The potential mechanism of qinghua quyu jianpi decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic and recurrent inflammation of the gastrointestinal tract. Following the idea of herbal property and compatibility, a traditional Chinese medicine (TCM) formula consists of a number of TCM herbs. Qinghua Quyu Jianpi Decoction (QQJD) has been clinically proven to be effective in treating UC, however, its therapeutic mechanism has not been fully elucidated.

AIM OF STUDY: Here, we used network pharmacology analysis and ultra-performance liquid chromatography-tandem mass spectrometry to predict the mechanism of action of QQJD, and then validated our predictions through in vivo and in vitro experiments.

MATERIALS AND METHODS: First, based on a number of datasets, relationship network diagrams between QQJD and UC were created. The target network for the QQJD-UC intersection genes was then built, and KEGG analysis was carried out to identify a potential pharmacological mechanism. Finally, the results of the previous prediction were validated in dextran sulfate sodium salt (DSS) induced UC mice and a cellular inflammatory model.

RESULTS: Network pharmacology results suggested that QQJD may play a role in repairing intestinal mucosa by activating Wnt pathway. In vivo experiments have shown that QQJD can significantly reduce weight loss, disease activity index (DAI) score, improve colon length, and effectively repair the tissue morphology of UC mice. In addition, we also found that QQJD can activate the Wnt pathway to promote epithelial cell renewal, reduce apoptosis, and repair the mucosal barrier. To further understand how QQJD promotes cell proliferation in DSS-induced Caco-2 cells, we performed a study in vitro experiment. We were surprised to find that QQJD activated the Wnt pathway by inducing nuclear translocation of β-catenin, accelerating the cell cycle and promoting cell proliferation in vitro.

CONCLUSION: Taken together, network pharmacology and experiments showed that QQJD achieves mucosal healing and restores the colonic epithelium barrier by activating Wnt/β-catenin signaling, regulating cell cycle progression, and promoting the proliferation of epithelial cells.