Depigmenting effect of Xanthohumol from hop extract in MNT-1 human melanoma cells and normal human melanocytes

Abstract

Xanthohumol (XH) is the most abundant prenylated flavonoid found in the hop plant ( Humulus lupulus L .) and has previously been shown to have depigmenting effects in B16F10 mouse melanoma cells; however, studies of its depigmenting efficacy in human melanocytes are still lacking. In this work, we explored the effects of XH on melanogenesis in MNT-1 human melanoma cells and normal human melanocytes from darkly-pigmented skin (HEM-DP). XH was screened for cytotoxicity over 48 h, and subsequently tested on melanogenesis in MNT-1 cells. XH was further tested in HEM-DP cells for melanin synthesis and melanosome export; dendricity was quantitated to assess effects on melanosome export. Melanosome degradation was studied in human keratinocytes (HaCaT). Our results showed that XH inhibited melanin synthesis in MNT-1 cells at 30 μM but increased intracellular tyrosinase activity without affecting ROS levels. In HEM-DP cells, XH robustly suppressed cellular tyrosinase activity at nontoxic concentrations (2.5–5 μM) without any effect on melanin synthesis. However, XH inhibited melanosome export by reducing dendrite number and total dendrite length. Further testing in HaCaT cells demonstrated that XH induced melanosome degradation at low micromolar concentrations without any cytotoxicity. In summary, our results demonstrate that XH at low micromolar concentrations might hold promise as a potent inhibitor of human pigmentation by primarily targeting melanin export and melanin degradation. Further studies to elucidate the signaling mechanisms of action of melanosome export inhibition by XH and in vivo efficacy are warranted.

Imperatorin Positively Regulates Melanogenesis through Signaling Pathways Involving PKA/CREB, ERK, AKT, and GSK3β/β-Catenin

“…The possible involvement of the above signaling pathways in stimulating melanin synthesis through imperatorin still needs to be investigated in the future. Although we have shown the melanogenic effects of imperatorin in B16F10 melanoma cells, the relative effectiveness of imperatorin in human normal melanocytes remains to be determined in future study [ 48 , 49 ]. In addition, the efficacy and safety of imperatorin-induced melanogenesis stimulation must be evaluated in vitiligo animal models and humans.…”

Antioxidant and pro-oxidant phytochemicals in ultrasound and microwave assisted extracts from hop cones: a statistical modelling approach

“…12 Interestingly, in human keratinocytes low concentrations of XH induce a significant stimulation of cell proliferation, whereas concentrations higher than 20 μM determine its reduction. 13 The biphasic effect of XH has been also reported in MCF7 cells, while 8-PN induces, in the same experimental condition, a slightly increase in cells viability. 14 XH, 6-PN, 8-PN and isoxanthohumol (IXH) exhibited an antiproliferative effect in different colorectal cancer cell lines, although different sensitivity of the cell lines and compound-related toxicity was evidenced.…”

Natural products in cosmetics

“…Xanthohumol at low concentrations is expected to be an effective inhibitor of human hyperpigmentation. It mainly targets melanin export in human melanocytes and melanin degradation in keratinocytes [ 94 ].…”