Effectiveness as tyrosinase inhibitor from active compounds of Centella asiatica (L.) Urb., ethyl ascorbic acid, and coenzyme Q10 as skin whitening by in silico evaluation

Context: Hyperpigmentation and melasma are often treated with hydroquinone-based topical creams. Despite its effectiveness, hydroquinone use is limited by irritation, photosensitivity, and oxidation sensitivity, making long-term application unfavorable. Aims: To explore Centella asiatica phytochemicals as natural alternatives in topical formulations, in combination with oxidative chemical agents such as ethyl ascorbic acid and coenzyme Q10, through preliminary in silico evaluation. Methods: Molecular docking and molecular dynamics simulations were conducted on asiatic acid, madecassic acid, asiaticoside, and madecassoside from C. asiatica, along with ethyl ascorbic acid and coenzyme Q10, against the tyrosinase enzyme (PDB: 5I3A). Docking was performed using Molegro Virtual Docker (Molexus v7), and molecular dynamics simulations were carried out in Maestro (Schrödinger) for 100 ns. Results: Asiatic acid exhibited the most promising activity, with binding affinity comparable to hydroquinone and stable interactions during 100 ns simulations (average RMSD ~3 Å). Glycoside derivatives (asiaticoside and madecassoside) showed weak and unstable binding. Notably, 3-o-ethyl ascorbic acid demonstrated stronger binding energy and superior stability (average RMSD 2.971 Å) than hydroquinone, whereas coenzyme Q10 displayed positive binding free energy and poor stability. Conclusions: The findings suggest that asiatic acid is the most active anti-hyperpigmentation compound in C. asiatica, while glycosides lack tyrosinase inhibitory activity. Incorporation of 3-o-ethyl ascorbic acid, rather than coenzyme Q10, could enhance the efficacy of C. asiatica–based topical formulations for hyperpigmentation management.