Revealing the Molecular Mechanism of Sageretia theezans in the Treatment of Hemorrhoids based on Network Pharmacology

Abstract

Objective: Sageretia theezans is one of the classic medicines in ancient times, which is commonly used to treat scabies, lacquer sores, acute and chronic pharyngitis, Tonsillitis, Cholecystitis, secondary infection of hemorrhoids, and other symptoms. However, the potential molecular mechanism of Sageretia theezans is still unclear. In this study, we explored the active compounds of Sageretia theezans in the treatment of hemorrhoids (HD), predicted the potential targets of drugs, and verified their functions through network pharmacology and in vivo and in vitro experiments. Methods: First, we identified the active compounds and key targets of Sageretia theezans in treating HD through network pharmacology. The key signaling pathways related to the role of Sageretia theezans were analyzed. HUVEC Human umbilical vein endothelial cells were used to study the function of Sageretia theezans and its target in vitro. In addition, we also used the SD rat hemorrhoid model to explore the efficacy of Sageretia theezans in HD in vivo. Result: A total of 159 drug targets were obtained from the TCMSP, ETCM, and PubChem databases. Constructing a drug component target network; differential analysis using sequencing data identified 1046 differentially expressed genes. Intersecting drug targets and differentially expressed genes obtained four intersection targets (GOT1, SLC25A10, SUCLG1, CLEC4E). Perform single gene GSEA functional enrichment analysis on intersection targets, select KEGG and GO of the top 10 for display, and merge the results. In order to investigate the interaction between intersecting genes and differentially expressed genes, we conducted a PPI protein interaction analysis on 1046 differentially expressed genes. Finally, a network of Chinese medicine active molecule intersection genes was proposed, and the genes and their corresponding active molecules (Successful acid, Taraxerone, Taraxerol) were Macromolecular docking, respectively. The results showed that these four genes could be successfully docked with the responsive active molecules and had high binding affinity. In vivo, the low-dose treatment group of Sageretia theezans, the medium-dose treatment group of Sageretia theezans, and the high-dose treatment group of Bromelia can inhibit the proliferation of HUVECs cells. In vitro, the middle dose of Sageretia theezans has the best therapeutic effect on hemorrhoids, and the treatment of Sageretia theezans on hemorrhoids is correlated with the expression of GOT1, SLC25A10, SUCLG1, and CLEC4E. Conclusion: To sum up, Sageretia theezans can alleviate the symptoms of hemorrhoids and is related to the expression of GOT1, SLC25A10, SUCLG1, and CLEC4E.