Daffix1, C., Lemesle1, A, Robert1, C., Rabhi2, C.; Pouligon2, M., Jean2, D., Schwaab1, V. 1Department of Biology, LMD Pharmacognosie, Veyre-Monton, France. 2Department of Chemistry, LMD Pharmacognosie, Veyre-Monton, France.

Tyrosinase has long been commonly considered as the sole enzyme involved in melanogenesis and has served as target to develop whitening agents. But, over the past decade, it has become well accepted that melanins pathways involve many other enzymes such as Nitric Oxide Synthase (NOS) and/or peroxidase-H2O2 as well as many integrative phenomena such as the cross-talk between keratinocytes and melanocytes including the paracrine factor Nitric Oxide Radical. The aim of this study was to search for natural active molecules with a complete depigmenting approach. LMD Pharmacognosie investigations supported by ethnobotanical data showed that a product extracted from a Brassicaceae plant was able to prevent vegetable browning. Phytochemical screening and chemical synthesis were performed to determine the active molecules. Their potential inhibition of the melanins synthesis enzymatic pathways and their depigmenting effect on melanoma cell culture and skin equivalent tissue model were studied. One molecule from the plant extract was highlighted for its significant ability to inhibit pigmentation. The results show that this molecule is an inhibitor of NOS, peroxidase and tyrosinase. Regarding its action on cell culture, the inhibitory effect can reach 6% versus 4% for the ascorbic acid control and, on skin equivalent, 30% with no cytotoxic effects compared with kojic acid and ascorbic acid that both show a significant cytotoxic effect. Moreover, we showed that this molecule protects keratinocytes against UV-mutagenic effects. All data argue that depigmenting effects are explained in part by inhibition of the major enzymes involved in melanogenesis and especially, inhibition of the NO synthesis with respect to its central role in the regulation of the melanogenesis. This new molecule represents a safe and efficient alternative to reduce skin pigmentation.


Cathecol, DOPA, Dopaquinone, Free radical detoxification, Hydroquinone, Keratinocytes, L-DOPA, LM-F3, Melanin pigments, Melanin synthesis, MelanoDerm, Melanocytes, Melanogenesis, Nitric oxide, Nitric oxide peroxidase-H202, Nitric oxide radical, Nitric oxide synthase (NOS), Peroxidase, Photobiology, Pigmentation, ROS, Superoxide dismutase, Tyrosinase, Tyrosinase inhibitor, UV-mutagenic effects

Materials Tested

LM-F3, Skin whitening agents

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