A Novel Melanin Inhibitor: Hydroperoxy Traxastane-Type Triterpene from Flowers of Arnica montana

• Published in: Biological & pharmaceutical bulletin Vol. 30; no. 5; pp. 873 - 879
• Main Authors: Maeda, Kazuhisa, Naitou, Tomoko, Umishio, Kenichi, Fukuhara, Tadao, Motoyama, Akira
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.05.2007
• Subjects: Animals; Arnica - chemistry; Cell Line, Tumor; Culture Media; depigmentation; Dose-Response Relationship, Drug; Flowers - chemistry; hydroperoxy group; melanin; Melanins - antagonists & inhibitors; Melanins - biosynthesis; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Mice; Molecular Structure; Monophenol Monooxygenase - metabolism; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; traxastane; triterpene; Triterpenes - isolation & purification; Triterpenes - pharmacology; tyrosinase
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.30.873

We isolated a novel inhibitor of melanin biosynthesis from the flowers of Arnica montana L. (Compositae), and identified it as a traxastane-type triterpene (3β,16β-dihydroxy-21α-hydroperoxy-20(30)-taraxastene) [1] by means of 1D or 2D-NMR and liquid chromatography/high-resolution mass spectrometry (LC-HR-MS). Compound [1] at the concentration of 0.53 μM completely inhibited melanin accumulation in cultured B16 melanoma cells. It is one of the most potent among known plant inhibitors of melanin biosynthesis in cultured cells, being 50 times more potent than 4-methoxyphenol, which is used as an anti-pigmentation agent. Its mechanism of action is considered to involve inhibition of transcriptional factor MITF-M (melanocyte-type isoform of microphthalmia-associated transcription factor), which would lead to a decrease of tyrosinase and related genes. We confirmed that compound [1] decreased the protein levels of tyrosinase and its related proteins in B16 melanoma cells. Further study revealed that a similar hydroperoxy triterpene also suppressed the melanin pigment accumulation of B16 melanoma cells. These results indicate that the hydroperoxy group may play an important role in the suppression of the melanin accumulation by compound [1].