抗糖尿病植物新藥前端開發：綠色製程香椿萃取物

Pilot Investigation of A New Anti-diabetic Botanical Drug—Toona sinensis Extract Produced by Green-processed Technology

蔡逸宏(Yi-Hong Tsai)

指導教授 ： 張芳榮

共同指導教授 ： 吳永昌(Yang-Chang Wu)

高雄醫學大學/藥學院/天然藥物研究所博士班/博士(2016年)

摘要

全世界肥胖人口與日俱增，同時也帶來日益嚴重的健康問題，如代謝症候群等。尤其以糖尿病來說，輕忽血糖值不穩定及持續過高則很容易產生致命性併發症。臨床糖尿病用藥的全球市場需求也因此而蓬勃成長中。然而, 諸多藥品甚至某些明星藥品，卻因其於上市後臨床試驗監視期中陸續出現的嚴重副作用而逐漸沒落。
本研究利用超臨界流體萃取儀，生產超臨界香椿萃取物TS-SCF，發現於3T3-L1脂肪細胞抗代謝症候群篩選平台中可以改善細胞外葡萄糖利用率及抑制細胞內的油滴累積現象。經急性極限毒性試驗確認沒有立即的毒性。第二型糖尿病活體動物模式的測試則發現TS-SCF具延緩第二型糖尿病形成及改善胰島素抗性的功效，且能改善三酸甘油酯過高的現象、降低肝功能指數血清轉胺酶ALT及腎功能指數血清肌酸酐水平。病理組織切片的觀察則發現TS-SCF具有抑制腹部脂肪組織肥大且避免脂肪肝浸潤產生，推測可能與TS-SCF使血漿中adiponectin水平的升高有關。經氣相層析儀分析驗證，成分與主要由抗氧化成分組成的香椿水萃物迥異。TS-SCF的致效機制也已完成部分研究。對於開發改善第二型糖尿病及代謝症候群藥物的預防性替代補充食品或甚至植物新藥，TS-SCF深具潛力。

關鍵字

香椿 ； 超臨界流體萃取 ； 第二型糖尿病

並列摘要

The growing population of obesity brings the increasingly serious health problems, especially on metabolic syndrome and diabetes. To neglect the unstable and sustained high blood glucose level is very easy to lead the occurrence of some fatal complications. However, many drugs and even some star products were declined progressively due to the occurrences of serious side effects during the phase IV monitored trials.
In this study, we produced a supercritical fluid Toona sinensis extract, so called TS-SCF. We found that TS-SCF can improve extracellular glucose consumption and intracellular fat drop accumulation in 3T3-L1 adipocytes. There was no acute toxicity on TS-SCF confirmed through acute toxicity limit test. The type II diabetic animal model showed that TS-SCF got the ability to delay deterioration of type II diabetes and even could improve insulin resistance. Serum triglyceride, ALT and creatinine level were also very stable in the model after TS-SCF treatment. The observations of histopathological examination showed that TS-SCF can inhibit swelling of abdominal adipose tissue and occurrence of fatty liver accumulation. The effect was supposed to the result from the elevation of serum adiponectin level. The components of biological activities analyzed by GC/MS were different from the aqueous Toona sinensis extract composed of antioxidant constituents. The functional mechanisms of actions mentioned above were also investigated.
To research and develop a supplementary food or even a new botanical drug for improving type II diabetes and metabolic syndrome, TS-SCF is a potential candidate.

並列關鍵字

Toona sinensis ； supercritical fluid extract ； type II diabetes

參考文獻

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