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Integrative Network Analysis of Bioactive Compounds from Punica granatum L. Peel: Multi-Target Mechanisms in Wound
Seyyed Shahab Shokri1, Ebrahim Salimi Sabour2, Seyed Morteza Hosseini3
1Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Background:
Wound-healing agents often have limited efficacy and require prolonged recovery times, prompting growing interest in developing herbal-based formulations. Among these, Punica granatum L. has attracted considerable attention because of its high polyphenolic content. Despite its widespread use, the precise pharmacological targets underlying its wound-healing effects remain poorly understood and require systematic investigation.
Objectives:
This study aimed to elucidate the underlying pharmacological mechanisms of the topical wound-healing properties of P. granatum L. using a network pharmacology approach.
Methods:
Bioactive compounds of P. granatum L. and their potential target genes were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Similarity Ensemble Approach (SEA), and SwissTargetPrediction databases. Wound healing-related genes were retrieved from the GeneCards database. Genes intersecting P. granatum L. targets and wound healing-associated genes were subjected to functional enrichment analyses, including protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The PPI network was further analyzed using Cytoscape, and the phytoconstituent-target interaction network was visualized using Gephi. These findings were validated using molecular docking.
Results:
A total of 40 intersecting genes were identified as potential P. granatum L. targets involved in wound healing. Among these, EGFR, PTPN11, HRAS, IGF1R, and ESR1 were identified as key hub genes. Functional enrichment analysis indicated that the most significantly enriched signaling pathways included the MAPK, PI3K-Akt, EGFR tyrosine kinase inhibitor resistance, focal adhesion, and FoxO signaling pathways. Molecular docking analysis confirmed favorable binding of quercetin and ellagic acid to the hub targets EGFR, IGF1R, and ESR1.
Conclusions:
These findings elucidate the pharmacological pathways underlying P. granatum-mediated wound healing and suggest that P. granatum L. acts as a multi-target modulator in the wound-healing process.
