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DOI: 10.1055/s-0035-1565317
Ursolic acid and 12-O-methylcarnosic acid from the leaves of Rosmarinus officinalis L. suppressed melanin production with downregulation of tyrosinase expression in HMV-II melanoma cells
Horticultural therapy involves horticultural activity for elderly or disabled individuals, with the aim of improving quality of life (QOL). Experimental data showing improved QOL from horticultural plants would indicate objective benefits from horticultural therapy. We evaluated the skin-whitening effects of horticultural therapy plants on melanogenesis in HMV-II human melanoma cells.
A total of 15 samples of extracts obtained from horticultural herbal therapy plants were examined. Based on IC50 values, the highest inhibitory effect on melanogenesis was observed with extracts from the leaves of Rosmarinus officinalis L. (rosemary). This extract showed stronger activity than the flowers of Erica vulgaris (heath), which include abundant levels of the major skin whitening compound, arbutin (positive control). Next, we isolated active compounds from rosemary by melanogenesis inhibitory activity-guided fractionation, identifying ursolic acid (1) and 12-O-methylcarnosic acid (2) as the main bioactive compounds. Compared with 1 and its isomers (betulinic acid (3) and oleanic acid (4)) at the concentration of 7.5 µM, inhibitory effects of 1 and 3 were 67.2 ± 9.4% and 0.5 ± 0.5% (% to control), respectively. Compound 3 showed high cytotoxicity (viability, 7.4 ± 1.4%), while 4 had no effect inhibiting melanogenesis. Tyrosinase is one of the key enzymes involved in melanogenesis. We therefore studied whether these compounds would suppress expression of tyrosinase on HMV-II cells. Compounds 1, 2, and 3 showed downregulation of tyrosinase expression, according to the results of western blotting.
![](https://www.thieme-connect.de/media/plantamedica/201516/10-1055-s-0035-1565317-isl3b_04.jpg)
The anti-melanogenesis activity of 1 on B16 mouse melanoma cell has been reported. However, these findings offer the first report of the anti-melanogenetic activity of 1 and 2 on HMV-II human melanoma cells and their mechanism. Anti-melanogenetic compounds isolated from rosemary are currently under investigation.