Tremella fuciformis Polysaccharides Alleviate Early Brain Injury in Experimental Subarachnoid Hemorrhage by Inhibiting the KDR-Mediated P38 MAPK/NF-κB Pathway.

Subarachnoid hemorrhage (SAH) is associated with high mortality and morbidity rates. In its early stages, a substantial influx of blood into the subarachnoid space triggers excessive activation of microglia, which markedly contributes to early brain injury (EBI), a pivotal determinant of poor prognosis. Tremella fuciformis polysaccharides (TFPSs), as acidic heteropolysaccharides from the fruiting bodies of Tremella, exhibit robust anti-inflammatory characteristics and many biological properties. Nonetheless, the impact of TFPSs on EBI after SAH has yet to be reported, and the molecular mechanisms underlying these effects remain elusive. We used in vivo and in vitro models to study the effects of TFPSs on microglia post-SAH. Network pharmacology analysis was used to predict the targets of TFPSs and the pathways through which it exerts its therapeutic effects. These predictions were subsequently corroborated through flow cytometry, Western blotting, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), and quantitative real‑time polymerase chain reaction, both in vivo and in vitro. After 24 h post-SAH, TFPS-treated mice presented improved neurological function and reduced cerebral edema. TFPSs reversed microglial activation, enhanced phagocytic ability, and reduced neuronal apoptosis. Network pharmacology identified KDR as a potential target of TFPSs, with the P38 MAPK pathway as the downstream pathway. TFPSs attenuated KDR expression, inhibited the P38 MAPK/NF-κB pathway, reduced inflammatory cytokine expression, and increased microglial phagocytic capacity post-SAH. This investigation revealed that TFPSs may ameliorate EBI after SAH, potentially via the regulation of the KDR-mediated P38 MAPK/NF-κB pathway and phagocytic function.