Objectives: Melanogenesis is a complex biogenesis involving a synthesis pathway combined with the maturation and transport of melanin inside melanosomes. Kojic acid (KA) is one of the most well-known anti-melanogenesis agents, used to treat hyperpigmentation by inhibiting the tyrosinase enzyme in the melanin synthesis pathway. However, the molecular targets and their molecular cascade have not been fully identified and explained yet. This study is designed to identify KA’s molecular targets and its molecular cascade for inhibiting melanogenesis in the skin.

Methodology: Genes related to pigmentation and melanogenesis in the skin, as well as genes affected by KA were collected from various databases. The Venn diagram result of these genes was further utilized to construct a protein-protein interaction network and gene clustering. The interaction between KA and TYR, as well as STAT5A were modeled using molecular docking using AutoDock.

Results: A total of 15 proteins were identified as the targets of KA. During KA treatment, the identified proteins work together in a coordinated manner to support its anti-melanogenesis activity.

Conclusion: This orchestrated action of KA on various protein targets leads to the inhibition of melanin synthesis and ultimately helps in reducing hyperpigmentation and brightening the skin tone.