Evodiamine protects against lung ischemia-reperfusion injury by attenuating SYK-associated TLR4/NLRP3 inflammasome activation and ferroptosis-related injury signatures

  • Pulm Pharmacol Ther. 2026 Jun:93:102421. doi: 10.1016/j.pupt.2026.102421.
Wei Peng  1 ,  Baiping Ge  2 ,  Rui Zhang  3 ,  Yunen Liu  4 ,  Changci Tong  4 ,  Chenguang Dong  5
Affiliations
  • 1. Department of Pulmonary and Critical Care Medicine, The People's Hospital of Liaoning Province, Liaoning, 110016, China.
  • 2. Department of Emergency, The People's Hospital of Liaoning Province, Liaoning, 110016, China.
  • 3. Department of Pulmonary and Critical Care Medicine, Liaoning Fangda General Hospital, Liaoning, 110172, China.
  • 4. Shenyang Medical College, No. 146, Huanghe North Street, Shenyang, Liaoning, 110034, China.
  • 5. Department of Pulmonary and Critical Care Medicine, The People's Hospital of Liaoning Province, Liaoning, 110016, China. Electronic address: [email protected].
PMID: 41951097 DOI: 10.1016/j.pupt.2026.102421
Abstract

Lung ischemia-reperfusion (I/R) injury is a major driver of acute lung dysfunction after procedures such as lung transplantation, yet effective pharmacological strategies remain limited. We evaluated whether evodiamine (EVO) mitigates lung I/R injury and explored potential mechanisms. Male C57BL/6 mice underwent left pulmonary hilar occlusion (60 min) followed by reperfusion (120 min) and received EVO, the Syk Inhibitor BAY61-3606, or the combination. Compared with I/R alone, treatment reduced histopathological damage, inflammatory cytokine expression, Apoptosis, and ferroptosis-associated marker changes (iron overload, PTGS2 induction, and loss of GPX4/SLC7A11). EVO was associated with decreased activation of the Syk/TLR4/NLRP3 inflammasome axis, and BAY61-3606 recapitulated several protective effects. Because the mechanistic inference is based on pharmacological inhibition, these findings support-rather than definitively prove-SYK-linked TLR4/NLRP3 signaling as an important node in EVO-mediated protection. Together, the data suggest that evodiamine alleviates acute lung I/R injury in part by restraining inflammatory signaling and modulating ferroptosis-related markers.

Keywords
Evodiamine; Ferroptosis; Lung ischemia-reperfusion injury; NLRP3 inflammasome; SYK; TLR4.
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