Neuroprotective effects of carbon dots derived from Gentiana macrophylla Pall. against cerebral ischemia-reperfusion injury via inhibition of MAPK-mediated oxidative stress and inflammation

Ischemic stroke and the ensuing cerebral ischemia-reperfusion injury (CIRI) represent major contributors to mortality and chronic disability among adults on a global scale. Existing therapeutic interventions are often ineffective and fail to address the diverse pathological processes involved in injury progression, highlighting the pressing need for more effective neuroprotective strategies. Capitalizing on the anti-inflammatory and neuroprotective properties of the traditional herbal medicine Gentiana macrophylla Pall., this study successfully synthesized innovative carbon dots derived from this plant (GM-CDs). The experimental findings indicated that GM-CDs effectively scavenged intracellular reactive oxygen species, significantly alleviating oxidative stress damage, restoring normal mitochondrial function, and reducing oxidative DNA damage, thereby inhibiting the apoptotic cascade. Additionally, GM-CDs modulated microglial phenotypic polarization, significantly suppressing their shift towards the pro-inflammatory M1 phenotype and the subsequent secretion of pro-inflammatory cytokines, while simultaneously promoting polarization towards the anti-inflammatory M2 phenotype and enhancing the production of anti-inflammatory cytokines, thus mitigating the cerebral inflammatory response. In a mouse model of CIRI, GM-CDs significantly reduced cerebral infarct volume, effectively inhibited neuronal apoptosis, and notably ameliorated post-surgical neurological deficit symptoms. Transcriptomic analysis revealed that GM-CDs exerted their neuroprotective effects primarily by modulating the activation state of the MAPK signaling pathway. In this study, the nano-transformation of Gentiana macrophylla Pall. was achieved through a facile and eco-friendly approach. The GM-CDs exhibited significant neuroprotection against CIRI, offering a promising therapeutic approach for clinical management.