In silico discovery of skin depigmenting agents from Chlorella vulgaris: a network pharmacology and molecular simulation approach

Hyperpigmentation is a common skin condition resulting from uncontrolled melanin production or accumulation. Commercial skin-whitening products have been reported to cause undesirable skin effects, limiting safe treatment options. Microalgae are increasingly explored as sustainable sources for cosmetic applications due to their diverse bioactive properties and versatility. Chlorella vulgaris, a green microalga, is regarded as a promising source of beneficial compounds, particularly in cosmeceuticals. In this study, pigmentation-related targets were identified from public databases, and network pharmacology techniques were employed, including protein–protein interaction (PPI) network construction using STRING and visualization in Cytoscape. Enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The interactions between hub targets and C. vulgaris compounds retrieved from PubChem were investigated via molecular docking and molecular dynamics simulations. Hub genes TYRP1, TYR, TP53, SLC45A2, CTNNB1, and MC1R were identified as significant regulators of melanocyte differentiation and melanogenesis-associated pathways. Molecular docking highlighted four hit compounds namely 7,22-ergostadienol acetate (CID: 14056082), dehydroergosterol acetate (CID: 69827569), ergosterol acetate (CID: 6436903), and [(3S,10S,13 R,14 R,17 R)-17-[(E,2 R,5 R)-5-ethyl-6-methylhept-3-en-2-yl]-10,13-dimethyl 2,3,4,12,14,15,16,17-octahydro-1 H-cyclopenta[a]phenanthren-3-yl] acetate (PubChem CID: 162856537), which showed favourable binding affinities with the core gene targets. Molecular dynamics revealed that these compounds could bind stably to SLC45A2, CTNNB1, and MC1R, suggesting potential depigmenting effects of C. vulgaris. While these findings provide a theoretical framework for microalgae-derived depigmentation agents, the study is based solely on in silico predictions and relies on currently available compound–target databases, which may not encompass the full chemical diversity of C. vulgaris. Therefore, further validation through phytochemical characterization, in vitro assays, and in vivo studies is essential to confirm the therapeutic potential of these compounds for pigmentation-related skin disorders.