Ethnopharmacological Relevance: Compound sophora decoction (CSD), a widely used Chinese herbal formula, has been shown to effectively alleviate symptoms ulcerative colitis (UC), including of bloody diarrhea, tenesmus, abdominal pain, and fever. Despite its clinical use, the precise pharmacological mechanisms of CSD remain enigmatic.
Aim Of The Study: This study aims to investigate the potential efficacy and underlying mechanisms of CSD in the treatment of UC by employing an integrative pharmacology-based approach, molecular docking analysis and experimental validation.
Materials And Methods: In this study, an integrative pharmacology-based approach was employed to predict the primary pathway through which CSD treats UC. The mechanism of CSD was further validated using a DSS-induced UC mouse model. Disease severity was assessed by monitoring stool property, body weight, colon length, and colon histopathology. Colonic pathological changes were examined using hematoxylin and eosin (HE) staining. The concentration of cytokines was measured via ELISA, while key molecules in the PI3K-AKT pathway and autophagy-related markers were evaluated using Western blotting. Autophagy in intestinal epithelial cells was observed using electron microscopy.
Results: The results demonstrated that CSD alleviated DSS-induced UC by inhibiting the activation of PI3K-AKT pathway, reducing the release of inflammatory cytokines, down-regulating oxidative mediators, and enhancing autophagy. Moreover, the protective effects of CSD were diminished by bpV, a PTEN inhibitor, further supporting the involvement of the PI3K-AKT pathway.
Conclusions: The underlying mechanism of CSD's therapeutic effect on UC may involve significant attenuation of DSS-induced intestinal inflammation by promoting autophagy through the inhibition of PI3K-AKT pathway activation.
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| http://dx.doi.org/10.1016/j.jep.2024.118885 | DOI Listing |
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