In-Silico Insights Into Phenolic Compounds from Stingless Bee Honey as Wound Healing Agents Via TGF-β1 Modulation

Wound healing is a complex cellular process regulated by Transforming Growth Factor Beta 1 (TGF-β1), which stimulates extracellular matrix (ECM) production, fibroblast migration, and differentiation into myofibroblasts. Despite this, the influence of phenolic compounds from stingless bee honey (SBH) on TGF-β1-mediated wound repair remains poorly understood, highlighting the need for systematic investigation. The objective of this study was to identify potential wound-healing agents targeting TGF-β1 (PDB ID: 6B8Y) from SBH phenolics. To achieve this, we employed an integrative in-silico approach comprising molecular docking, pharmacokinetic profiling, and molecular dynamics (MD) simulations. The binding affinities of the compounds ranged from − 6.0 to -9.9 kcal/mol, whereas the control compound (Nitrofurazone) exhibited a binding affinity of -6.6 kcal/mol. Based on the ADMET analysis, Naringenin and Pinocembrin showed the best modulatory profiles. These two compounds complex with TGF-β1 (PDB ID: 6B8Y) were then subjected to MD simulation, and both compounds were in a stable structure compared to the control compound, as demonstrated by MD simulation and PCA analysis. Furthermore, the binding free energy analyses revealed that Naringenin and Pinocembrin exhibited comparable binding free energies of -27.09 and − 14.11 kcal/mol, respectively. In contrast, the control compound showed a binding free energy of -15.85 kcal/mol. Furthermore, network pharmacology analysis of Naringenin and Pinocembrin in wound healing revealed their involvement in multiple signaling pathways and key target proteins, including the PI3K-Akt signaling pathway and HIF-1 signaling pathway, which is associated with anti-inflammatory, antioxidant, and tissue regenerative (wound healing) effects. In line with the study’s objective of exploring SBH phenolics as modulators of TGF-β1, our findings suggest that Naringenin and Pinocembrin hold promise as wound-healing agents. However, further in-vitro and in-vivo validation is required to establish their biological relevance and therapeutic potential.