Inhibitory Effects of Pinostilbene Hydrate on Melanogenesis in B16F10 Melanoma Cells via ERK and p38 Signaling Pathways

Melanin protects our skin from harmful ultraviolet (UV) radiation. However, when produced in excess, it can cause hyperpigmentation disorders, such as melanoma, freckles, lentigo, and blotches. In this study, we investigated the effects of pinostilbene hydrate (PH) on melanogenesis. We also examined the underlying mechanisms of PH on melanin production in B16F10 cells. Our findings indicated that PH significantly inhibits melanin content and cellular tyrosinase activity in cells without causing cytotoxicity. In addition, Western blot analysis showed that PH downregulated the protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase, and other melanogenic enzymes, such as tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2). Although PH activated the phosphorylation of extracellular signal-regulated kinase (ERK), it inhibited p38 mitogen-activated protein kinases (p38). Furthermore, the inhibition of tyrosinase activity by PH was attenuated by treatment with PD98059 (a specific ERK inhibitor). Additionally, p-AKT was upregulated by PH treatment. Finally, the inhibitory effects of PH on melanin content and tyrosinase activity were confirmed in normal human melanocytes. These results suggest PH downregulates melanogenesis via the inhibition of MITF expression, followed by the MAPKase signaling pathways. Thus, PH may be used to treat or prevent hyperpigmentation disorders and in functional cosmetic agents for skin whitening.