2. Academic Validation
  3. Tauroursodeoxycholic acid modulates neuroinflammation via STING/NF-κB inhibition after traumatic brain injury

Tauroursodeoxycholic acid modulates neuroinflammation via STING/NF-κB inhibition after traumatic brain injury

  • Int Immunopharmacol. 2025 Sep 6:165:115471. doi: 10.1016/j.intimp.2025.115471.
Jiawei Xu 1,  Yangyang Luo 1,  Fang Lu 2,  Xiaozhong Xu 3,  Chenlong Jiang 4,  Meili Kang 1,  Cuicui Chang 1,  Hong Wei 5,  Tianlin Long 3,  Bin Jiang 6,  Yuhua Chen 7
Affiliations

Affiliations

  • 1 Department of Medical Science Research Center, Brain Injury and Drug Prevention Research Key Laboratory of Shaanxi Universities, Peihua University, Xi'an, Shaanxi 710125, China.
  • 2 School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Research Team of Regulation of Cellular Senescence and Death, Hainan University, Haikou, Hainan 570100, China.
  • 3 Department of Neurosurgery, Bijie Traditional Chinese Medicine Hospital, Bijie 551700, China.
  • 4 School of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China.
  • 5 Department of Medical Science Research Center, Brain Injury and Drug Prevention Research Key Laboratory of Shaanxi Universities, Peihua University, Xi'an, Shaanxi 710125, China; Department of Rehabilitation Teaching and Research, Xi'an Siyuan University, Xi'an 710038, China.
  • 6 Department of Neurosurgery, Qilu Hospital of Shandong University (Qingdao), Qingdao, Shandong, 266000, China. Electronic address: jiangbin_2000@163.com.
  • 7 Department of Medical Science Research Center, Brain Injury and Drug Prevention Research Key Laboratory of Shaanxi Universities, Peihua University, Xi'an, Shaanxi 710125, China; Department of Neurosurgery, Bijie Traditional Chinese Medicine Hospital, Bijie 551700, China; School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Research Team of Regulation of Cellular Senescence and Death, Hainan University, Haikou, Hainan 570100, China. Electronic address: chenyuhua.358@163.com.
PMID: 40915187 DOI: 10.1016/j.intimp.2025.115471
Abstract

The incidence of traumatic brain injury (TBI) has demonstrated a marked escalation recently. Nevertheless, there remains a critical paucity of effective drug interventions targeting persistent neuroinflammation-induced damage following TBI. STING/NF-κB axis-induced Pyroptosis emerges as a pivotal mechanism driving persistent neuroinflammation, providing it as a potential target for multi-pathway precision therapeutic in TBI. Tauroursodeoxycholic acid (TUDCA), a bile acid endogenously produced primarily in the liver, has been approved by the FDA due to its potential therapeutic properties, particularly hepatoprotective and anti-inflammatory effects. In this study, we discover that TUDCA effectively improves behavioral deficits caused by TBI in vivo. Then, TUDCA attenuates TBI-induced pathology of neuronal injury and inflammation in mice, which involves in signal transduction of the STING pathway and Pyroptosis pathway. In vitro, TUDCA inhibits STING and NF-κB/NLRP3 pathways driven neuronal Pyroptosis. We find that TUDCA further blocks the nuclear translocation response of IRF3/NF-κB and its activation of downstream transcriptional programs. Mechanistically, TUDCA as a potential STING inhibitor targets the pocket of STING protein. Overall, our results give evidence suggesting that TUDCA serves as a promising therapeutic candidate for TBI, specifically targeting the inflammation mediated damage of neurons.

Keywords

Anti-inflammatory effects; NLRP3 signaling pathway; Pyroptosis; STING signaling pathway; TUDCA; Traumatic brain injury.

Figures
Products