J. Pharm. Pharmacogn. Res., vol. 14, no. 1, Article ID 2475, Jan-Feb 2026.

DOI: https://doi.org/10.56499/jppres_14.1.2475

Original Article

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

[Eficacia como inhibidor de la tirosinasa de compuestos activos de Centella asiatica (L.) Urb., ácido etilascórbico y coenzima Q10 para el blanqueamiento de la piel mediante la evaluación in silico]

Ni L. D. Aryani¹, Dini Kesuma^2*, Armiza D. Yasinta¹, Elya Andreyana²

¹Department of Pharmaceutics, Faculty of Pharmacy, University of Surabaya, Surabaya, Indonesia.

²Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Surabaya, Surabaya, Indonesia.

*E-mail: dinikesuma@gmail.com, dini_kesuma@staff.ubaya.ac.id

Abstract

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.

Keywords: Centella asitica; molecular docking; molecular dynamics; hyperpigmentation; tyrosinase.

Resumen

Contexto: La hiperpigmentación y el melasma a menudo se tratan con cremas tópicas a base de hidroquinona. A pesar de su eficacia, el uso de hidroquinona está limitado por la irritación, la fotosensibilidad y la sensibilidad a la oxidación, lo que hace que la aplicación a largo plazo resulte desfavorable.

Objetivos: Explorar los fitoquímicos de Centella asiática como alternativas naturales en formulaciones tópicas, en combinación con agentes químicos oxidativos como el ácido etil ascórbico y la coenzima Q10, mediante evaluación preliminar in silico.

Métodos: Se realizaron simulaciones de acoplamiento molecular y dinámica molecular de ácido asiático, ácido madecásico, asiaticósido y madecasósido de C. asiatica, junto con ácido etilascórbico y coenzima Q10, contra la enzima tirosinasa (PDB: 5I3A). El acoplamiento se realizó con Molegro Virtual Docker (Molexus v7) y las simulaciones de dinámica molecular se realizaron en Maestro (Schrödinger) durante 100 ns.

Resultados: El ácido asiático exhibió la actividad más prometedora, con una afinidad de unión comparable a la de la hidroquinona y interacciones estables durante simulaciones de 100 ns (RMSD promedio de ~3 Å). Los derivados de glucósidos (asiaticósido y madecasósido) mostraron una unión débil e inestable. En particular, el ácido 3-o-etilascórbico demostró una energía de unión más alta y una estabilidad superior (RMSD promedio de 2,971 Å) que la hidroquinona, mientras que la coenzima Q10 mostró una energía libre de unión positiva y una estabilidad deficiente.

Conclusiones: Los hallazgos sugieren que el ácido asiático es el compuesto antihiperpigmentación más activo en C. asiatica, mientras que los glucósidos carecen de actividad inhibidora de la tirosinasa. La incorporación de ácido 3-o-etilascórbico, en lugar de la coenzima Q10, podría mejorar la eficacia de las formulaciones tópicas basadas en C. asiatica para el tratamiento de la hiperpigmentación.

Palabras Clave: acoplamiento molecular; Centella asiática; dinámica molecular; hiperpigmentación; tirosinasa.

 

https://jppres.com/jppres/pdf/vol14/jppres_14.1.2475.pdf

 

 

Citation Format: Aryani NLD, Kesuma D, Yasinta AD, Andreyana E (2026) 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. J Pharm Pharmacogn Res 14(1): 2475. https://doi.org/10.56499/jppres_14.1.2475

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