Network Pharmacology Analysis of Piper guineense-Derived Phytochemical Compounds for Wound Healing Activity

Piper guineense, a West African spice and medicinal plant, is traditionally employed for wound healing, yet the molecular mechanisms underlying its therapeutic activity remain poorly defined. This study aimed to elucidate the wound‑healing potential of P. guineense phytochemicals using a network pharmacology approach. The drug-likeness properties and predicted targets of reported phytochemicals were assessed via SwissADME. Differentially expressed genes (DEGs) associated with wound pathogenesis were retrieved from the Gene Expression Omnibus, and overlapping genes were identified using the Bioinformatic and Evolutionary Genomics Venn diagram. Protein–protein interaction (PPI) networks were constructed with STRING and analyzed in Cytoscape. Functional enrichment and KEGG pathway analyses were performed using ShinyGO. Of 211 identified compounds including fatty acid esters, terpenoids, phenolics, benzodioxoles, lactones, and alkaloid‑like molecules, 210 exhibited drug‑like properties. These were linked to 1153 genes, of which 248 overlapped with 10,300 wound‑related DEGs. The PPI network revealed dense interconnections (248 nodes, 1618 edges, average node degree 13, clustering coefficient 0.479, enrichment p < 1.0e⁻¹⁶). Gene enrichment highlighted five hub genes: PTGS2, GSK3B, HSP90AA1, EGFR, and GAPDH. These targets regulate inflammation, proliferation, migration, protein folding, stress response, and energy metabolism. Several compounds were predicted to interact with PTGS2, GSK3B, HSP90AA1, and EGFR, supporting coordinated multi‑target actions. In conclusion, P. guineense demonstrates wound‑healing potential through synergistic regulation of inflammation, angiogenesis, re‑epithelialization, and tissue remodeling. This study underscores the utility of network pharmacology in bridging traditional medicine with modern molecular insights.