1,8-Cineole alleviates spinal cord injury by inhibiting microglial pyroptosis via the P38 MAPK and PI3K/AKT/NLRP3 signaling pathways to protects neurons

• Published in: International immunopharmacology Vol. 164; p. 115400
• Main Authors: Zhou, Wenyang, Liu, Zhenhao, Qiu, Xichuan, Tian, Minghao, He, Baoqiang, Tang, Chao, Tang, Qiang, Ye, Rupei, Zhong, Dejun, Liao, Yehui
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 30.10.2025
• Subjects: 1,8-Cineole; Microglial pyroptosis; Nerve regeneration; Network pharmacology; NLRP3; PI3K/AKT; Spinal cord injury; 1,8-Cineole; Microglial pyroptosis; NLRP3; Network pharmacology; Spinal cord injury; Nerve regeneration; PI3K/AKT
• ISSN: 1567-5769
• DOI: 10.1016/j.intimp.2025.115400

Following spinal cord injury (SCI), pyroptosis plays a significant role in regulating neuroinflammation during the secondary phase of injury. Although 1,8-cineole possesses anti-inflammatory effects, its role in SCI and underlying molecular mechanisms remains unclear. This study revealed that 1,8-cineole promoted motor function recovery in spinal cord-injured rats, reduced NLRP3 inflammasome-mediated microglial pyroptosis and activation, enhanced neuronal regeneration, and suppressed neuronal apoptosis and glial scar formation. Network pharmacology analysis showed that 1,8-cineole targets the PI3K/AKT and P38 MAPK pathways to inhibit microglial activation and pyroptosis. Finally, using a conditional co-culture system, we demonstrated that 1,8-cineole-treated microglia facilitated neuronal regeneration while inhibiting apoptosis. These findings indicate that 1,8-cineole promotes functional recovery post-SCI by protecting neurons by suppressing microglial pyroptosis and activation through the PI3K/AKT and P38 MAPK axes. •The mechanism of action of the active ingredient 1,8-cineole from traditional Chinese medicine in spinal cord injury is described for the first time, which aligns with the purpose of your esteemed publication.•The repair of spinal cord injury is a result of the mutual regulation of various cells in the body. Our exploration of the role played by 1,8-cineole in the interaction between microglia and neurons bears a certain degree of novelty.•Network pharmacology is widely used in the study of traditional Chinese medicine. We applied it to understand the underlying mechanism of 1,8-cineole in alleviating spinal cord injury, and conducted relatively detailed experimental verification.