Calebin-A, a Curcuminoid Analog Inhibits α-MSH-Induced Melanogenesis in B16F10 Mouse Melanoma Cells

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 a-melanocyte stimulating hormone (alpha MSH)-stimulated melanogenesis in B16F10 mouse melanoma cells. Our results showed that CBA (20 mu M) significantly suppressed alpha MSH-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 alpha-glucosidase activity but significantly inhibited direct alpha-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.