Abstract
Scalp itch and beard irritation are multifactorial neurocutaneous disorders associated with microbial dysbiosis, impaired skin barrier function, inflammation, and activation of the transient receptor potential vanilloid 1 (TRPV1) ion channel, a key mediator of itch signalling and neurogenic inflammation. Although conventional therapies such as ketoconazole, zinc pyrithione, and hydrocortisone provide symptomatic relief, their long-term use is limited by adverse effects, irritation, and regulatory concerns, highlighting the need for safer steroid-free alternatives. In the present study, the molecular mechanism underlying the antipruritic potential of FERMENZA, a natural postbiotic formulation, was investigated using an integrated computational approach. LC-MS metabolite profiling identified major phytochemicals, which were subjected to molecular docking against the TRPV1 vanilloid-binding pocket, followed by 40 ns molecular dynamics simulations in a POPC lipid bilayer under physiological conditions. Among the identified metabolites, rutin exhibited the highest binding affinity (-12.76 kcal mol-1), followed by ellagic acid (-11.83 kcal mol-1), outperforming the reference antagonist capsazepine (-8.96 kcal mol-1) as well as hydrocortisone (-8.06 kcal mol-1), ketoconazole (-6.56 kcal mol-1), and zinc pyrithione (-6.06 kcal mol-1). Both phytochemicals formed stable hydrogen bonds and hydrophobic interactions with key residues in the TRPV1 binding pocket. Molecular dynamics simulations confirmed stable protein-ligand complexes without ligand dissociation throughout the simulation. Rutin showed the highest structural stability, reflected by the lowest backbone RMSD (3.72 ± 0.37 Å), stable radius of gyration, minimal solvent-accessible surface area fluctuations, and negligible perturbation of the surrounding POPC membrane. Overall, the findings identify rutin, followed by ellagic acid, as promising natural TRPV1 modulators and provide a molecular basis for the antipruritic activity of FERMENZA, supporting its potential as a safe, drug-free and steroid-free natural formulation for managing scalp itch and beard hypersensitivity.