Anti-melanogenic Activity of Gagunin D by Modulation of Tyrosinase Expression and Degradation
티로시나아제의 발현과 분해 조절을 통한 Gagunin D의 미백 효능 기전 연구
- 약학대학 약학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 약학대학 약학과(천연물과학전공), 2017. 2. 이상국.
- Tyrosinase is the rate-limiting enzyme critical for melanin biosynthesis and controls pigmentation in the skin. Inhibition of tyrosinase has so far been the most common approach in the development of skin-whitening cosmetics. A number of tyrosinase inhibitors are used as cosmetic formulations. However, in this present study, a balance between tyrosinase expression and degradation is considered as a new target for skin whitening agent.
Gagunin D (GD), a highly oxygenated diterpenoid isolated from the marine sponge Phorbas sp., has exhibited cytotoxicity toward human leukemia cells (K562). However, the effect of GD on normal cells and the molecular mechanisms of action remain to be elucidated. In this study, The anti-melanogenic activity of GD and its precise underlying mechanisms in mouse originated melan-a cells were identified. GD significantly inhibited melanin synthesis in the melan-a cells without cytotoxicity and had an effect on a reconstructed human skin model composed of human epidermis and melanocytes.
Further analysis revealed that GD suppressed the expression of tyrosinase and increased the rate of tyrosinase degradation. GD also inhibited tyrosinase enzymatic activity. In addition, GD effectively suppressed the expression of proteins associated with melanosome-transfer.
These findings suggest that GD is a potential candidate for cosmetic formulations due to its multi-functional properties which replaces tyrosinase inhibitor.