葶花水竹葉化學成份及白鳳菜抗肝癌活性研究

Studies on the Chemical Constituents of Murdannia edulis and Anti-Liver Cancer Activities of Gynura divaricata

夏祖翔(Tsu-Hsiang Shia)

指導教授 ： 顏嘉宏

高雄醫學大學/藥學院/天然藥物研究所碩士班/碩士(2016年)

摘要

肝癌是全世界第六常見的癌症。然而，目前治療的效果仍然有限，因此，找尋具有新穎性療效之藥物是當務之急的。
在台灣民間中草藥中，葶花水竹葉[Murdannia edulis (Stokes) Faden]和白鳳菜[Gynura divaricata (L.) DC. ssp. formosana]被用來治療肝臟方面疾病。在 AlamarBlue® assay和細胞群落形成形成試驗(clonogenic assay)的結果顯示白鳳菜水萃取物展現藥效與劑量呈正相關性的Huh7細胞毒殺性(IC50: 555 µg/ml)與細胞群落形成(IC50: 390 µg/ml)。此外，白鳳菜水萃取物可以使Huh7細胞敏感於化學藥物Cisplatin, 5-Fluorouracil，增強化學治療的效果。有趣地是，我們發現白鳳菜水萃取物對於Huh7細胞的球體形成有更好的抑制效果。另外，白鳳菜水萃取物可以降低Huh7球體細胞之癌症幹細胞標誌(CD133, CD13, SOX2和OCT4)。Wnt訊息路徑在癌症幹細胞的續存扮演了重要的角色。我們發現在白鳳菜水萃取物治療下，可以降低Wnt訊息路徑的標記基因(c-MYC, CYCLIN D1, p27)。更重要地是，白鳳菜水萃取物展現藥效與劑量呈正相關性的抑制Huh7球體細胞之活化態β-catenin。根據我們的發現，說明了白鳳菜水萃取物可以藉由抑制Wnt pathway來針對癌症幹細胞，其潛藏之治療效果能成為肝細胞癌病患治療上的食物補充品。
葶花水竹葉(鴨跖草科)全株經由乙醇萃取，分離出三個新的香豆素和七個已知化合物，其化合物的抗發炎活性正在進行中。

關鍵字

白鳳菜 ； 葶花水竹葉 ； 肝癌

並列摘要

Liver canaer is the sixth common cancer in world wild. However, the treatment efficacy is limited. Thus, searching for novel therapeutic durg is urgently needed.
[Murdannia edulis (Stokes) Faden] (ME) and [Gynura divaricata (L.) DC .ssp. formosana] (GD) are commonly used to treat liver disorders in Taiwan folk medicine. Results from AlamarBlue® and clonogenic assay revealed that the water extract of GD induced a dose-dependent cytotoxicity and reduction of clony formation with IC50 values of 555 µg/ml and 390 µg/ml, respectively. Furthermore, GD extract sensitized Huh7 cells to chemotherapy such as cisplatin and 5-fluorouracil. Interestingly, we found that GD extract exerted a more profound inhibitory effect on sphere formation of Huh7 cells with IC50 values of 250 µg/ml. In addition, we showed that GD extract also caused reduction of cancer stem cell markers expression (CD133, CD13, SOX2, and OCT4). Wnt signaling pathway plays crucial role in cancer stem cell maintenance. We found that the expression of Wnt signaling target genes including c-MYC, CYCLIN D1 and p27 were reduced upon treatment of GD extract. More importantly, a dose-dependent suppression of active β-catenin was observed in GD extract treated Huh7 spheres. Accordingly, our findings suggested that G. divaricate could target cancer stem cell via suppressed Wnt pathway and be used as a food supplement for HCC patients with potential therapeutic benefits.
Three new coumarins (1 – 3), together with seven known ones (4 – 10), were isolated from the ethanolic extract of the whole plant of Murdannia edulis (Commelinaceae), the anti-inflammatory activities of isolated compounds are currently under investigation.

並列關鍵字

Gynura divaricata ； Murdannia edulis ； Liver Cancer

參考文獻

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