Melanin is a skin pigment that plays an important role in protection from the harmful effects caused by ultraviolet (UV) light. Overproduction and accumulation of melanin can result in pigmented patches and skin discolorations, such as chloasma, solar lentigo and freckles, that lead to perceived esthetic problems [1, 2]. The production of melanin pigment, also called "melanogenesis, " is a complicated process regulated by various melanogenesis enzymes, such as tyrosinase, and tyrosinase-related protein 1 (TYRP1) and TYRP2. Among these enzymes, tyrosinase is the essential enzyme in melanogenesis. It catalyzes two initial steps in this process; namely hydroxylation of L-tyrosine into 3,4-dihydroxyphenylalanine (L-DOPA) and the oxidation of L-DOPA into dopaquinone. These melanogenesis enzymes are regulated by microphthalmia-associated transcription factor (MITF) [3-5]. In addition, melanogenesis is modulated by mitogen-activated protein kinase (MAPK) signaling via extracellular signal-regulated kinases (ERK) and p38 MAPK. The phosphorylation of ERK (Thr202/Tyr204) and p38 (Thr180/Tyr182) leads to MITF degradation, which plays a pivotal role in suppressing melanin production [6-8]. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is also known to be involved in the regulation of melanogenesis, where the phosphorylation of Akt leads to negative regulation of melanogenesis [9, 10]. Additionally, UV light radiation causes the synthesis of reactive oxygen species (ROS) that are also involved in the regulation of melanin synthesis. Hence, ROS scavengers and inhibitors of ROS generation may down-regulate melanogenesis [11]. Currently, known depigmenting agents, such as kojic acid, arbutin and linoleic acid, are used as cosmetic agents Melanin is a major factor that darkens skin color as one of the defense systems to prevent the harmful effects of UV light. However, darkened skin from the localized or systemic accumulation of melanin is viewed in many cultures as an esthetic problem. Consequentially, searching for antimelanogenic agents from natural sources is very popular worldwide. Previous screening of fermented rice products, obtained from various rice cultivars fermented with different sources of loog-pang (Thai traditional fermentation starter), revealed that the highest ability to reduce the melanin content in B16F10 melanoma cells was from unpolished black rice fermented with a defined starter mixture of microbes isolated from loog-pang E11. The aim of this study was to investigate the mechanism of the fermented unpolished black rice (FUBR) on the inhibition of melanogenesis in B16F10 melanoma cells. The strongest reduction of cellular melanin content was found in the FUBR sap (FUBRS). The melanin reduction activity was consistent with the significant decrease in the intracellular tyrosinase activity. The FUBRS showed no cytotoxic effect to B16F10 melanoma or Hs68 human fibroblast cell lines. It also significantly reduced the transcript and protein expression levels of tyrosinase, tyrosinase-related pr...