multi-target mechanism of polyherbal extract to treat diabetic foot ulcer based on network pharmacology and molecular docking

Introduction: diabetic foot ulcer (dfu) potentially leads to loss of function, infections, hospitalization, lower-extremity amputation, and even death. the potential therapeutic efficacy of a polyherbal candidate named tip-heal was identified for treating dfu. tip-heal, which stands for tinospora crispa, isotoma longiflora, and piper betle l var nigra, consists of extracts from these three herbs in a ratio of 2:1:1. the indonesian population commonly uses these herbs due to their wound-healing properties. it is our interest to analyse the mechanism of the polyherbal extract using network pharmacology and molecular docking. methods: this study uses network pharmacology and molecular docking methods to analyze the multi-target mechanism of active compounds in tip-heal extract for dfu treatment. the proteins targeted by the bioactive chemical present in tip-heal and dfu were identified within a particular dataset with the keyword homo sapiens. the identified target proteins were assessed using gene ontology (go) analysis, the kyoto encyclopaedia of gene and genomes (kegg) pathways, protein-protein interactions (ppis), and molecular docking. results: the critical proteins obtained were akt serine/threonine kinase 1 (akt1), caspase-3 (casp3), epidermal growth factor receptor (egfr), proto-oncogene tyrosine-protein kinase src (src) and matrix metalloproteinase-9 (mmp-9). several compounds, namely pubchem (compound identifier=cid: 5319898), 3-epiursolic acid, palmitic acid, and alpha-linolenic acid showed great potential as viable candidates to facilitate the healing process of dfu. conclusion: the findings of this study indicate that the tip-heal extract has the potential to be used as a natural herbal treatment for dfus with the involvement of akt1, casp3, efgr, and src proteins.