Alpinetin inhibits neuroinflammation and neuronal apoptosis via targeting the JAK2/STAT3 signaling pathway in spinal cord injury

Abstract

Background A growing body of research shows that drug monomers from traditional Chinese herbal medicines have antineuroinflammatory and neuroprotective effects that can significantly improve the recovery of motor function after spinal cord injury (SCI). Here, we explore the role and molecular mechanisms of Alpinetin on activating microglia‐mediated neuroinflammation and neuronal apoptosis after SCI. Methods Stimulation of microglia with lipopolysaccharide (LPS) to simulate neuroinflammation models in vitro, the effect of Alpinetin on the release of pro‐inflammatory mediators in LPS‐induced microglia and its mechanism were detected. In addition, a co‐culture system of microglia and neuronal cells was constructed to assess the effect of Alpinetin on activating microglia‐mediated neuronal apoptosis. Finally, rat spinal cord injury models were used to study the effects on inflammation, neuronal apoptosis, axonal regeneration, and motor function recovery in Alpinetin. Results Alpinetin inhibits microglia‐mediated neuroinflammation and activity of the JAK2/STAT3 pathway. Alpinetin can also reverse activated microglia‐mediated reactive oxygen species (ROS) production and decrease of mitochondrial membrane potential (MMP) in PC12 neuronal cells. In addition, in vivo Alpinetin significantly inhibits the inflammatory response and neuronal apoptosis, improves axonal regeneration, and recovery of motor function. Conclusion Alpinetin can be used to treat neurodegenerative diseases and is a novel drug candidate for the treatment of microglia‐mediated neuroinflammation.

Conditioned medium of epidermal neural crest stem cells improved functional recovery and tissue repairing after spinal cord injury by suppressing neuronal apoptosis through the PI3K/AKT signaling pathway

“…Injury to the spinal cord leads to irreversible dysfunction or loss of multiple cells and microenvironment imbalance. Neuronal apoptosis is one of the most important pathological mechanisms in SCI [44,45]. In this study, the co-immuno uorescence and western blot results showed that EPI-NCSCs-CM could protect spinal cord neurons from apoptosis.…”

TP53INP2 knockdown inhibits inflammatory response and apoptosis after spinal cord injury

“…LPS induced BV‐2 cells have been widely used in SCI in vitro studies 21,26,27 . In this study, SCI in vitro model was established by treating BV‐2 cells with LPS, and the data indicated that LPS significantly induces apoptosis and inflammatory response in BV‐2 cells, indicating the successful establishment of the model 21,28,29 . However, on the contrary, studies have reported that low‐dose LPS suppresses PC‐12 cell apoptosis, thus reducing SCI damage, 30 which requires further in‐depth investigation.…”

“… 21 , 26 , 27 In this study, SCI in vitro model was established by treating BV‐2 cells with LPS, and the data indicated that LPS significantly induces apoptosis and inflammatory response in BV‐2 cells, indicating the successful establishment of the model. 21 , 28 , 29 However, on the contrary, studies have reported that low‐dose LPS suppresses PC‐12 cell apoptosis, thus reducing SCI damage, 30 which requires further in‐depth investigation. Using the in vivo SCI mouse model and in vitro SCI cell model, we found that TP53INP2 was significantly enhanced in the SCI mouse spinal cord tissue and LPS‐induced BV‐2 cells.…”

Transcranial direct current stimulation-mediated miR-298-5p downregulation enhances autophagy by targeting LC3 to promote motor recovery after spinal cord injury

“…Speci cally, mechanical events can lead to compression and tearing of the spinal cord, which would be referred to as the primary injury. The primary injury is followed by a secondary injury cascade, which consists of the activation of neuronal apoptosis and the inhibition of autophagy ux, which ultimately lead to massive tissue destruction [14,15]. Autophagy is a cellular response that maintains homeostasis in the cell structure and function and exhibits close interactions with apoptosis [16].…”