Glabridin is one of the best-known bioactive compounds found in licorice (Glycyrrhiza glabra). It has been studied for its effects on pigmentation for decades, although the way it influences melanogenesis appears to be more complicated than simply blocking tyrosinase.
Melanin production is controlled by a network of signals inside melanocytes. One important route begins when melanocortin signals, including α-MSH, activate MC1R on the melanocyte surface. This increases intracellular cAMP and activates protein kinase A (PKA). Further downstream, CREB and the transcription factor MITF help regulate genes involved in pigment synthesis, including TYR, TYRP1 and DCT/TYRP2.
Early studies of glabridin mainly focused on tyrosinase. Experiments in cultured melanoma cells showed that glabridin could reduce tyrosinase activity and melanin formation. More recent work suggests that its activity may extend further upstream and affect the regulatory machinery that determines how much of these melanogenic proteins the cell produces in the first place.
One particularly interesting target is the CREB–CRTC1–MITF axis.
CRTC1 is a transcriptional coactivator. When it enters the nucleus, it can cooperate with CREB and enhance transcription of MITF. MITF then promotes the expression of several proteins required for melanogenesis. A 2025 study investigating licorice-derived compounds found that glabridin reduced CREB phosphorylation and restricted the nuclear translocation of CRTC1. More phosphorylated CRTC1 remained in the cytoplasm, leaving less available to participate in MITF transcription.
The downstream effect was a reduction in MITF-associated melanogenic proteins and melanin accumulation.
This is worth distinguishing from direct tyrosinase inhibition. Rather than acting only on an enzyme that is already present, glabridin appears capable of influencing signaling and transcriptional events that determine melanogenic activity more broadly.
The picture is becoming even more complex. Recent experiments in human melanoma cells have also linked glabridin to reduced Wnt/β-catenin signaling, another pathway capable of regulating MITF. Other findings suggest that glabridin may affect melanocyte dendrite formation and the subsequent transfer of melanin toward keratinocytes. These mechanisms are still being investigated and should not be treated as equally established in normal human skin.
So it may be more accurate to think of glabridin as a multi-target regulator of pigmentation rather than simply a tyrosinase inhibitor.
That distinction also matters when interpreting cosmetic claims. Much of the mechanistic evidence comes from cultured melanoma cells, animal experiments, or controlled laboratory models. These studies help explain how glabridin may work, but they do not mean that every molecular effect will occur to the same extent when glabridin is applied topically to human skin.
What the available evidence does suggest is that glabridin can interfere with melanogenesis at several levels-from tyrosinase activity to MITF-related transcriptional regulation. That broader biological profile is one reason the compound continues to attract attention in pigmentation and skin-tone research.