The Efficacy and Underlying Pathway Mechanisms of ShiDuGao Treatment for Anus Eczema Based on GEO Datasets and Network Pharmacology

Summary

This investigative effort sought to elucidate the mechanism of topical drug administration using a synergistic integration of network pharmacology and gene expression omnibus (GEO) datasets. This article evaluated the feasibility, target, and mechanism of ShiDuGao (SDG) in treating anus eczema.

Abstract

Anus eczema is a chronic and recurrent inflammatory skin disease affecting the area around the anus. While the lesions primarily occur in the anal and perianal skin, they can also extend to the perineum or genitalia. ShiDuGao (SDG) has been found to possess significant reparative properties against anal pruritus, exudation control, moisture reduction, and skin repair. However, the genetic targets and pharmacological mechanisms of SDG on anal eczema have yet to be comprehensively elucidated and discussed. Consequently, this study employed a network pharmacological approach and utilized gene expression omnibus (GEO) datasets to investigate gene targets. Additionally, a protein-protein interaction network (PPI) was established, resulting in the identification of 149 targets, of which 59 were deemed hub genes, within the "drug-target-disease" interaction network.

The gene function of SDG in the treatment of perianal eczema was assessed through the utilization of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. Subsequently, the anti-perianal eczema function and potential pathway of SDG, as identified in network pharmacological analysis, were validated using molecular docking methodology. The biological processes associated with SDG-targeted genes and proteins in the treatment of anus eczema primarily encompass cytokine-mediated responses, inflammatory responses, and responses to lipopolysaccharide, among others. The results of the pathway enrichment and functional annotation analyses suggest that SDG plays a crucial role in preventing and managing anal eczema by regulating the Shigellosis and herpes simplex virus 1 infection pathways. Network pharmacology and GEO database analysis confirms the multi-target nature of SDG in treating anal eczema, specifically by modulating TNF, MAPK14, and CASP3, which are crucial hub targets in the TNF and MAPK signaling pathways. These findings provide a clear direction for further investigation into SDG's therapeutic mechanism for anal eczema while highlighting its potential as an effective treatment approach for this debilitating condition.

Introduction

Anal eczema is an allergic skin condition that affects the perianal region and mucosa, exhibiting various clinical manifestations¹. The characteristic symptoms include anal erythema, papules, blisters, erosion, exudates, and crusting. These symptoms mostly arise due to scratching, thickening, and roughness of the affected area².

Anal eczema, characterized by a prolonged duration of the disease, recurrent attacks, and challenging treatment, can have adverse effects on patients' physical and mental health³. The pathogenesis of anal eczema is not yet clear, and modern ....

Protocol

This study does not refer to ethical approval and consent to participate. The data used in this study was obtained from gene databases.

1. Prediction of disease targets

1. Access the GeneCards database (https://www.genecards.org) and online Mendelian inheritance in man database (OMIM, https://www.omim.org), utilizing "anus eczema" as the search term for disease targets.
2. Download the spreadsheets of the disease targets. Delete the repeated targets to .......

Discussion

Atopic dermatitis is a specific form of eczema that shares underlying mechanisms with eczema. Hub genes believed to be related to this condition are TNF, MAPK14, and CASP3. The therapeutic effects of SDG on anal eczema are mainly attributed to its action on the TNF and MAPK signaling pathways via these three hub genes¹⁷.

SDG includes five distinct drugs: indigo naturalis, golden cypress, calcined gypsum, calamine, and Chinese Gall. In traditional Chinese medicine, calci.......

Materials

Name	Company	Catalog Number	Comments
AutoDockTools	AutoDock	https://autodocksuite.scripps.edu/adt/
Cytoscape 3.9.1	Cytoscape	https://cytoscape.org/
GeneCards database	GeneCards	https://www.genecards.org
GEO database	National Center for Biotechnology Information	https://www.ncbi.nlm.nih.gov/geo/
GEO2R tool	National Center for Biotechnology Information	https://ncbi.nlm.nih.gov/geo/geo2r/
Metascape	Metascape	https://metascape.org/
Online Mendelian inheritance in man database	OMIM	https://www.omim.org
RCSB protein database	RCSB Protein Data Bank (RCSB PDB)	http://www.pdb.org/
STRING database	STRING	https://string-db.org/
Swiss ADME database	Swiss Institute of Bioinformatics	http://www.swissadme.ch/index.php
Traditional Chinese Medicine system's pharmacology database (TCMSP)	Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform	http://tcmspw.com/tcmsp.php
Venny2.1	BioinfoGP	https://bioinfogp.cnb.csic.es/tools/venny/index.html