Potential compounds and mechanism of Scutellariae Radix for improving post-stroke cognitive impairment

Post stroke cognitive impairment (PSCI) is one of the most common complications of stroke, mainly manifested as learning and memory impairment in patients. Various mechanism attribute to the onset PSCI, such as cerebral small vessel disease, lesions in neuroanatomical structures, neuroinflammation and oxidative stress. Scutellariae Radix (SR), a traditional Chinese herbal medicine, has long been used for its anti-inflammatory and antioxidant properties in various diseases.

In clinical practice, the treatment of PSCI primarily relies on symptomatic treatment and rehabilitation therapy. The therapeutic potential of SR compounds in PSCI treatment remains unclear. In this study, we combined network pharmacology and molecular docking to elucidate their mechanisms.

We identified 124 potential SR targets associated with PSCI by analyzing publicly available drug and disease databases. We applied protein-protein interaction (PPI) network analysis, molecular complex detection (MCODE), functional enrichment analysis, molecular docking and molecular dynamics simulation to identify hub genes and elucidate the mechanistic relationships among targets, compounds, and disease pathways.

Through comprehensive analysis, we identified STAT3, BCL2, HIF1A, PPARG, MTOR, PTGS2, MMP9, GAPDH, ESR1, and AKT1 as the top ten hub genes with potential as primary therapeutic targets for PSCI. Functional enrichment analysis suggested that these genes are mainly enriched in the HIF-1 and PI3K-AKT signaling pathways. Network topology analysis identified baicalein as the predominant bioactive component in the phytochemical profile of SR. Molecular docking and molecular dynamics revealed that PTGS2, MMP9, and AKT1 exhibited the lowest binding energy with baicalein.

Baicalein, an active component of SR, may treat PSCI by targeting PTGS2, MMP9, and AKT1 through the PI3K-AKT signaling pathway.