8-11-dihydroxy-8-angeloyl-11-acetyl-4-guaien-3-one and Skin-Neoplasms

Epidermal melanocytes synthesize melanin pigments and transfer them to keratinocytes, which is responsible for skin pigmentation. However, abnormal accumulation of melanin pigments causes hyperpigmentation disorders, which are substantially improved with treatment of tyrosinase inhibitor. In our ongoing study, Torilis japonica DC. (Umbelliferae) was found to inhibit melanin production. A goal of this study is to elucidate the hypopigmenting principle of T. japonica. A sesquiterpene structure of torilin was isolated from the plant extracts via bioassay-guided phytochemical analysis. Torilin dose-dependently inhibited melanin production, with an IC(50) value of 25 microM, in alpha-melanocyte stimulating hormone (alpha-MSH)-activated B16 melanoma cells. Arbutin, a positive control of skin whitener, also inhibited alpha-MSH-induced melanin production with an IC(50) value of 170 microM. As to the mode of action, torilin downregulated alpha-MSH-induced protein levels of tyrosinase without directly inhibiting catalytic activity of the enzyme. Taken together, this study shows that torilin contributes to the hypopigmenting principle of T. japonica, and suggests its pharmacological potential in melanin-associated hyperpigmentation disorders.

Topics: alpha-MSH; Animals; Apiaceae; Arbutin; Dermatologic Agents; Dose-Response Relationship, Drug; Down-Regulation; Fruit; Hyperpigmentation; Inhibitory Concentration 50; Melanins; Melanoma, Experimental; Mice; Monophenol Monooxygenase; Phytotherapy; Plant Extracts; Sesquiterpenes, Guaiane; Skin; Skin Neoplasms; Skin Pigmentation