Therapeutic targets and signal transduction mechanisms of medicinal plant formula Gancao Xiexin decoction against ulcerative colitis: A network pharmacological study

Abstract

<b>Background:</b> Ulcerative colitis (UC) is a chronic disease that often presents with abdominal pain, diarrhea, hematochezia, and significant morbidity. Gancao Xiexin decoction (GXD), a traditional Chinese medicine, has been applied for the clinical treatment of UC, while its action mechanisms are unclear. <b>Methods:</b> The active ingredients and their targets of GXD, and UC-related targets, were derived from public databases. Protein-protein interaction, Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the important active compounds, key targets, and signaling pathways. Then, molecular docking and animal experiments were performed to verify the findings. A total of 213 active compounds and 89 common targets of GXD for UC were obtained. <b>Results:</b> The hub gene network showed <i>ALB</i>, <i>AKT1</i>, <i>IL6</i>, <i>TNF</i>, <i>VEGFA</i>, <i>TP53</i>, <i>CXCL8</i>, <i>MAPK1</i>, <i>PTGS2</i>, and <i>IL1β</i> may be potential targets of GXD against UC. GO and KEGG pathway enrichment analyses suggested that the action of GXD against UC was mainly related to response to oxygen levels, lipopolysaccharide, and molecule of bacterial origin, etc., and achieved by advanced glycation endproducts/receptors for advanced glycation endproducts signaling pathway in diabetic complications, hypoxia-inducible factor (HIF)-1 signaling pathway, interleukin-17/HIF-1 signaling pathway, TNF signaling pathway, etc. Molecular docking results showed that the GXD had good potency of action with the hub target. <i>In vivo</i> experiments showed that GXD significantly alleviated the symptoms of UC and down-regulated the expression of inflammatory factors, nuclear factor-κB and signal transducer and activator of transcription 3. <b>Conclusions:</b> The anti-UC action of GXD is mainly attributed to its anti-oxidative stress, anti-inflammatory, and immunomodulatory functions.