楮樹化學成分及其作為黑色素抑制劑之研究

Chemical Constituents and Melanogenesis Inhibitors of Broussonetia kaempferi Sieb.

張芷綺(Chih-Chi Chang)

指導教授 ： 柯宏慧

高雄醫學大學/藥學院/香粧品學系碩士班/碩士(2014年)

摘要

皮膚過度暴露於紫外線的輻射下會造成色素沉著（如雀斑和斑點）的問題。近年來從天然植物中取得之黑色素抑制劑已為化粧品及醫藥工業的發展所重視。構樹屬植物已被報導具有很多活性，例如抗氧化、抗發炎、抗癌及美白等生物活性，然而對從楮樹萃取所得之化學成分及生物活性卻未能有深入之探討，為此，本研究乃針對楮樹莖部進行化學成分及生物活性的探討，並以生物活性為導向，由楮樹乙酸乙酯萃取層中分離到十三個化合物，分別為kazinol M (1)、 (2S)-7,4'-dihydroxy-3'- methoxyflavan (2)、(2S)-7,4′-dihydroxyflavan (3)、 isoliquiritigenin 2'- methylether (4)、(–)-liquiritigenin (5)、isoliquiritigenin (6)、(+)-marmesin (7)、kazinol N (8)、(?b)-syringaresinol (9)、quercetin (10)、kanzonol B (11)、(–)-butin (12)和lakoochin A (13)。將其進行美白活性篩選，結果顯示化合物1及8顯示具有顯著清除ABTS自由基之效果，其SC50值為13.4及19.1 μM。此外，化合物1具有很強的抑制蘑菇酪胺酸酶活性，其IC50值為1.2 μM，而在黑色素瘤細胞中觀察到化合物1雖具有降低黑色素含量的能力，但在酪胺酸酶活性上卻顯現出較弱的抑制作用。然而，化合物8之抑制蘑菇酪胺酸酶的效果雖比化合物1弱，但在細胞試驗中，8卻顯現出良好的酵素抑制活性及黑色素抑制效果，當在濃度10 μM時，黑色素之減少及酪胺酸酶的降低可分別達63%及32%。此外，化合物1與2混合後與純化合物1相比更可顯著地降低黑色素的含量，具加成作用。這些結果顯示由楮樹分離出的化合物具有成為黑色素抑制劑的潛能，然其詳細的作用機轉仍需繼續的研究與探討。

關鍵字

楮樹 ； 桑科 ； 成分 ； 黑色素抑制劑 ； 酪胺酸酶

並列摘要

Excessive exposure to ultraviolet (UV) radiation can cause abnormal pigmentation (freckles and spots) which may be an aesthetic problem; the use of melanogenesis inhibitor from natural plants to improve these skin disorders is becoming increasingly important in the cosmetic and medicinal industries. Broussonetia genus have been reported many bioactivities such as antioxidant, anti-inflammatiory, anticancer and anti-melanogenesis. However, the phytochemistry and biological activities of Broussonetia kaempferi have been studied rarely. Hence, this study focuses on the investigation of the bioactive constituents of B. kaempferi. Bioassay-guided isolation of the ethyl acetate soluble layer of B. kaempferi, including kazinol M (1), (2S)-7,4'-dihydroxy-3'- methoxyflavan (2), (2S)-7,4'-dihydroxyflavan (3), isoliquiritigenin 2'-methyl- ether (4), (–)-liquiritigenin (5), isoliquiritigenin (6), (+)-marmesin (7), kazinol N (8), (?b)-syringaresinol (9), quercetin (10), kanzonol B (11), (+)-butin (12) and lakoochin A (13). In results, compounds 1 and 8 exhibited significantly ABTS cation radical-scavenging effect with an SC50 values of 13.4 and 19.1 μM, respectively. Compound 1 showed strong inhibitory effect on mushroom tyrosinase with an IC50 value of 1.2 μM, interestingly, it showed melanin reduction but with a weak inhibitory effect on tyrosinase in B16F10 melanoma cells. Moreover, 8 with a slight inhibitory effect on tyrosinase, showing a stronger effect on reducing intracellular melanin content and tyrosinase activity than 1. It can reduce 63% intracellular melanin content and 32% tyrosinase activity at 10 μM. Besides, the combination of compounds 1 and 2 demonstrated a synergistic reduction of melanin biosynthesis, showing the significant difference from 1 alone. These results suggest that isolates of this plant may be candidate melanogenesis inhibitors. However, further investigations are required to determine their mechanisms of action.

並列關鍵字

Broussonetia kaempferi ； Moraceae ； Constituent ； Melanogenesis inhibitor ； Tyrosinase

參考文獻

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