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Title: Exploring the Effects of Scutellaria Baicalensis stem-leaf total flavonoids on Ulcerative Colitis Mice Based on Gut Microbiota and Proteomics

ABSTRACT: Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD). Scutellaria baicalensis Georgi (SBG), a widely used traditional Chinese medicine, exhibits anti-inflammatory and antioxidant properties. Scutellaria Baicalensis stem-leaf total flavonoids (SSTF) ameliorate colonic pathological damage in UC mouse model. However, its mechanism of action remains to be further explored. Aim of study: To investigate the therapeutic effects of SSTF on UC mice and the underlying mechanisms. Materials and methods: Construct a mouse model of UC and evaluate therapeutic efficacy by assessing clinical indicators and histopathological changes. Integrated gut microbiota and proteomics identified core targets associated with SSTF, and target validation was performed by immunohistochemistry. Results: Our results revealed that SSTF significantly improves clinical indicators (colon length, body weight, DAI score, spleen index, TNF-α, IL-10) in UC mice. Pathological damage was reduced, intestinal mucosal barrier impairment was improved, and core proteins (MUC2, ZO-1) were elevated. Proteomics identified 1116 differentially expressed genes. SSTF significantly regulated the intestinal flora structure of UC mice to promote the proliferation of beneficial bacterial genera. Three core targets (NR1D1, AMBRA1, YAP1) were validated by immunohistochemistry, confirming their roles in the treatment of UC with SSTF. Conclusion: SSTF improves UC and attenuates histopathological damage. These findings further elucidate the treatment mechanism of SSTF and provide new ideas for the treatment of UC.

ORGANISM(S): Mus Musculus

SUBMITTER: Fujiang Wang

PROVIDER: PXD075545 | iProX | Wed Mar 11 00:00:00 GMT 2026

REPOSITORIES: iProX

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Project description:BACKGROUND: Ulcerative colitis (UC) is a chronic recurrent inflammatory disease of the gastrointestinal tract. Recent studies demonstrate that the phenolic tannin paeonol (Pae) attenuates UC in mouse models by downregulating inflammatory factors; however, molecular mechanisms linking the gut microbiota and microbial metabolism with Pae remain elusive. METHODS: The UC mouse model was induced using 3% dextran sodium sulfate (DSS). Clinical symptoms were assessed, hematoxylin-eosin staining were used to analyze the effect of Pae on pathological changes to mouse colons, and ELISA was used to evaluate inflammatory factor expression in the serum. Transmission electron microscopy and immunohistochemistry were used to examine the structure of the colonic epithelial barrier and its tight junction proteins. Potential mechanisms of Pae were explored by 16S rRNA-based gut microbiota analysis, fecal metabolomics and construction of a multiscale, multifactorial network. RESULTS: Pae treatment significantly reduced the weight loss and disease activity index, colon shortening, tissue damage, and changes in TNF-α, IL-1β, IL-6, and IL-4 cytokine levels. Conversely, Pae restored the integrity of the intestinal epithelial barrier by increasing the expression of Occludin and ZO-1. Pae also partially reverted the DSS-induced disturbance in intestinal flora composition by increasing the proportion of probiotic bacteria and inhibiting UC-associated dysregulation of gut microbiota metabolites such as bile acids (BA) and short chain fatty acids. Network analysis demonstrated that Lactobacillus was associated with increased levels of unbound BAs, which in turn were strongly associated with inflammatory factor levels. The results suggest that Pae influences BA synthesis by regulating hepatic FXR-SHP/LRH-1 and ileum FXR-FGF15 signaling pathways to maintain intestinal integrity in UC mice. CONCLUSION: Pae can alleviate DSS-induced UC in mice by restoring dysregulated intestinal microbiota and BA metabolism, which improves intestinal barrier function and colonic inflammation, thus suggesting a new mechanism for Pae treatment of UC.

Project description:Background: Ulcerative colitis (UC) is a significant and challenging condition in the digestive system, necessitating the development of effective therapeutic interventions. The Daifu decoction (DFD) is derived from the Lizhong decoction, a classic traditional Chinese Medicine (TCM) formula used to treat digestive diseases. Previous studies have found that DFD has a clear therapeutic effect on UC. This study aimed to investigate the underlying mechanisms of DFD in UC treatment.Methods: A mouse model of dextran sulfate sodium (DSS)-induced UC was established, and mice were treated with DFD using the concentrations 1.6 g/kg/d, 3.2 g/kg/d, and 6.4 g/kg/d for 7 days. H&E and AB-PAS staining, ELISA, qPCR, and immunofluorescence were selected to assess the role of DFD in alleviating colitis and improving intestinal barrier damage. In addition, untargeted metabolomics and transcriptomics helped investigate the potential mechanism of DFD against UC, 16S rRNA sequencing evaluated the characteristics of the gut microbiota. The key target and downstream molecules were verified by molecular docking, molecular dynamics simulation, qPCR, western blotting, and immunohistochemistry.Results: DFD prevented goblet cell loss, downregulated proinflammatory factors in serum, and improved tight junction mRNA and protein expression in colon tissue. Furthermore, DFD decreased the proportion of pathogenic microbes, while increasing the microbiota diversity and the proportion of beneficial bacterial. The integrated multi-omics analysis revealed that PRKCG was the key target of DFD to improve UC. Molecular docking and molecular dynamics simulations further confirmed that the active components of DFD could bind to PRKCG stably. The results of qPCR, western blotting, and immunohistochemistry revealed that DFD could regulate PKCγ/ERK/NF-κB pathway.Conclusion: DFD can exert therapeutic effects on UC by regulating the PKCγ/ERK/NF-κB signaling pathway and the gut microbiota to restore the intestinal barrier and decrease the secretion of proinflammatory cytokines.

Dataset Information

Title: Exploring the Effects of Scutellaria Baicalensis stem-leaf total flavonoids on Ulcerative Colitis Mice Based on Gut Microbiota and Proteomics

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