Objective: Sanguisorba officinalis L. and Sophora japonica L. (SOSJ) have been frequently used as medicinal pairs for treating ulcerative colitis (UC) due to their hemostatic properties. However, the mechanisms underlying their therapeutic effects remain unclear. This study aims to predict the targets of SOSJ for UC treatment using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS) and network pharmacology.

Methods: The efficacy of SOSJ was evaluated using a 3% dextrose sodium sulfate (DSS)-induced UC mice model. The general condition of the mice, histopathology, and expression of colonic inflammatory factors were assessed. Additionally, the effect of SOSJ on angiogenesis was evaluated by detecting the mRNA of colonic angiogenesis-related mediators, measuring microvessel density, and using transmission electron microscopy.

Results: SOSJ significantly attenuated inflammation and inhibited pathological angiogenesis in UC mice. It alleviated weight loss, colon shortening, and the presence of pus and blood in stools. SOSJ also reduced the mRNA expression levels of IL-6, IL-1β, TNF-α, VEGF, VCAM1, Ang1, MMP1, MMP2, and MMP9. Furthermore, SOSJ decreased the protein expression of the PI3K-Akt pathway, an effect that could be reversed by 740Y-P, a specific PI3K activator.

Conclusions: S. officinalis L. and S. japonica L. exert therapeutic effects on mice with ulcerative colitis, potentially through the modulation of angiogenesis and the PI3K-Akt signalling pathway.