Abstract
Hyperpigmentation skin disorders comprise melasma, age spots, and post-inflammatory hyperpigmentation. They are characterized by an aberrant upregulation of melanin pigment and pose a significant burden aesthetically. Calebin-A (CBA) is a natural curcuminoid analog derived from turmeric root (Curcuma longa) but, unlike curcumin, it has not been explored yet for anti-melanogenic activity. Hence, in the current study, we studied CBA for its effects on α-melanocyte stimulating hormone (αMSH)-stimulated melanogenesis in B16F10 mouse melanoma cells. Our results showed that CBA (20 μM) significantly suppressed αMSH-stimulated melanogenesis after 48 h treatment. The underlying mechanisms of CBA’s anti-melanogenic activity were studied, and it was shown that CBA did not affect either intracellular tyrosinase activity or the direct activity of tyrosinase enzyme. Additionally, CBA did not affect intracellular α-glucosidase activity but significantly inhibited direct α-glucosidase activity. CBA also directly scavenged 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals, consistent with potent antioxidant activity but did not inhibit intracellular reactive oxygen species (ROS). CBA increased acidification of cellular organelles and inhibited maturation of melanosomes by significantly reducing the number of mature melanosomes. Our results indicate that CBA may hold promise as a pigmentation inhibitor for hyperpigmentation disorders for cosmetic use by targeting pathways other than tyrosinase inhibition. Further studies to delineate the molecular signaling mechanism of melanogenesis inhibition and test anti-melanogenesis efficacy of CBA in human skin melanocytes and skin equivalents are warranted.
Highlights
Hyperpigmentation is caused by excessive production of melanin pigment in skin melanocytes and is associated with dermatological disorders such as lentigo senilis (LS), melasma, and post-inflammatory hyperpigmentation (PIH), which affect the individuals aesthetically
The secretion of α-melanocyte stimulating hormone (αMSH) from keratinocytes is triggered upon exposure to ultraviolet radiation (UVR) [4] which leads to upregulation of the expression of the αMSH receptor on melanocytes [5]
In order to test if CBA may inhibit the α-glucosidase enzyme which regulates the early stage of maturation of tyrosinase enzyme in cells [21,22], lysates of B16F10 cells were assayed for enzyme activity by addition of pNG substrate and the rate of formation of the reaction product p-nitrophenol was monitored at 405 nm in kinetic mode for 30 min at 37 ◦ C in a microplate reader
Summary
Hyperpigmentation is caused by excessive production of melanin pigment in skin melanocytes and is associated with dermatological disorders such as lentigo senilis (LS), melasma, and post-inflammatory hyperpigmentation (PIH), which affect the individuals aesthetically. The secretion of αMSH from keratinocytes is triggered upon exposure to ultraviolet radiation (UVR) [4] which leads to upregulation of the expression of the αMSH receptor on melanocytes [5]. Commercial tyrosinase inhibitors, such as kojic acid (KA), hydroquinone, and arbutin exhibit serious side-effects. CBA has shown superior biological activities as compared to curcumin in a limited number of studies: for example, CBA inhibited growth of human hepatoma HepG2 cells more potently than curcumin [17] and in another study, CBA showed superior protective effects on PC-12 cells in a β-amyloid toxicity model [9]. In this work, we studied the effects of CBA on αMSH-stimulated melanogenesis using B16F10 mouse melanoma cells and delineated the mechanisms of inhibition of melanogenesis
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