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Updated: Jul 6, 2026
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Xuefu Zhuyu Decoction Ameliorates Neuroinflammation after Traumatic Brain Injury via tRF-3-Leu-AAG/Gpr17 axis
Zhaoyu Yang1, Zhiqiang Yuan2, Jiaqi Hou2
1Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha 410008, PR China; Center for Interdisciplinary Research in Traditional Chinese Medicine, Xiangya Hospital, Central South University, Changsha 410008, PR China; National Clinical Research Center for Geriatric Disease, Xiangya Hospital, Central South University, Changsha 410008, PR China; National Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha 410008, PR China.
Background:
Xuefu Zhuyu Decoction (XFZYD) is clinically applied to traumatic brain injury (TBI) based on its traditional function of activating blood circulation and eliminating stasis. However, its precise mechanism underlying its efficacy, particularly through epigenetic regulation, are poorly understood.
Aim Of The Study:
We hypothesized that the neuroprotective effects of XFZYD post-TBI are mediated through the modulation of transfer RNA-derived small RNAs (tsRNAs), a key class of epigenetic regulators. This study aimed to delineate the specific tsRNA-dependent molecular pathway underlying XFZYD's ability to mitigate neuroinflammation and facilitate neurological recovery.
Materials And Methods:
We employed a murine TBI model treated with XFZYD. Following comprehensive assessment of neurological, histopathological, and inflammatory outcomes to test the mice behavior. The anti-infammatory roles of tRF-3-Leu-AAG was investigated in vivo and in vitro. RNA sequencing and bioinformatics analysis revealed G protein-coupled receptor 17 (Gpr17) is tRF-3-Leu-AAG's target. The direct interaction between tRF-3-Leu-AAG and Gpr17 is validated by dual-luciferase assay. Finally, in vitro rescue experiments conclusively established the tRF-3-Leu-AAG/Gpr17 axis as the functional pathway underlying XFZYD's effects.
Results:
XFZYD administration significantly attenuated neurological deficits, neuronal loss, and rescued cognitive impairment post-TBI. tRF-3-Leu-AAG, as a crucial mediator, which is suppressed by TBI and upregulated by XFZYD. The study demonstrated that tRF-3-Leu-AAG affect the inflammatory response. Critically, the anti-inflammatory and neuroprotective effects of XFZYD were entirely dependent on tRF-3-Leu-AAG. We further delineated the downstream signaling by identifying Gpr17 as a direct and functional target of tRF-3-Leu-AAG. XFZYD mediated tRF-3-Leu-AAG binds to the 3'UTR of Gpr17 mRNA to suppress its expression, thereby inhibiting the Gpr17-induced pro-inflammatory pathway.
Conclusion:
This study elucidates that XFZYD exerts neuroprotection and anti-inflammation after TBI through tRF-3-Leu-AAG/Gpr17 axis. Our findings provide a modern scientific rationale for the application of XFZYD in treating TBI.