Network Pharmacology and Bioinformatics Analysis of the Mechanisms Underlying Nao Xue Ping in Intracerebral Hemorrhage Treatment.

INTRODUCTION

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high mortality and limited therapeutic options. Traditional Chinese medicine (TCM), such as Nao Xue Ping (NXP), has shown clinical efficacy in ICH management, but its mechanisms remain unclear.

METHODS

We employed network pharmacology and molecular docking to investigate the mechanisms of NXP. Active compounds were identified using TCMSP and ETCM databases, while GeneCards and OMIM databases provided ICH-related targets. Protein-protein interaction (PPI) networks, functional enrichment analysis, and molecular docking were performed to uncover key pathways and targets. To validate docking results, 100ns MD simulations and MM/GBSA calculations were performed to evaluate dynamic stability and binding free energies, while key targets were further validated using the GEO database.

RESULTS

We identified 11 active compounds and 145 overlapping targets of Nao Xue Ping (NXP) in intracerebral hemorrhage (ICH). Twelve core targets were highlighted through PPI network analysis. Enrichment analyses revealed involvement in inflammation, angiogenesis, and oxidative stress pathways, including PI3KAkt, MAPK, and TNF signaling. Molecular docking confirmed strong binding between key compounds (e.g., rhein, kaempferol) and core targets. Subsequent MD simulations and MM/GBSA calculations verified the dynamic stability of high-affinity complexes, identifying van der Waals interactions as the primary binding driver. GEO validation identified 14 shared genes, with PTGS2 and HSP90AB1 as key therapeutic targets.

DISCUSSION: This study systematically explored the mechanisms of Nao Xue Ping (NXP) in treating intracerebral hemorrhage (ICH) using network pharmacology, enrichment analysis, molecular docking, molecular dynamics (MD) simulations, MM/GBSA calculations, and transcriptomic validation. The results indicate that NXP exerts its therapeutic effects through multiple pathways involved in inflammation, oxidative stress, apoptosis, and angiogenesis. Core targets such as PTGS2 and HSP90AB1 were identified and validated using GEO datasets, highlighting their roles in mediating neuroinflammation, blood-brain barrier disruption, and ferroptosis. Molecular docking revealed strong binding affinities between active compounds (e.g., rhein, kaempferol) and these core targets. These findings provide a mechanistic rationale for the clinical efficacy of NXP and suggest that modulation of PTGS2 and HSP90AB1 pathways may offer promising therapeutic strategies for hemorrhagic stroke.

CONCLUSION

NXP shows significant potential in treating ICH by targeting key pathways and molecules involved in neuroinflammation, oxidative stress, and tissue repair. Future studies should focus on experimental validation and clinical translation to fully elucidate its therapeutic efficacy and mechanisms in ICH management.