Novel neuroglobin boosters as a therapeutic strategy for traumatic brain injury.

Neuroglobin (Ngb) induction offers a promising strategy for mitigating traumatic brain injury (TBI) damage due to its intrinsic antioxidant properties and capacity to alleviate oxidative stress. In this study, we employed high-throughput bioinformatics analysis to identify specific compounds that modulate Ngb-related mechanisms, followed by in vitro evaluation of their effects in astrocyte cultures. Among the compounds screened, A1 and A4 emerged as the most potent Ngb inducers. Immunocytochemistry revealed that A1 significantly increased Ngb intensity by 22 %, while A4 enhanced it by 25 %. Additionally, western blot analysis demonstrated that A1 treatment resulted in a threefold increase in Ngb expression compared to controls. Both compounds also improved cell viability, with A1 increasing viability by 8 % and A4 by 25 % relative to untreated controls. Furthermore, our results indicate that these compounds regulate mitochondrial function, enhancing cellular respiration, and potentially reducing energy demand under basal conditions. The complex interactions between Ngb and mitochondrial components, along with their role in various cellular signalling pathways, highlights the need for further research to fully elucidate Ngb's mechanisms of action. In conclusion, compounds A1 and A4 are promising candidates for developing innovative neuroprotective therapies, warranting ongoing exploration of their therapeutic implications.