Network Pharmacology of Theaflavin in Wound Healing via EGFR Pathway

Abstract

Introduction: Tea is used by humans for hydration, stress relief, and improved focus, and its consumption is linked to numerous health benefits such as supporting heart health, cardiovascular diseases ,boosting the immune system, aiding digestion etc.These benefits come from the rich antioxidants and anti-inflammatory compounds, such as flavonoids, found in tea. Theaflavin, a polyphenolic compound derived from black tea, exhibits potent regenerative and anti-inflammatory properties. This study utilized a network pharmacology approach to investigate its role in modulating the EGFR pathway during wound healing. Methods: Potential targets of Theaflavin were identified using Swiss Target Prediction. These targets were then cross-referenced with EGFR pathway-related genes obtained from the GeneCards and OMIM databases. Overlapping targets were visualized using a Venn diagram. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using ShinyGO 8.0 to identify relevant biological functions and signaling pathways. Protein-protein interaction (PPI) networks were constructed via the STRING database and visualized using Cytoscape software. Key hub genes within the PPI network were identified using the CytoHubba plugin.For experimental validation, human periodontal ligament (PDL) cells were treated with 20 μM Theaflavin for 24 hours to assess gene expression changes. Results: Bioinformatics analysis revealed several overlapping targets between Theaflavin and the EGFR pathway. GO and KEGG enrichment analyses indicated significant involvement in pathways related to cell proliferation, wound healing, and signal transduction. PPI network analysis identified multiple hub genes potentially regulated by Theaflavin. In vitro experiments in PDL cells demonstrated that treatment with Theaflavin led to the upregulation of key EGFR pathway components and genes associated with tissue regeneration and wound healing. Conclusion: Theaflavin may exert regenerative effects by modulating the EGFR signaling pathway and enhancing the expression of wound healing-related genes. These findings suggest that Theaflavin holds therapeutic potential for promoting tissue repair, particularly in periodontal applications.