Subarachnoid hemorrhage (SAH) is a life-threatening neurological emergency associated with high mortality and poor functional outcomes. Early brain injury (EBI) within the first 72 h critically influences prognosis, with excessive microglial activation representing a key contributor to neuroinflammation and secondary neuronal damage. Identifying pharmacological agents capable of modulating microglia-driven inflammatory responses remains an important therapeutic challenge. In this study, we investigated the potential anti-inflammatory mechanisms of pinostrobin (PIN), a natural flavonoid with reported neuroprotective properties. By integrating bioinformatics, network pharmacology, and machine learning approaches (LASSO, random forest, and SVM), MYC and CTSL were identified as candidate targets potentially linking PIN to SAH-related inflammatory pathways. Molecular docking and 50-ns molecular dynamics simulations suggested stable interactions between PIN and these proteins. Furthermore, in vitro evidence from LPS-stimulated BV2 microglial cells demonstrated that PIN reduced the expression of MYC, CTSL, NF-κB p65, and IL-1β, accompanied by attenuation of microglial inflammatory activation. Collectively, these findings suggest that PIN may modulate neuroinflammatory cascades relevant to EBI after SAH, potentially through regulation of the MYC-CTSL axis. This study provides integrative, hypothesis-generating insights into the microglia-targeted anti-inflammatory potential of PIN in the context of SAH.
Liu et al. (Wed,) studied this question.