Sunlight exposure is inevitable to all humans and UV radiation in the sunlight usually causes damages to the skin. Tanning, first appearing when UV injures occur, is a pigmentation process which can be considered as a natural defense mechanism of the organism. Melanin plays an important role in the prevention of the skin from harmful environmental factors such as UV radiation. However, the excess accumulation of melanin causes hyperpigmentation, which is associated with a number of unhealthy conditions including solar lentigines, melasma, freckles and post-inflammatory hyperpigmentation. Therefore, the development of safe and effective hypopigmenting agents is of great importance.
The depigmenting effects of oxyresveratrol and trans-dihydromorin, as well as moracenin D, sanggenon T, mulberrofuran G and kuwanon O, were investigated in murine b16f10 melanoma cell line and its synergetic non-tumor melanocyte melan-a cells. All these six resorcinol type phenolic compounds (RTPs) were found to reveal significant hypopigmenting effects in murine b16f10 melanoma cell line. Oxyresveratrol and Kuwanon O presented the greatest inhibition on melanin synthesis at low concentration with the suppression on tyrosinase activity. However, in melan-a cells, only oxyresveratrol, trans-dihydromorin, kuwanon O and sanggenon T decreased melanin content significantly. The subsequent mechanisms studies explained the difference. In b16 cells, all of these RTPs induced post-transcriptional degradations of MITF without suppressing its mRNA expression, leading to significant decreases of TRP-1 and TRP-2 production, while in melan-a cells, the levels of tyrosinase, as well as TRP-1and TRP-2 were suppressed by MITF downregulation at both transcription and translation level. Among these RTPs, kuwanon O induced the greatest suppression on the tyrosinase families via MITF down-regulation. Sanggenon T, trans-dihydromorin and oxyresveratrol also exhibited same action of mechanism with weaker activities than kuwanon O. Further evaluations in artificial skin model demonstrated the outstanding depigmenting effects of kuwanon O, sanggenon T and trans-dihydromorin. The inhibitory effect by oxyresveratrol is negligible. It can be therefore inferred that a non-tumor melanocytes system might be more suitable for screening depigmenting agents applied to normal skin cells. Hypopigmenting agents effective in b16 melanoma system may not be so effective on normal melanocytes. Meanwhile, according to the structure-activity relationships studies of theses RTPs, to screen or synthesize resorcinol flavonone derivatives with an isoprenyl group in the Diels-Alder substituent might be a novel approach for the search of potent hypopigmenting agents.
The photoprotective effects of these RTPs were also investigated, as UV radiation not only dominants the skin tanning level, but also induces genetic damage and mutations in the epidermal basal layer of human skin. Oxyresveratrol and kuwanon O were found to reveal photoprotective effects on human primary epidermal keratinocytes by enhancement of DNA repair after 4.32 J/cm2 UVA radiation. They exhibited suppressions on cellular ROS induced by UVA and H2O2. Nitrotyrosine levels enhanced by UVA irradiation were also suppressed by them. Moreover, oxyresveratrol even increased cell viability after 4.32 J/cm2 UVA radiation. The possibility of oxyresveratrol and kuwanon O for prevention of photocarcinogenesis in humans is a potential avenue for investigation.
In summary, the research contributed to the knowledge of depigmenting and photoprotective effects of resorcinol type phenolic compounds from natural sources. The findings support natural polyphenols as cosmetic ingredients or pharmaceutical composition in purpose of skin lightening or clinic therapy. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy
| Identifer | oai:union.ndltd.org:HKU/oai:hub.hku.hk:10722/207207 |
| Date | January 2014 |
| Creators | Hu, Shuting, 胡舒婷 |
| Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
| Source Sets | Hong Kong University Theses |
| Language | English |
| Detected Language | English |
| Type | PG_Thesis |
| Rights | Creative Commons: Attribution 3.0 Hong Kong License, The author retains all proprietary rights, (such as patent rights) and the right to use in future works. |
| Relation | HKU Theses Online (HKUTO) |
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