Canine cognitive dysfunction (CCD) is a progressive neurodegenerative disorder in aging dogs, sharing significant pathological similarities with human Alzheimer's disease (AD), such as amyloid-beta deposition and neuroinflammation. Yukgunja-tang (YGJ), a traditional herbal formula, has been reported to alleviate psychological symptoms via the gut-brain axis. However, its molecular mechanisms in treating CCD remain unclear. This study was about a network pharmacology approach to elucidate the multi-component, multi-target mechanisms of YGJ against CCD. Active compounds and relates of YGJ drugs and CCD targets were retrieved from the TCMSP (Traditional Chinese Medicine Systems Pharmacology database and analysis platform) and GeneCards databases, respectively. We identified 148 common targets between YGJ drugs and CCD symptom. A protein-protein interaction (PPI) network analysis revealed key hub genes, including TNF (tumor necrosis factor), IL1B (interleukin 1 beta), AKT1 (Ak strain transforming 1), TP53 (tumor protein 53), and IL10 (interleukin 10), which are predominantly involved in inflammation and cell survival. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis indicated that these targets are significantly enriched in the age-rage signaling pathway and cancer pathways, suggesting mechanisms involving the regulation of neuroinflammation and oxidative stress. These findings hypothesize that YGJ exerts therapeutic effects on CCD through a holistic approach: inhibiting neuroinflammation, modulating age-related cellular stress, and regulating cell signaling cascades. This study provides a scientific basis for YGJ as a potential integrative treatment for improving the quality of life in dogs with CCD.

• Minho Park(Department of Animal Health and Welfare, Hoseo University, Asan 31499, Korea)
• Heejin Ham(Department of Animal Health and Welfare, Hoseo University, Asan 31499, Korea) Corresponding author