Over the years, the cosmetic industry has shifted its focus from synthtic to natural compounds. This change is driven not only by the safety profile of natural ingredients but also by increased consumer awareness about the products they use. As a result, many natural skincare products have been launched in recent years. Hyperpigmentation disorders, such as melasma, age spots (solar lentigines), post-inflammatory hyperpigmentation, freckles, and acanthosis nigricans, are significant concerns. These conditions not only pose pathological issues but also affect individuals' self-esteem. Consequently, treating hyperpigmentation by reducing melanogenesis has become a key area of interest in cosmetology. Among various natural compounds, piceatannol (PCT) shows great potential in treating hyperpigmentation. The primary mechanism previously explored is the inhibition of the tyrosinase enzyme, which is one of the most researched strategies for combating melanogenesis. Additionally, PCT has been shown to downregulate MITF expression, a key gene responsible for the transcription of various melanogenic proteins and enzymes. However, beyond these two mechanisms, little is known about how PCT may inhibit melanogenesis. In this review, we aim to bridge that gap. We will explore and speculate on the possible upstream signaling pathways to MITF, such as Nrf, FOXO3a, CREB, MAPK signaling, etc., where PCT could potentially act to inhibit melanogenesis. This review will not only pave the way for future research related to PCT and hyperpigmentation but also highlight pathways that could be targeted for developing cosmetics and treatments for hyperpigmentation disorders.
Keywords: MITF; hyperpigmentation; piceatannol; skin; tyrosinase.
© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.