Studi In Silico Senyawa Bioaktif Bawang Dayak (Eleutherine bulbosa) Sebagai Inhibitor Mmp-1 Untuk Potensi Anti-Aging Kulit

Abstract

Skin aging is closely associated with increased activity of Matrix Metalloproteinase-1 (MMP-1), an enzyme responsible for collagen degradation, leading to reduced skin elasticity and wrinkle formation. Eleutherine bulbosa (Bawang Dayak) contains various bioactive compounds with potential anti-aging properties. This study evaluated the potential of bioactive compounds from E. bulbosa as MMP-1 inhibitors using an in silico approach. A total of 18 bioactive compounds from E. bulbosa were screened alongside one native ligand as a reference. Sequential filtering was applied, beginning with Lipinski’s Rule of Five, which retained 13 compounds for Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) evaluation, particularly focusing on topical application parameters, including skin sensitization and permeability. Subsequently, six shortlisted compounds that met safety and topical criteria were evaluated through molecular docking analysis against the MMP-1 target protein. Oxyresveratrol exhibited a more negative docking score than the native ligand, with a binding free energy (ΔG) of −9.40 kcal/mol and an estimated inhibition constant (Ki) of 129.59 nM, compared with −8.93 kcal/mol and 284.97 nM, respectively, for the native ligand. Oxyresveratrol fulfilled drug-likeness criteria, demonstrated favorable predicted skin permeability, and showed no predicted skin-sensitization, hepatotoxic, mutagenic, or carcinogenic risks. It also formed key interactions with MMP-1 active-site residues. Isoliquiritigenin showed similarly favorable binding affinity (ΔG = −9.22 kcal/mol) with a sound safety profile. Overall, oxyresveratrol demonstrated the most favorable binding affinity toward MMP-1 among the evaluated compounds. Further in vitro and in vivo studies are required to validate its inhibitory activity and potential application in topical anti-aging skincare development.