In-silico screening of phytochemicals in Calotropis gigantea for anti-vitiligo activity by targeting tyrosinase enzyme

Vitiligo is a chronic skin disorder characterized by the loss of functionalized melanocytes, which causes depigmented areas. Current therapies have limited effectiveness, resulting in an increased interest in plant-based alternatives. This study focuses on the anti-vitiligo potential of Calotropis gigantea (Wara) using in-silico screening of its phytochemicals that target tyrosinase, a crucial enzyme in the production of melanin. A total of 43 phytocompounds were extracted from the IMPPAT 2.0 database and assessed using ADME and toxicity filters. Docking analyses were complemented with ADME results to evaluate absorption, distribution, metabolism, and excretion profiles, highlighting the potential of selected phytochemicals as viable therapeutic leads for vitiligo. The top nine options have been selected based on drug-likeness and safety profile. PyRx was used to perform molecular docking, which was then confirmed with Schrodinger to determine binding interactions with tyrosinase. The electrical characteristics and chemical reactivity of the lead compounds have been studied using Density Functional Theory (DFT). This study identifies beta-sitosterol and stigmasterol as promising enhancers for segmental vitiligo, and quercetin and flavylium as potential inhibitors/modulators for non-segmental vitiligo. It provides a mechanistic foundation for developing subtype-specific, plant-based therapeutic strategies for vitiligo and underscore the clinical relevance of dual-pathway tyrosinase modulation. These findings reveal that Calotropis gigantea has promising bioactive compounds for influencing melanogenesis, which supports its traditional usage in the treatment of vitiligo.