Phytochemical Profiling and Computational Screening of Musa acuminata Peel as Hemorrhagic Wound Treatment Candidate: Network Pharmacology, Molecular Docking, Molecular Dynamics, and DFT Approaches.

Background

Hemorrhagic wounds pose significant clinical challenges, with approximately 20% associated with surgical site infections and an increased mortality risk. Despite growing interest in natural product-based medicines, the molecular targets and bioactive phytochemicals of Musa acuminata peel relevant to hemorrhagic wound healing are insufficiently established.

Methods

This study employed an integrative in silico approach to identify bioactive phytochemicals from the ethyl acetate extract of Musa acuminata peel as potential wound healing agents. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) profiling was performed for phytochemical characterization, followed by drug-likeness and toxicity screening via OSIRIS DataWarrior. Network pharmacology, molecular docking, molecular dynamics (MD), binding free energy calculation, pharmacokinetic properties prediction, and density functional theory (DFT) analysis were subsequently conducted.

Results

LC-HRMS profiling identified 211 compounds across 21 chemical classes, of which 18 met drug-likeness criteria. Network pharmacology revealed five key protein targets. Molecular docking demonstrated that Compound 16 (-9.34 kcal/mol) and Compound 17 (-9.26 kcal/mol) exhibited stronger binding affinity toward VEGFR2 than Axitinib (-9.15 kcal/mol), with key interactions at glutamic acid-917 (GLU917) and cysteine-919 (CYS919). MD simulations over 100 ns confirmed complex stability, with BP16 showing superior binding stability and favorable MM/PBSA free energy. Pharmacokinetics and DFT analysis further supported BP16 as the most promising lead compound, exhibiting favorable pharmacokinetic properties, low predicted toxicity, and enhanced electronic stability.

Conclusions

BP16 and BP17 are identified as potential VEGFR2-targeting candidates, providing a rational mechanistic foundation for future experimental validation as natural hemorrhagic wound healing therapeutics.