2. Academic Validation
  3. 1,8-Cineole alleviates spinal cord injury by inhibiting microglial pyroptosis via the P38 MAPK and PI3K/AKT/NLRP3 signaling pathways to protects neurons

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.
Wenyang Zhou 1,  Zhenhao Liu 1,  Xichuan Qiu 1,  Minghao Tian 1,  Baoqiang He 1,  Chao Tang 1,  Qiang Tang 1,  Rupei Ye 2,  Dejun Zhong 3,  Yehui Liao 4
Affiliations

Affiliations

  • 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: zdj_1974@163.com.
  • 4 Department of Orthopedics, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China. Electronic address: lyh_spine@163.com.
PMID: 40850199 DOI: 10.1016/j.intimp.2025.115400
Abstract

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.

Keywords

1,8-Cineole; Microglial pyroptosis; NLRP3; Nerve regeneration; Network pharmacology; PI3K/AKT; Spinal cord injury.

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