1,8-Cineole alleviates spinal cord injury by inhibiting microglial pyroptosis via the P38 MAPK and PI3K/AKT/NLRP3 signaling pathways to protects neurons
- Int Immunopharmacol. 2025 Aug 23:164:115400. doi: 10.1016/j.intimp.2025.115400.
- 1. Department of Orthopedics, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
- 2. Pathology Department, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
- 3. Department of Orthopedics, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China. Electronic address: [email protected].
- 4. Department of Orthopedics, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China. Electronic address: [email protected].
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.