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

• Published in: Inflammation research Vol. 73; no. 11; pp. 1981 - 1994
• Main Authors: Zhang, Bin, Yu, Jiasheng, Bao, Lei, Feng, Dongqian, Qin, Yong, Fan, Daobo, Hong, Xin, Chen, Yongyi
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.11.2024; Springer Nature B.V
• Subjects: Allergology; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Artichokes; Biomedical and Life Sciences; Biomedicine; Cell death; Cell Line; Damage; Dermatology; Immunology; Inflammasomes; Inflammation; Limbs; Male; Mice; Mice, Inbred C57BL; Microglia; Microglia - drug effects; Microglia - metabolism; Neuroinflammatory Diseases - drug therapy; Neurology; Neuropathy; NF-E2-Related Factor 2 - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Original Research Paper; Oxygen; Pharmacology/Toxicology; Proteins; Pyroptosis; Pyroptosis - drug effects; Reactive oxygen species; Reactive Oxygen Species - metabolism; Rheumatology; Spinal cord injuries; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Cynarin; NLRP3; Pyroptosis; Spinal cord injury; Nrf2; Microglia
• ISSN: 1023-3830; 1420-908X; 1420-908X
• DOI: 10.1007/s00011-024-01945-x

Highlights Cynarin decreases neuroinflammation levels and attenuates microglial pyroptosis. Cynarin hinders the formation of NLRP3 inflammasome through Nrf2-dependent expression. Cynarin-treated mice showed lower levels of reactive oxygen species (ROS) and cell death, as well as reduced neurohistological damage, and improved hindlimb locomotor function compared to untreated mice. 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.