Lihao Shi,1 Leilei Chen,1 Guiyuan Jin,2 Yonghong Yang,2 Fengqin Zhu,3 Guangxi Zhou1,3 

1Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Medical Research Center, Affiliated Hospital of Jining Medical University, Jining, People’s Republic of China; 3Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining, People’s Republic of China

Correspondence: Guangxi Zhou, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China, Tel +86 0537-2903975, Email zgx_viola@126.com

Background: Sini Decoction (SND), a time-honored formulation in traditional Chinese medicine, consists of three key ingredients: aconite, licorice, and ginger rhizome. It has been used for more than a thousand years to relieve symptoms associated with acute gastroenteritis, dyspepsia, and abdominal discomfort, but its therapeutic efficacy in ulcerative colitis (UC) and the mechanisms involved have not been validated. In this study, a comprehensive approach integrating network pharmacology, molecular docking, molecular dynamics simulation and experimentation was used to assess the efficacy of SND in the treatment of UC and to explore its molecular mechanisms.
Methods: The bioactive compounds associated with ulcerative colitis (UC) were identified using the TCMSP database, with potential targets predicted via the Swiss Target Prediction database. Protein-protein interaction networks were constructed using the STRING database and Cytoscape and the most important genes were identified. Subsequently, molecular docking was combined with molecular dynamics simulations using molecular docking to assess the binding affinity of the main active ingredient of SND to AKT1. To evaluate the therapeutic effects of SND, we utilized a dextran sodium sulfate-induced UC mouse model. Additionally, fecal samples were collected for analysis of the intestinal microbiota to explore the influence of SND on gut flora composition.
Results: Fifteen bioactive components from SND were identified, and their activities were validated. The results indicated that AKT serine/threonine kinase 1 is a core target of SND for the treatment of UC. The anti-inflammatory, intestinal barrier-protective, and microbiota-regulating effects of SND were confirmed in animal models, alongside evidence of its inhibitory effect on AKT1.
Conclusion: The active ingredients of SND were screened, with a focus on AKT1 inhibition, to reduce inflammation in UC, protect the intestinal barrier, and regulate the intestinal microbiota, demonstrating significant therapeutic potential.

Keywords: sini decoction, ulcerative colitis, network pharmacology, gut microbiota, intestinal barrier, molecular docking