Network pharmacology and molecular docking–based investigation of monocyte locomotion inhibitory factor attenuates traumatic brain injury by regulating aquaporin 4 expression

Traumatic brain injury (TBI) is a significant cause of disability and mortality worldwide, and effective treatment options are currently limited. Monocyte locomotion inhibitor factor (MLIF), a small molecular pentapeptide, has demonstrated a protective effect against cerebral ischemia. This study aimed to investigate the protective effects of MLIF on TBI and explore its underlying mechanism of action. In animal experiments, we observed that administration of MLIF after TBI reduced brain water content and improved brain edema, suggesting a certain degree of protection against TBI. By utilizing network pharmacology methodologies, we employed target screening techniques to identify the potential targets of MLIF in the context of TBI. As a result, we successfully enriched ten signaling pathways that are closely associated with TBI. Furthermore, using molecular docking techniques, we identified AQP4 as one of the top ten central genes discovered in this study. Eventually, our study demonstrated that MLIF exhibits anti-apoptotic properties and suppresses the expression of AQP4 protein, thus playing a protective role in traumatic brain injury. This conclusion was supported by TUNEL staining and the evaluation of Bcl-2, Bax, and AQP4 protein levels. These discoveries enhance our comprehension of the mechanisms by which MLIF exerts its protective effects and highlight its potential as a promising therapeutic intervention for TBI treatment.