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Updated: Jul 16, 2025
Chinese Herbal Retention Enema for the Treatment of Ulcerative Colitis
Published on: May 16, 2025
Sanguisorba officinalis ethyl acetate extract attenuates ulcerative colitis through inhibiting PI3K-AKT/NF-κB/ STAT3
Congcong Li1, Leiqiang Gong1, Yu Jiang2
1State Key Laboratory of Southwestern Chinese Medicine Resource, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Background:
Ulcerative colitis (UC) accounts for the untreatable illness nowadays. Bloody stools are the primary symptom of UC, and the first-line drugs used to treat UC are associated with several drawbacks and negative side effects. S. officinalis has long been used as a medicine to treat intestinal infections and bloody stools. However, what the precise molecular mechanism, the exact etiology, and the material basis of the disease remain unclear.
Purpose:
This work aimed to comprehensively explore pharmacological effects as well as molecular mechanisms underlying the active fraction of S. officinalis, and to produce a comprehensive and brand-new guideline map of its chemical base and mechanism of action.
Methods:
First, different polarity S. officinalis extracts were orally administered to the DSS-induced UC model mice for the sake of investigating its active constituents. Using the UPLC-orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS) technique, the most active S. officinalis (S. officinalis ethyl acetate fraction, SOEA) extract was characterized. Subsequently, the effectiveness of its active fraction on UC was evaluated through phenotypic observation (such as weight loss, colon length, and stool characteristics), and histological examination of pathological injuries, mRNA and protein expression. Cell profile, cell-cell interactions and molecular mechanisms of SOEA in different cell types of the colon tissue from UC mice were described using single-cell RNA sequencing (scRNA-seq). As a final step, the molecular mechanisms were validated by appropriate molecular biological methods.
Results:
For the first time, this study revealed the significant efficacy of SOEA in the treatment of UC. SOEA reduced DAI and body weight loss, recovered the colon length, and mitigated colonic pathological injuries along with mucosal barrier by promoting goblet cell proliferation. Following treatment with SOEA, inflammatory factors showed decreased mRNA and protein expression. SOEA restored the dynamic equilibrium of cell profile and cell-cell interactions in colon tissue. All of these results were attributed to the ability of SOEA to inhibit the PI3K-AKT/NF-κB/STATAT pathway.
Conclusions:
By integrating the chemical information of SOEA derived from UPLC-Q-Orbitrap-HRMS with single-cell transcriptomic data extracted from scRNA-seq, this study demonstrates that SOEA exerts the therapeutic effect through suppressing PI3K-AKT/NF-B/STAT3 pathway to improve clinical symptoms, inflammatory response, mucosal barrier, and intercellular interactions in UC, and effectively eliminates the interference of cellular heterogeneity.
Insights
This study shows Salvia officinalis ethyl acetate fraction (SOEA) effectively treats ulcerative colitis (UC) by inhibiting the PI3K-AKT/NF-κB/STAT3 pathway. It improves symptoms, reduces inflammation, and restores the gut barrier, offering a new therapeutic avenue for UC patients.
Area of Science:
- Pharmacology
- Gastroenterology
- Molecular Biology
Background:
- Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options and significant side effects from current therapies.
- Salvia officinalis (S. officinalis) has a traditional use in treating intestinal issues, but its precise mechanisms in UC are not well understood.
Purpose of the Study:
- To investigate the pharmacological effects and molecular mechanisms of S. officinalis active fraction in treating ulcerative colitis.
- To create a detailed map of the chemical constituents and their action mechanisms.
Main Methods:
- S. officinalis extracts were tested in DSS-induced UC mice models.
- The active ethyl acetate fraction (SOEA) was identified using UPLC-Q-Orbitrap-HRMS.
- Efficacy was assessed via phenotypic, histological, and molecular analyses, including single-cell RNA sequencing (scRNA-seq).
Main Results:
- SOEA significantly ameliorated UC symptoms, including weight loss and colon damage, by promoting goblet cell proliferation.
- SOEA treatment reduced inflammatory markers and restored colonic tissue homeostasis and cell-cell interactions.
- Therapeutic effects were linked to the inhibition of the PI3K-AKT/NF-κB/STAT3 signaling pathway.
Conclusions:
- SOEA demonstrates significant therapeutic potential for ulcerative colitis.
- The study integrates chemical and transcriptomic data to elucidate SOEA's mechanism via PI3K-AKT/NF-κB/STAT3 pathway inhibition.
- SOEA effectively addresses clinical symptoms, inflammation, mucosal barrier function, and cellular heterogeneity in UC.
