Si-Ni Decoction as a Potential Treatment for Ulcerative Colitis: Modulation of Gut Microbiota and AKT1 Inhibition Through Network Pharmacology and in vivo Validation

Background: Sini Decoction (SND), a classic formula in traditional Chinese medicine composed of aconite, licorice, and ginger rhizome, has been used for over a thousand years to treat acute gastroenteritis, dyspepsia, and abdominal discomfort. However, its therapeutic potential and underlying mechanisms in ulcerative colitis (UC) remain unverified. This study employed an integrated approach—including network pharmacology, molecular docking, molecular dynamics simulations, and in vivo experiments—to evaluate the efficacy of SND in UC treatment and to elucidate its molecular mechanisms.
Methods: Bioactive compounds related to UC were identified from the TCMSP database, and their potential targets were predicted using the Swiss Target Prediction tool. Protein-protein interaction (PPI) networks were constructed via the STRING database and analyzed using Cytoscape to pinpoint key target genes. Molecular docking and dynamics simulations were performed to assess the binding affinity between SND’s main active component and AKT1. The therapeutic effect of SND was evaluated using a dextran Borussertib sulfate sodium (DSS)-induced UC mouse model. Fecal samples were also analyzed to examine the impact of SND on gut microbiota composition.
Results: Fifteen active components of SND were identified and validated. AKT1 emerged as a central therapeutic target. In vivo studies confirmed the anti-inflammatory effects of SND, along with its role in protecting the intestinal barrier and modulating gut microbiota. Molecular analyses also demonstrated that SND inhibits AKT1 activity.
Conclusion: SND exhibits significant therapeutic potential in UC through inhibition of AKT1, leading to reduced inflammation, enhanced intestinal barrier function, and modulation of gut microbiota. These findings provide a scientific basis for its traditional use and support its potential as a treatment for UC.