The Effect and Potential Pharmacological Mechanism of Tauroursodeoxycholic Acid for Spinal Cord Injury: A Systematic Review and Network Pharmacology.

BACKGROUND

Spinal Cord Injury (SCI) is a highly disabling disease owing to unexpected mechanical damage, which may trigger serious complications. Tauroursodeoxycholic Acid (TUDCA) serves as a neuroprotective agent for SCI. Therefore, this study assessed the effect of TUDCA for intervening in SCI in existing preclinical tests, with a summary of its mechanism simultaneously.

METHODS

This systematic review was presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. Literature retrieval, without language restriction, to identify in vivo studies on SCI treatment using TUDCA was performed by searching databases such as PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and SinoMed from their inception to May 2025, coupled with the collection of grey literature. Literature retrieval and risk-of-bias assessment using SYRCLE's RoB tool were independently conducted by two reviewers. A subsequent meta-analysis was conducted using the Review Manager 5.4 software. In addition, network pharmacology combined with molecular docking was utilized to explore the potential mechanism of TUDCA in treating SCI.

RESULTS

A total of 14 studies were finally enrolled, over half of which had at least 5 items rating low risk of bias. The results of the meta-analysis showed that motor function, as assessed by the BBB score, was significantly enhanced after TUDCA treatment (14th day; WMD = 3.11 [1.84 to 4.37], p < 0.0001). Meanwhile, the inclined plane test and TUNEL indicated that TUDCA contribut-ed to SCI recovery. Subgroup analysis suggested a more pronounced effect of TUDCA in females (WMD = 3.76 [2.51, 5.10], p < 0.0001) than in males. Moreover, TUDCA at 200 mg/kg improved motor function (WMD = 2.90 [2.03, 3.77]; p < 0.0001). Network pharmacology identified AKT1, EGFR, HSP90AA1, and SRC as key targets, with the identification of PI3K-Akt, Foxo, estrogen signaling pathway, and apoptosis, etc. Molecular docking suggested that PPARγ, PARP1, and GSK3β bound to TUDCA better. Additionally, this review revealed the unique advantages and potential mechanisms of TUDCA, supporting the potential of neuroprotective agents for SCI treatment.

DISCUSSION: The identified optimal dose and sex-dependent efficacy of TUDCA provide critical insights for its future development as a neuroprotective agent. Network pharmacology and molecular docking provide sufficient evidence for SCI treatment with TUDCA.

CONCLUSION

TUDCA can enhance neuronal autophagy and inhibit inflammatory factor expression, reducing inflammatory response and suppressing neuronal apoptosis in SCI. Due to the limited number and uneven quality of included studies, further laboratory studies and validation in clinical trials are necessary to clarify the neuroprotective effect of TUDCA.