- 學位論文
楮樹莖部粗萃物及其化學成分之抗發炎活性與黑色素生成機轉探討
Mechanism of anti-melanogenesis and anti-inflammatory effects on the stem of Broussonetia kaempferi and its chemical constituents
摘要
皮膚照射到過量紫外線後可能會對於皮膚造成傷害，如:曬傷、皮膚乾燥、脫水、色素沉著、發炎、老化、皺紋甚至是癌症的產生，當活性氧分子 (reactive oxygen species, ROS)的受體直接或間接受到紫外線B的刺激後，將導致黑色素生成、發炎反應、以及細胞外基質降解。本研究將以人類角質細胞探討紫外線B照射能量與ROS誘發的關聯性、發炎相關因子測試與基質金屬蛋白酶含量試驗，並於小鼠黑色素腫瘤細胞進行黑色素生成相關蛋白機轉分析。楮樹 (Broussonetia kaempferi.)為一種桑科植物，經過萃取後獲得不同極性劃分層BKMS與BKEF，經活性導向，從BKEF分離出的十三個已知化合物並從中挑選出四個活性化合物kazinol M (1)、kazinol N (2)、(2S)-7,4'-dihydroxy-3'-methoxyflavan (3)及(±)-syringaresinol (4)進行本論文之探討。結果顯示kazinol M (1)與kazinol N (2)能抑制人類角質細胞內經紫外線照射所產生的ROS，並使其降至10.5 ± 6.2%與16.9 ± 4.2%，並主要透過大量激活p-ERK (phospho-extracellular regulated protein kinase)調節Trp-1 (tyrosinase related protein-1)與Trp-2 (tyrosinase related protein-2)的表現量而減少黑色素生成量。(2S)-7,4'-dihydroxy-3'-methoxyflavan (3)具有減少發炎因子IL-1β (interleukin-1β)的能力。(±)-syringaresinol (4)可以將TNF-α (tumor necrosis factor-α)的含量從440.9 ± 42.9%降低至271.9 ± 60.7%。此外化合物1-4皆能有效降低基質金屬蛋白酶-2與-9 (matrix metalloproteinases-2 and -9)的活性。本研究期望能由楮樹的成分中找到具有發展潛力的先導物，以利未來能開發成為化粧品用之活性添加劑。
並列摘要
Excess of solar ultraviolet (UV) irradiation may cause skin damages such as sunburn, dryness, dehydration, pigmentation, inflammation, aging, wrinkle, and even cancer. Direct UVB or indirect absorption by some receptors in the response to the generation of reactive oxygen species (ROS) leads to the origin of these damages, inflammatory reactions, extracellular matrix integrity degradation, and melanogenesis. The UVB-induced ROS production, the cytokines related to matrix metalloproteinase and inflammation in human keratinocytes (HaCaT), and the molecular aspects about melanogenesis mechanism performed in B16F10 melanoma cells are discussed in this study. Broussonetia kaempferi belong to Moraceae, two different soluble layers, namely BKMS and BKEF if this plant, were selected for the further evaluation. Bioassay-guided fractionation, thirteen known compounds were isolated from the stem of B. Kaempferi meanwhile, four active constituents, kazinol M (1), kazinol N (2), (2S)-7,4'-dihydroxy-3'-methoxyflavan (3), and (±)-syringaresinol (4) were selected to process biological assay. Kazinol M (1) and kazinol N (2) could not only inhibit intracellular ROS content to 10.5 ± 6.2% and 16.9 ± 4.2% but also decrease melanin formation, by down-regulating the level of Trp-1 (tyrosinase related protein-1) and Trp-2 (tyrosinase related protein-2), meanwhile, it also up-regulated the p-ERK (phospho-extracellular regulated protein kinase). Interleukin-1β (IL-1β) content was reduced by (2S)-7,4'-dihydroxy-3'-methoxyflavan (3). (±)-syringaresinol (4) decreased tumor necrosis factor-α (TNF-α) from 440.9 ± 42.9% to 271.9 ± 60.7%. Matrix metalloproteinases-2 and -9 (MMP-2 and -9) were all reduced effectively by compounds 1-4. Accordingly, the study of B. kaempferi is expected to find the lead precursor and it is looking forward to developing some active additive for the use of cosmetic industry.
參考文獻
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