Abstract
The essential function of melanin is to protect our skin against harmful environmental factors. However, excessive melanin production can cause undesirable hyperpigmentation issues, such as freckles and melasma. Although several compounds are used to control melanin production by inhibiting tyrosinase (TYR), their efficacy is limited by skin-related adverse effects and cytotoxicity concerns. Consequently, searching for new natural compounds with an effective TYR inhibitor (TYR-I) activity but less harmful effects continues. Plant-based natural extracts are an alternative that are in great demand due to their safety and diverse biological properties. This study assessed ten isolated plant compounds for their TYR-I activities using an in vitro mushroom TYR inhibition assay. Among these compounds, piperine (400 μM) demonstrated the highest TYR-I activity, with a potency of 36.27 ± 1.96 %. Hence, this study examined the effect of piperine on melanogenesis in melanocyte stimulating hormone-treated B16F10 melanoma cells and using kojic acid as a positive reference. Cell viability was evaluated through the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Measurements of cellular TYR activity and melanin content were performed and related to changes in the transcriptional expression levels of melanogenesis-related genes, assessed via quantitative real-time reverse transcriptase (RT-q)PCR analysis. The results revealed that piperine at a concentration of 44 μM significantly reduced cellular TYR activity by 21.51 ± 2.00 % without causing cytotoxicity. Additionally, at the same concentration, piperine significantly decreased the intracellular melanin content by 37.52 ± 2.53 % through downregulating transcription levels of TYR and TYR-related protein 1 (TRP-1) but not TRP-2. Kojic acid, at a concentration of 1407 μM, induced a significant decrease in the melanin content and cellular TYR activity by suppressing all three melanogenesis-related genes. These findings suggest that piperine has potential as a potent depigmenting agent.