Pentapeptide-18 as an anti-aging candidate: Spectroscopic characterization and molecular interaction analysis

Skin aging is predominantly associated with the progressive breakdown of the dermal extracellular matrix (ECM), leading to visible manifestations such as wrinkle development caused by repetitive facial muscle movements and a gradual reduction in collagen and elastin synthesis. This degeneration is intensified by external factors including ultraviolet exposure, tobacco use, and nutritional imbalance, which interfere with major intracellular signaling pathways-namely TGF-β, TNF-α, MAPK, PI3K/AKT, and NF-κB-that collectively regulate inflammatory responses, oxidative stress, and ECM remodeling. Pentapeptide-18 (Leuphasyl®), a bioactive peptide known for its neuromodulatory properties, has demonstrated the ability to mitigate wrinkle formation by inhibiting neurotransmitter release, while simultaneously improving skin hydration, elasticity, and texture. In this study, the anti-aging activity of Pentapeptide-18 was comprehensively examined through a combination of experimental analyses and computational modeling. Structural optimization and electronic property evaluation were performed using density functional theory (DFT) calculations with the 6-31 + +G(d,p) basis set, complemented by frontier molecular orbital (HOMO-LUMO) and molecular electrostatic potential (MEP) analyses. Theoretical vibrational frequencies were assigned via potential energy distribution (PED) analysis and validated experimentally using FTIR, ATR-FTIR, and Raman spectroscopy. Additionally, molecular docking and molecular dynamics simulations were employed to investigate the binding behavior of Pentapeptide-18 with key molecular targets implicated in skin aging, including TGF-β, TNF-α, MAPK, PI3K/AKT, and NF-κB. Pharmacokinetic and drug-likeness properties were further assessed through ADMET (absorption, distribution, metabolism, excretion, and toxicity). The collective findings provide mechanistic insight into the molecular interactions and stability of Pentapeptide-18, reinforcing its potential as a safe, effective, and non-invasive candidate for advanced anti-aging skin care applications.