Gegen Qinlian Decoction improves Alzheimer's disease through TLR4/NF-κB/NLRP3 pathway

Alzheimer's disease (AD) is a neurodegenerative disease that leads to dementia, but effective treatments are lacking. This study aims to evaluate the therapeutic effects of Gegen Qinlian Decoction (GGQLD) on AD and investigate the underlying mechanisms.

Using network pharmacology and bioinformatics, we identified 376 active ingredients of GGQLD and 427 drug targets. Among these, 7 potential targets (CASP1, MKI67, NFKB1, TLR4, NLRP3, IL1B, and AKT1) were identified as intersecting targets of both GGQLD and AD. Functional enrichment analysis revealed that GGQLD regulates pyroptosis-related pathways. In vivo, GGQLD was administered to AD rat models to assess its effects on spatial learning, memory, and brain tissue injury.

GGQLD significantly reduced latency time by 40 % and increased platform crossings by 60 % in AD rats, demonstrating improved spatial learning and memory abilities. It also reduced hippocampal tissue damage and abnormal Aβ deposition. Mechanistically, GGQLD downregulated pyroptosis-related targets (TLR4, NF-κB, NLRP3, IL-1β, and Caspase-1), which were significantly upregulated in AD. ROC analysis demonstrated strong diagnostic significance for these genes, with AUC values exceeding 0.70. Functional enrichment and KEGG analysis further indicated that GGQLD exerts its therapeutic effects through multiple pathways, particularly the NOD-like receptor pathway, Necroptosis, and NF-kappa B pathway.

This study demonstrates that GGQLD improves spatial learning, reduces brain tissue damage, and alleviates inflammation in AD through the regulation of pyroptosis-related pathways, providing evidence for its potential as a therapeutic agent for AD.