Shaoyao Gancao decoction ameliorates vascular dementia by modulating neuroinflammation and oxidative stress pathways.

BACKGROUND: Vascular dementia (VaD) is a prevalent neurodegenerative disorder for which effective disease-modifying therapies are currently lacking. Shaoyao Gancao Decoction (SGD), a traditional Chinese herbal formula, has demonstrated neuroprotective effects in modern pharmacological studies, suggesting its potential therapeutic value in VaD. OBJECTIVE: The objective of this research was not only to evaluate the therapeutic potential of SGD for VaD but also to decipher its mechanistic basis. METHODS: The prototype components of SGD that enter the brain were identified via UPLC-MS technology. After network pharmacology and in vivo experimental transcriptomics analysis were integrated, key targets and pathways were screened. To further validate the proposed mechanism, we performed molecular docking, molecular dynamics simulations, and in vivo experiments. RESULTS: We identified 18 prototype components of SGD in brain tissue and confirmed that they could significantly ameliorate cognitive deficits and alleviate pathological damage in a VaD rat model. Multiomics integration analysis nominated XDH and EIF2AK2 as candidate targets potentially associated with the regulation of neuroinflammation and oxidative stress through the TLR4/NF-κB/NLRP3 signaling axis. Both molecular dynamics simulations and experimental validation support the therapeutic effects of SGD through the above multitarget and multipathway mechanisms. CONCLUSION: The therapeutic effects of SGD against VaD may involve modulation of the candidate targets XDH and EIF2AK2, together with regulation of the TLR4/NF-κB/NLRP3 signaling axis.