An Exploration of the Active Ingredients of Cortex phellodendri in the Treatment of Hemorrhoids and Its Mechanism Based on Network Pharmacology

Abstract

Background: Huangbo, also known as Cortex phellodendri in Latin, is an important drug which has the pharmacological action of clearing heat, drying dampness, purging fire and detoxifying. In recent years, it has been reported that Huangbo also has the activity of treating hemorrhoids. Objective: The aim of this study was to explore the Active Ingredients of Cortex phellodendri in the Treatment of hemorrhoids and Its Mechanism. Study Design: We analyzed Active components and target genes of Cortex phellodendri in the Traditional Chinese Medicine System Pharmacology (TCMSP) database and analysis platform. We then searched the GeneCards database for target genes related to hemorrhoids and the intersection of these genes with the active components of Cortex phellodendri. Target genes related to hemorrhoids were taken as common potential target genes of Cortex phellodendri, which could act on hemorrhoids. Using the R programming language, we drew a Venn map of these common potential target genes. The “component–target gene–disease” network of Cortex phellodendri in the treatment of hemorrhoids was established using Cytoscape software version 3.7.1; the protein–protein interaction (PPI) network was constructed in the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. With the help of R and Perl languages, we performed gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of potential target genes of Cortex phellodendri in the treatment of hemorrhoids. Results: We extracted a total of 10 active components from Cortex phellodendri, including quercetin and rutaecarpine and so on, as well as 29 potential target genes for hemorrhoids. According to the Degree ranking in Cytoscape3.7.1 software, the top 10 potential target genes were interleukin-6 (IL-6), CCL2, CXCL8, MMP9, vascular endothelial growth factor A (VEGFA), Myc, IL-10, ICAM1, MMP2, and MMP3. Pathway enrichment mainly involved signaling pathways such as advanced glycation end products and receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications, hypoxia-inducible factor 1 (HIF-1), IL-17, and Relaxin. Conclusion: Based on network pharmacology, Cortex phellodendri is expected to be mined as a candidate Traditional Chinese Medicine (TCM) for the treatment of hemorrhoids. Its mechanism for treating this disease operates via multiple components and pathways. This study provides the basic theory and the basis for further research.