Exploring the wound healing efficacy of Kyllinga nemoralis: Phytochemical analysis, network pharmacology, molecular docking, and molecular dynamics simulations

Kyllinga nemoralis (K. nemoralis) has traditionally been employed for its therapeutic properties, particularly in wound healing; however, the underlying molecular mechanisms remain insufficiently understood. This study investigates the wound-healing potential of the methanolic extract of K. nemoralis using an integrative in-silico framework encompassing phytochemical profiling, network pharmacology, molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized born surface area (MM/GBSA) binding free energy analysis. Gas chromatography-mass spectrometry (GC-MS) analysis identified 70 phytochemical constituents, of which 20 were major compounds. Network pharmacology analysis revealed 24 hub genes associated with wound-healing-related pathways, with toll-like receptor 4 (TLR4) emerging as a key regulatory target based on its topological importance within the protein-protein interaction network. Molecular docking was employed to explore plausible binding modes of selected phytochemicals within the TLR4 binding pocket. The stability and dynamic behavior of the resulting ligand-protein complexes were subsequently evaluated using MD simulations, including principal component analysis (PCA), free energy landscape (FEL), and dynamic cross-correlation matrix (DCCM) analyses. Importantly, MM/GBSA binding free energy calculations demonstrated thermodynamically favorable interactions, with β-sitosterol and α-selinene exhibiting stable and energetically favorable ΔGbinding values toward TLR4. Collectively, these findings suggest that β-sitosterol and α-selinene may contribute to the wound-healing potential of K. nemoralis through modulation of key molecular targets such as TLR4. This study provides a robust molecular framework to support future experimental validation and therapeutic exploration of K. nemoralis in wound management.