Accurate animal models are essential for elucidating the pathogenesis of ulcerative colitis (UC). The widely used dextran sodium sulfate-induced UC (DSS-UC) model inadequately reflects the refractory nature of human UC. This study compared the traditional Chinese medicine (TCM)-based SKYD-UC model with the DSS-UC model to identify a more representative model. Network pharmacology was used to analyze the fundamental TCM syndrome of UC and to identify differential targets and pathways between DSS-UC and SKYD-UC. Both UC animal models were subsequently established, and body weight, organ indices, disease activity index (DAI) scores, colon length, mucosal damage, and serum biomarkers (IL-6, TNF-α, MPO, GSH-Px, GAS, and MTL) were evaluated. Among the seven TCM syndromes, SKYD-UC presented the greatest number of targets and pathways, highlighting its fundamental importance. Specifically, 464 and 703 unique targets were identified for DSS-UC and SKYD-UC, respectively. DSS-UC unique targets were predominantly associated with inflammation, immune regulation, and cellular signaling. In contrast, SKYD-UC targets encompass a broader range of biological processes, including mitochondrial dysfunction, extracellular matrix remodeling, and pathways related to systemic UC complications. These findings were validated in animal experiments. Compared with the DSS-UC model, the SKYD-UC model demonstrated more severe damage, including pronounced spleen and thymus atrophy ( p < 0.01), higher DAI scores ( p < 0.01), shorter colons ( p < 0.05), worse inflammation (elevated IL-6 and MPO) and gastrointestinal dysfunction (reduced GAS and elevated MTL) ( p < 0.01), and unique kidney yang deficiency damage (elevated kidney index, p < 0.01), along with sustained weight loss. While both models reflect inflammation and immune dysregulation, the SKYD-UC model better simulates the refractory nature of UC, offering an effective animal model for UC research. We present our manuscript entitled A comparative study of dextran sodium sulfate-induced and spleen-kidney syndrome-based ulcerative colitis. This study aims to address the limitations of current animal models for ulcerative colitis (UC) and, for the first time, integrates the core Traditional Chinese Medicine (TCM) pathogenesis of Spleen-Kidney Yang Deficiency (SKYD) with modern experimental methodologies. We believe our work possesses the following key highlights: • Network analysis identifies SKYD as the fundamental TCM syndrome of UC. • First SKYD-UC rat model established integrating TCM theory and modern biology. • SKYD-UC model mimics the refractory nature of UC better than DSS-UC. • Specific kidney yang deficiency damages and sustained weight loss are unique to SKYD-UC.
Yang et al. (Mon,) studied this question.