Cynarin inhibits microglia-induced pyroptosis and neuroinflammation via Nrf2/ROS/NLRP3 axis after spinal cord injury

Background: Spinal cord injury (SCI) elicits excess neuroinflammation and resident microglial Pyroptosis, leading further terrible neurological collapse and locomotor dysfunction. However, the current clinical therapy is useless and a feasible treatment is urgent to be explored. Cynarin is a natural component in artichoke playing anti-inflammatory and Anti-aging roles in hepatoprotection and cardioprotection, but it is unclear that the pharmacologic action and underlying mechanism of Cynarin in neuropathy.

Methods: Using the SCI mouse model and the BV2 cell line, we here investigated whether Cynarin reduces neuroinflammation and Pyroptosis to promote neurological recovery after SCI.

Results: Our results showed that treatment with Cynarin reduces the level of neuroinflammation and microglial Pyroptosis. Moreover, the mice treated with Cynarin exhibited lower level of Reactive Oxygen Species (ROS) and cell death, less damage of neurohistology and better locomotor improvement of hindlimbs than the untreated mice and the nuclear factor erythroid 2-related factor 2 (Nrf2)-inhibited mice. Mechanically, Cynarin inhibited the assembly of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome by Nrf2-dependent expression to attenuate microglial Pyroptosis and neuroinflammation.

Conclusions: To sum up, the current study suggested that administration of Cynarin is a promising compound for anti-neuroinflammation and anti-pyroptosis after SCI. It may be an efficient Nrf2 activator and a NLRP3 Inhibitor for microglia in neuropathies.

Cynarin; Microglia; NLRP3; Nrf2; Pyroptosis; Spinal cord injury.