhancement

Abstract Background: Spinal cord injury (SCI) is a serious injury that can lead to irreversible motor dysfunction and subsequently result in disability and even death. Due to its complicated pathogenic mechanism, there are no effective drug treatments. Piperine, a natural active alkaloid extracted from black pepper, suppressed inflammation in a previous study. The aim of this study was to investigate the therapeutic effect of piperine in a spinal cord injury model.Methods: Spinal cord injury was induced in C57BL/6 mice by clamping the spinal cord with a vascular clip (15 g force; Oscar) for 1 min. Eighty mice were divided randomly into the following four groups: The Sham group (n = 20), the SCI+Vehicle group (n = 20), the SCI+ Piperine group (n = 20), and the SCI+ Piperine+3MA group (n = 20). Before SCI and every 2 days post-SCI, evaluations of the Basso mouse scale (BMS) were performed. On day 14 after SCI, inclined plane tests and footprint analyses were performed. On postoperative day 3, the spinal cord was harvested to assess pyroptosis, reactive oxygen species (ROS), inflammation, and autophagy. Qualitative or quantitative analysis of the components of these potential mechanisms was performed by Western blotting (WB), immunofluorescence (IF), quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA).Results: Piperine enhanced the functional recovery of spinal cord injury. Additionally, piperine inhibited inflammation, attenuated oxidative stress and pyroptosis, and activated autophagy. However, the effects of piperine on the functional recovery of SCI, ROS-mediated autophagy, inflammation and pyroptosis were reversed by the inhibition of autophagy.Conclusions: Our experiments demonstrated that piperine facilitated the functional recovery of spinal cord injury by inhibiting the inflammatory response, oxidative stress and pyroptosis, which are mediated by the activation of autophagy.