Tongnao Decoction Exerts a Treatment Effect on Ischemic Stroke by IL-6/PI3K/Akt/GSK-3β Pathway: Based on the Network Pharmacology and Molecular Docking

Ischemic stroke (IS) is an important disease leading to high disability and mortality, and the current clinical treatment is limited. Tongnao Decoction (TND) is a traditional Chinese herbal formula for treating IS, but its pharmacological mechanism remains unclear. This study aims to elucidate the molecular mechanism through network pharmacology, molecular docking, and related experimental verification. First, the bioactive components of TND, along with their potential targets and IS-related gene targets, were identified through multiple databases. Subsequently, an "herb-active component-disease gene target" network and a protein-protein interaction (PPI) network were constructed. Combined with enrichment analysis, key biological processes and signaling pathways were identified. Following this, molecular docking experiments were conducted to preliminarily validate drug-target interactions. Finally, the efficacy of the relevant pathway targets was validated in a photochemically induced mouse cerebral ischemia model. A total of 90 active compounds and 615 target genes were screened. PPI network analyses suggested that TP53, EGFR, STAT3, AKT1, and IL-6 were the hub targets. TND significantly modulates inflammatory biological processes and the PI3K-Akt signaling pathway during IS treatment. Molecular docking analysis indicated that the primary components of TND may exhibit favorable binding affinity to multiple hub target proteins, including TP53, EGFR, STAT3, AKT1, and IL-6. Further in vivo experiments showed that TND dramatically improved neurological function, reduced neuronal damage, and decreased IL-6 expression in brain tissue. In addition, TND stimulated the PI3K/Akt/GSK-3β pathway. These findings imply that TND and its key bioactive components, coryincine, dihydrocapsaicin, and 4 (4'-hydroxybenzyloxy)benzyl methylether exert therapeutic effects on IS through the IL-6/PI3K/Akt/GSK-3β pathway.