Background: The traditional Chinese herbal formula, Danggui Buxue decoction (DBD), is known for its ability in tonifying Qi and promoting the production of blood. It is extensively utilized in treating menstrual anemia and chronic non-healing ulcers. Whereas the impact of DBD on ulcerative colitis (UC) has not been explored, and its therapeutic mechanisms are not well comprehended.

Objective: The research sought to investigate the impacts and mechanisms of DBD on UC through a blend of network pharmacology and experimental confirmation.

Methods: A network pharmacology approach was utilized to predict DBD's potential mechanisms of action on UC, which were then validated through experimental studies using a dextran sulfate sodium (DSS)-induced UC mouse model to assess its protective effects on intestinal injury. Western blot analysis was conducted to examine changes in protein expression within the primary pathway affected by DBD.

Results: A total of 27 active chemical components, 265 potential targets, and 5867 UC target genes were identified through screening. Of these, 172 common targets were found between DBD and UC. Additionally, 2359 GO biological process items and 157 KEGG signal pathways were identified through analysis. Molecular docking revealed strong binding ability between the main compounds and target proteins. In the DSS-induced UC mouse model, DBD reduced intestinal inflammation and attenuated colonic pathological damage, which is associated with DBD's inhibition of the PI3K/AKT pathway.

Conclusions: DBD significantly attenuates colonic inflammation and preserves the integrity of the intestinal mucosa. Furthermore, the anti-UC efficacy of DBD is intricately linked to the suppression of the PI3K/AKT pathway.