| 摘要: | 有許多研究指出生育三烯醇具有降低膽固醇、抗氧化及抗癌活性。但在抗黑色素合成的作用機制上，尚未有相關文獻。因此，本研究首次深入探討δ-生育三烯醇作用在皮膚美白、抗黑色素的分子作用機制。本研究的目的可分為三大方向: (1)評估生育三烯醇 (α、γ和δ三種異構物)及熊果素作用於B16黑色素瘤細胞後之細胞存活率，(2)研究δ-生育三烯醇與熊果素對B16細胞的活性氧自由基 (ROS)產生的影響，(3)檢測δ-生育三烯醇與熊果素對B16細胞的黑色素含量及黑色素生成的相關蛋白質表現，如酪胺酸酶、黑色素皮質素接受器1 (MC1R)、Mitf、酪胺酸酶相關蛋白質1 (TRP-1)及酪胺酸酶相關蛋白質2 (TRP-2)，與MAPK分子路徑的影響。由實驗結果發現δ-生育三烯醇是當中最能保護B16細胞的藥物。又有其他實驗的結果顯示20 μM的δ-生育三烯醇可顯著降低活性氧自由基 (ROS)的生成及抑制黑色素的產生，與降低酪胺酸酶、黑色素皮質素接受器1 (MC1R)、Mitf、酪胺酸酶相關蛋白質1 (TRP-1)及酪胺酸酶相關蛋白質2 (TRP-2)之mRNA表現。δ-生育三烯醇與細胞作用後，可顯著的提升調節活化及磷酸化的ERK，抑制磷酸化的p38表現，而降低黑色素的合成。這些結果顯示，δ-生育三烯醇具有抑制黑色素生成與抗氧化之雙向作用。
Several studies have shown that tocotrienols displayed the cholesterol lowering effect, antioxidative and anti-cancer activities. The study has not about antimelanogenesis mechanism (s) of δ-tocotrienol. So our study the effects of δT3 on skin-whitening agent and antimelanogenesis mechanism (s) in the first. In this study, our aims were (1) to evaluate the effect of α-, γ-, δ-tocotrienols (αT3, γT3, and δT3), and arbutin on cell viability, (2) to study the effects of δT3 and arbutin on the ROS production, and (3) to examine the effects of δT3 and arbutin on the melanin content, the expression of melanogenesis-related proteins such as tyrosinase, MC1R, Mitf, TRP (-1 and -2) and MAPK pathway in B16 melanoma cells. We found that δT3 possessed the best protective effect in B16 cells. Our data indicated that 20 μM δT3, but not arbutin, significantly decreased the generation of ROS, as a specific inhibitor of melanin production and reduced the expression of tyrosinase, MC1R, Mitf, TRP (-1 and -2) mRNA. Cells treated with δT3, and also markedly up-regulated the activation and phosphorylation of ERK kinases, down-regulated the phosphorylation of p38 kinase, and reduced melanin synthesis. These results suggest that δT3 performed well in both melanogenesis inhibition and antioxidation. |
