Journal of inflammation research · 2025
Integration of Multi-Omics and Network Pharmacology Analysis Reveals the Mechanism of Qingchang Huashi Jianpi Bushen Formula in Repairing the Epithelial Barrier of Ulcerative Colitis.
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Fang Yulai, Min Shichen, Wu Yuguang, Xu Feng, Chen Hongxin, Li Yanan, Lu Yizhou, Hu Jingyi, Zhu Lei, Shen Hong
Аннотация
PURPOSE: Derivation of Qingchang Huashi formula, named Qingchang Huashi Jianpi Bushen (QCHS_JPBS) formula, has shown significant therapeutic effect on patients with ulcerative colitis (UC). In this study, the potential mechanism of QCHS_JPBS formula in repairing mucosal damage was explored from the perspective of intestinal stem cell (ISCs) differentiation, and potential targets of the QCHS_JPBS formula to improve UC were predicted using network pharmacology analysis.
METHODS: The therapeutic efficacy of QCHS_JPBS formula was evaluated in a mouse model of 2.5% dextran sulfate sodium (DSS) induced colitis. The effect of this formula on the ISC differentiation was evaluated using tissue transmission electron microscopy, immunofluorescence, and RT-qPCR. The cecal contents were subjected to 16s RNA sequencing analysis and non-target metabolomics analysis using LC-MS/MS. The fecal microbiota transplantation method verified the essential role of gut microbiota in promoting ISC differentiation and repairing mucosal damage.
RESULTS: The results indicated that QCHS_JPBS formula suppressed the inflammatory response and repaired the damaged intestinal epithelial barrier in DSS-induced colitis mice. QCHS_JPBS formula promoted ISC differentiation, particularly in the direction of goblet cells. QCHS_JPBS formula restored gut dysbiosis and regulated metabolic disorders in DSS-induced colitis mice. And then, the results of fecal microbiota transplantation indicated that QCHS_JPBS formula promoted differentiation of intestinal stem cells to repair mucosal damage through gut microbiota. Finally, a total of 79 active ingredients of QCHS_JPBS formula were identified based on LC-MS analysis and EGFR, STAT3, SRC, AKT1, and HSP90AA1 were considered as potential therapeutic UC targets of QCHS_JPBS formula based on network pharmacology analysis.
CONCLUSION: The present study demonstrated that QCHS_JPBS formula promoted the differentiation of ISCs through gut microbiota to repair the damaged intestinal epithelial barrier in UC mice.
METHODS: The therapeutic efficacy of QCHS_JPBS formula was evaluated in a mouse model of 2.5% dextran sulfate sodium (DSS) induced colitis. The effect of this formula on the ISC differentiation was evaluated using tissue transmission electron microscopy, immunofluorescence, and RT-qPCR. The cecal contents were subjected to 16s RNA sequencing analysis and non-target metabolomics analysis using LC-MS/MS. The fecal microbiota transplantation method verified the essential role of gut microbiota in promoting ISC differentiation and repairing mucosal damage.
RESULTS: The results indicated that QCHS_JPBS formula suppressed the inflammatory response and repaired the damaged intestinal epithelial barrier in DSS-induced colitis mice. QCHS_JPBS formula promoted ISC differentiation, particularly in the direction of goblet cells. QCHS_JPBS formula restored gut dysbiosis and regulated metabolic disorders in DSS-induced colitis mice. And then, the results of fecal microbiota transplantation indicated that QCHS_JPBS formula promoted differentiation of intestinal stem cells to repair mucosal damage through gut microbiota. Finally, a total of 79 active ingredients of QCHS_JPBS formula were identified based on LC-MS analysis and EGFR, STAT3, SRC, AKT1, and HSP90AA1 were considered as potential therapeutic UC targets of QCHS_JPBS formula based on network pharmacology analysis.
CONCLUSION: The present study demonstrated that QCHS_JPBS formula promoted the differentiation of ISCs through gut microbiota to repair the damaged intestinal epithelial barrier in UC mice.