Diallyl trisulfide regulates PGK1/Nrf2 expression and reduces inflammation to alleviate neurological damage in mice after traumatic brain injury

Background: Diallyl trisulfide (DATS) has a direct antioxidant capacity and emerges as a promising neuroprotective agent. This study was designed to investigate the role of DATS in traumatic brain injury (TBI).

Methods: TBI mouse models were established using the controlled cortical impact, followed by DATS administration. The effects of DATS on neurological deficit, brain damage, inflammation and phosphoglycerate kinase 1 (PGK1) expression were detected using mNSS test, histological analysis, TUNEL assay, enzyme-linked immunosorbent assay and immunofluorescence. PC12 cells were subjected to H₂O₂-induced oxidative injury after pre-treatment with DATS, followed by cell counting kit-8 assay, flow cytometry and ROS production detection. Apoptosis-related proteins and the PGK1/nuclear factor erythroid-2 related factor 2 (Nrf2) pathway were examined using Western blot.

Results: DATS ameliorated the cerebral cortex damage, neurological dysfunction and Apoptosis, as well as decreased PGK1 expression and expressions of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) in mice after TBI. DATS also enhanced viability, blocked Apoptosis and inhibited ROS production in H₂O₂-induced PC12 cells. DATS downregulated Cleaved-Caspase3, Bax and PGK1 levels, and upregulated Bcl-2 and Nrf2 levels in TBI mouse models and the injured cells.

Conclusion: DATS regulates PGK1/Nrf2 expression and inflammation to alleviate neurological damage in mice after TBI.

Diallyl trisulfide; Neuroprotection; Nuclear factor erythroid-2 related factor 2; Phosphoglycerate kinase 1; Traumatic brain injury.