臺灣博碩士論文加值系統

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。

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.

目 錄
目錄----------------------------------------------------------------------------------I
圖目錄----------------------------------------------------------------------------IV表目錄---------------------------------------------------------------------------VI
第一章 緒論-----------------------------------------------------------------------1
第一節 前言----------------------------------------------------------------1
第二節 代謝症候群及糖尿病-------------------------------------------5
第三節 臨床常用抗糖尿病藥------------------------------------------22
第四節 臨床抗糖尿病藥之市場分析及預測------------------------32
第五節 研究動機---------------------------------------------------------34
第六節 香椿的簡介及文獻回顧---------------------------------------35
第七節 專利檢索與科學文獻之交叉分析與探索------------------41
第八節 溶媒與超臨界流體萃取---------------------------------------45
第九節 研究目的與架構設計------------------------------------------48
第二章 研究材料與方法------------------------------------------------------51
第一節 植物材料、試劑與儀器----------------------------------------51
第二節 香椿中、高極性萃取物----------------------------------------53
第三節 3T3-L1脂肪細胞抗代謝症候群篩選平台----------------- 54


第四節 超臨界香椿萃取物TS-SCF口服單一劑量急性
極限毒性試驗---------------------------------------------------58
第五節 第二型糖尿病活體動物模式---------------------------------60
第六節 口服葡萄糖耐受性試驗---------------------------------------64
第七節 香椿葉萃取物之性質區別------------------------------------65
第八節 氣相層析串聯質譜分析超臨界香椿萃取物---------------66
第九節 統計分析---------------------------------------------------------68
第三章 實驗結果與討論------------------------------------------------------69
第一節 超臨界⾹椿萃取物TS-SCF促進3T3-L1脂肪細
胞對胞外葡萄糖的利用率與抑制油滴累積形成
的作用------------------------------------------------------------69
第二節 口服單一劑量超臨界香椿萃取物TS-SCF急性
極限毒性試驗---------------------------------------------------76
第三節 超臨界香椿萃取物TS-SCF 改善或延緩第二型
糖尿病⿏惡化的現象------------------------------------------79
第四節 超臨界香椿萃取物TS-SCF對第二型糖尿病鼠
各種生化檢驗值之影響---------------------------------------85
第五節 超臨界⾹椿萃取物TS-SCF對第二型糖尿病鼠
改善⼝服葡萄糖耐受性的能力------------------------------89
第六節 超臨界香椿萃取物TS-SCF改善第二型糖尿病
⿏肝臟組織浸潤及腹部脂肪組織肥大的現象------------91
第七節 超臨界⾹椿萃取物TS-SCF對第二型糖尿病鼠
之血清中Adiponectin和TNF-α的影響---------------------94
第八節 超臨界香椿萃取物TS-SCF功效性試驗總結及
其成分化合物鑑定與層析指紋圖譜建立------------------97
第九節 超臨界香椿萃取物TS-SCF與親水性中、高極
性香椿萃取物之活性及成分區別-------------------------103
第十節 超臨界香椿萃取物TS-SCF抗第二型糖尿病及
代謝症候群活性之作用機制-----------------------------111
第四章 結論與目前進展及未來規劃--------------------------------------112
第一節 實驗結果結論-------------------------------------------------112
第二節 目前進展及未來規劃----------------------------------------118
第五章 參考文獻--------------------------------------------------------------121
第六章 研究成果列表--------------------------------------------------------146
第七章 附錄（文章發表）-----------------------------------------------------148圖目錄
圖一、代謝症候群-----------------------------------------------------------------5
圖二、胰島素及其阻抗性與身體組織及器官的關係---------------------14
圖三、TNF-α及adiponectin在代謝症候群中的角色----------------------19
圖四、糖尿病患者可能遭受的全身性症狀及致命併發症---------------20圖五、香椿（Toona sinensis, TS）-------------------------------------------- 35圖六、香椿水萃取物的主要成分gallic acid--------------------------------39
圖七、香椿之技術×功效矩陣圖----------------------------------------------42
圖八、香椿之技術×功效×成分極性3D分析圖----------------------------43
圖九、超臨界二氧化碳（sc-CO2）---------------------------------------------46
圖十、NATEX Process Technology GmbH 5 liters /1000 bar
R&D unit超臨界萃取儀-----------------------------------------------47
圖十一、研究架構設計圖------------------------------------------------------50
圖十二、香椿中、高極性萃取裝置圖-----------------------------------------53
圖十三、3T3-L1脂肪細胞抗代謝症候群篩選平台：葡萄糖
利用率及脂肪油滴累積評估-----------------------------------------55
圖十四、第二型糖尿病活體動物模式---------------------------------------63
圖十五、Thermo DSQ II Single Quadrupole GC/MS-----------------------67

圖十六、TS-SCF於3T3-L1脂肪細胞中對胞外葡萄糖利用率之評估--74
圖十七、TS-SCF於3T3-L1脂肪細胞中抑制油滴累積形成作用的評--75
圖十八、第二型糖尿病鼠八週實驗體重變化圖---------------------------83
圖十九、第二型糖尿病鼠八週實驗血糖變化圖---------------------------84圖二十、超臨界香椿萃取物TS-SCF對第二型糖尿病鼠口服
葡萄糖耐受性試驗結果圖--------------------------------------------90
圖二十一、第二型糖尿病的成分分析與﷽﷽﷽﷽﷽﷽﷽﷽上則尚未達到明顯差異﷽﷽﷽﷽﷽﷽﷽﷽﷽﷽﷽﷽﷽活體動物脂肪及肝臟組織病理切片圖------93
圖二十二、投予超臨界香椿萃取物TS-SCF的第二型糖尿病
鼠之血清adiponectin和TNF-α圖------------------------------------96
圖二十三、超臨界香椿萃取物TS-SCF的氣相層析串聯質譜
儀層析指紋圖譜------------------------------------------------------101
圖二十四、TS-SCF與親水性中、高極性香椿萃取物於3T3- L1
脂肪細胞對胞外葡萄糖利用率的評估結果---------------------106
圖二十五、TS-SCF與親水性中、高極性香椿萃取物的物理
性質差異---------------------------------------------------------------109
圖二十六、超臨界香椿萃取物TS-SCF整體研究結果結論圖----------117
圖二十七、香椿葉超臨界萃取物TS-SCF的原型錠劑產品試製-------119表目錄
表一、過去常用之代謝症候群臨床判別準則--------------------------------6
表二、不同族群間腰圍之肥胖臨界值判別基準-----------------------------8
表三、糖尿病的流行率---------------------------------------------------------12
表四、最新的糖尿病的診斷基準---------------------------------------------12
表五、臨床常用抗糖尿病藥物之主要類別---------------------------------29
表六、2014年全球糖尿病藥品市場之前5大廠商--------------------------32
表七、TS-SCF急性極限毒性試驗之動物症狀觀察與死亡率------------78
表八、超臨界香椿萃取物TS-SCF對第二型糖尿病鼠各種生
化檢驗值影響-----------------------------------------------------------88
表九、超臨界香椿萃取物TS-SCF的化學成分組成表-------------------102

Abdul-Ghani, M.A., DeFronzo, R.A., 2008. Inhibition of renal glucose reabsorption： A novel strategy for achieving glucose control in type 2 diabetes mellitus. Endocrine Practice 14, 782-790.
Adams, R.P., 2001. Identification of essential oil components by gas chromatography-quadrupole mass spectroscopy. Allured Publishing Corporation, Carol Stream, IL, USA.
Alberti, K.G. and Zimmet, P.Z., 1998. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabetic Medicine 15 (7), 539-553.
Alberti, K.G., Eckel, R.H., Grundy, S.M., Zimmet P.Z., Cleeman, J.I., Donato, K.A., Fruchart, J.C., James, W.P., Loria, C.M., Smith, S.C. Jr., 2009. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; National heart, lung, and blood institute; American heart association; World heart federation; International atherosclerosis society; and international association for the study of obesity. Circulation 120 (16), 1640-1645.
American Diabetes Association., 2013. Economic costs of diabetes in the U.S. in 2012. Diabetes Care 36, 1033-1046.
American Diabetes Association., 2014. Executive summary： Standards of medical care in diabetes--2014. Diabetes Care 37, S5-13.
American Diabetes Association., 2014. Standards of medical care in diabetes-2014. Diabetes Care 37, S14-80.
Arita, Y., Kihara, S., Ouchi, N., Takahashi, M., Maeda, K., Miyagawa, J., Hotta, K., Shimomura, I., Nakamura, T., Miyaoka, K., Kuriyama, H., Nishida, M., Yamashita, S., Okubo, K., Matsubara, K., Muraguchi, M., Ohmoto, Y., Funahashi, T., Matsuzawa, Y., 1999. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochemical and Biophysical Research Communications 257, 79-83.
Armato, J., Reaven, G.M., Ruby, R., 2015. Triglyceride/high-density lipoprotein cholesterol concentration ratio identifies accentuated cardio-metabolic risk. Endocrine Practice 9, 1-18.
Avandia to Carry Stronger Heart Failure Warning, 2007. Forbes.com. http://web.archive.org/web/20071021074525/http://forbes.com/forbeslife/health/feeds/hscout/2007/08/14/hscout607350.html.
Balkau, B. and Charles, M. A., 1999. Comment on the provisional report from the WHO consultation: European Group for the Study of Insulin Resistance (EGIR). Diabetic Medicine 16 (5), 442–443.
Bansal, N., 2015. Prediabetes diagnosis and treatment： A review. World Journal of Diabetes 6, 296-303.
Bays, H., 2009. From victim to ally： the kidney as an emerging target for the treatment of diabetes mellitus. Current Medical Research and Opinion 25, 671-681.
Bays, H., Mandarino, L., DeFronzo, R.A., 2004. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus： peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. Journal of Clinical Endocrinology and Metabolism 89, 463-478.
Chang, H.C., Hung, W.C., Huang, M.S., Hsu, H.K., 2002. Extract from the leaves of Toona sinensis Roem exerts potent antiproliferative effect on human lung cancer cells. American Journal of Chinese Medicine 30, 307-314.
Chang, H.L., Hsu, H.K., Su, J.H., Wang P.H., Chung, Y.F., Chia, Y.C., Tsai, L.Y., Wu, Y.C., Yuan, S.S., 2006. The fractionated Toona sinensis leaf extract induces apoptosis of human ovarian cancer cells and inhibits tumor growth in a murine xenograft model. Gynecologic Oncology 102, 309-314.
Charbonnel, B., Dormandy, J., Erdmann, E., Massi-Benedetti, M., Skene, A., 2004. The prospective pioglitazone clinical trial in macrovascular events (PROactive)： Can pioglitazone reduce cardiovascular events in diabetes? Study design and baseline characteristics of 5,238 patients. Diabetes Care 27, 1647-1653.
Chen, C.J., Michaelis, M., Hsu, H.K., Tsai, C.C., Yang, K.D., Wu, Y.C., Cinatl Jr., J., Doerrc, H.M., 2008. Toona sinensis Roem tender leaf extract inhibits SARS coronavirus replication. Journal of Ethnopharmacology 120, 108-111.
Chen, H.M., Wu, Y.C., Chia, Y.C., Chang, F.R., Hsu, H.K., Hsieh, Y.C., Chen, C.C., Yuan, S.S., 2009. Gallic acid, a major component of Toona sinensis leaf extracts, contains a ROS-mediated anticancer activity in human prostate cancer cells. Cancer Letters 286, 161-171.
Chen, H.Y., Tsai, W.C., Chiu, Y.L., Hsu, S.P., Pai, M.F., Yang, J.Y., Peng, Y.S., 2015. Triglyceride to high-density lipoprotein cholesterol ratio predicts cardiovascular outcomes in prevalent dialysis patients. Medicine 94 (10), e619, 7 pages.
Cheng, A.Y., Fantus, I.G., 2005. Oral antihyperglycemic therapy for type 2 diabetes mellitus. Canadian Medical Association Journal 172, 213-226.
Chiang, J.K., Lai, N.S., Chang, J.K., Koo, M., 2011. Predicting insulin resistance using the triglyceride-to-high-density lipoprotein cholesterol ratio in Taiwanese adults. Cardiovascular Diabetology 10 (93), 6 pages.
Cho, E.J., Yokozawa, T., Rhyu, D.Y., Kim, H.Y., Shibahara, N., Park, J.C., 2003. The inhibitory effects of 12 medicinal plants and their component compounds on lipid peroxidation. American Journal of Chinese Medicine 31, 907-917.
Cho, E.J., Yokozawa, T., Rhyu, D.Y., Kim, S.C., Shibahara, N., Park, J.C., 2003. Study on the inhibitory effects of Korean medicinal plants and their main compounds on the 1,1-diphenyl-2-picrylhydrazyl radical. Phytomedicine 10, 544-551.
Christensen, S.D., Mikkelsen, L.F., Fels, J.J., Bodvarsdottir, T.B., Hansen, A.K., 2009. Quality of plasma sampled by different methods for multiple blood sampling in mice. Laboratory Animals 43, 65–71.
Cleeman, J.I., 2001. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). Journal of the American Medical Association 285 (19), 2486–2497.
DeFronzo, R.A., 2004. Dysfunctional fat cells, lipotoxicity and type 2 diabetes. International Journal of Clinical Practice. Supplement 9-21.
DeFronzo, R.A., Abdul-Ghani, M., 2011. Type 2 diabetes can be prevented with early pharmacological intervention. Diabetes Care 34, 202-209.
Edmonds, J.M., Staniforth, M., 1998. Toona sinensis (Meliaceae). Curtis''s Botanical Magazine 15, 186-193.
Einhorn, D., Reaven, G.M., Cobin, R.H., Ford, E., Ganda, O.P., Handelsman, Y., Hellman, R., Jellinger, P.S., Kendall, D., Krauss, R.M., Neufeld, N.D., Petak, S.M., Rodbard, H.W., Seibel, J.A., Smith, D.A., Wilson, P.W., 2003. American College of Endocrinology position statement on the insulin resistance syndrome. Endocrine Practice 9 (3), 237-252.
Fan, S., Chen, H.N., Wang, C.J., Tseng, W.C., Hsu, H.K., Weng, C.F., 2007. Toona sinensis Roem (Meliaceae) leaf extract alleviates liver fibrosis via reducing TGFb1 and collagen. Food and Chemical Toxicology 45, 2228-2236.
Feng, H., Ma, H., Lin, H.Y., Putheti, R., 2009. Antifatigue activity of water extracts of Toona sinensis Roemor leaf and exercise-related changes in lipid peroxidation in endurance exercise. Journal of Medicinal Plants Research 11, 949-954.
Ford, E.S., Giles, W.H., Dietz, W.H., 2002. Prevalence of the metabolic syndrome among US adults： findings from the Third National Health and Nutrition Examination Survey. Journal of the American Medical Association 287, 356-359.
Fruebis, J., Tsao, T.S., Javorschi, S., Ebbets-Reed, D., Erickson, M.R., Yen, F.T., Bihain, B.E., Lodish, H.F., 2001. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proceedings of the National Academy of Sciences 98, 2005-2010.
Gerich, J.E., 2010. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus： therapeutic implications; Diabetic Medicine 27, 136-142.
Gloerich, J., Ven Der Brink, D.M., Ruiter, J.P.N., Ven Vlies, N., Vaz, F.M., Wanders, R.J.A., Ferdinandusse, S., 2007. Metabolism of phytol to phytanic acid in the mouse, and the role of PPAR in its regulation. Journal of Lipid Research 48, 77–85.
Grant, R.W., Kirkman, M.S., 2015. Trends in the evidence level for the American Diabetes Association''s "Standards of medical care in diabetes" from 2005 to 2014. Diabetes Care 38, 6-8.
Heim, M., Johnson, J., Boess, F., Bendik, I., Weber, P., Hunziker, W., Flühmann, B., 2002. Phytanic acid, a natural peroxisome proliferator-activated receptor agonist, regulates glucose metabolism in rat primary hepatocytes. Journal of Federation of American Societies for Experimental Biology 7, 718–720.
Hotta, K., Funahashi, T., Arita, Y., Takahashi, M., Matsuda, M., Okamoto, Y., Iwahashi, H., Kuriyama, H., Ouchi, N., Maeda, K., Nishida, M., Kihara, S., Sakai, N., Nakajima, T., Hasegawa, K., Muraguchi, M., Ohmoto, Y., Nakamura, T., Yamashita, S., Hanafusa, T., Matsuzawa, Y., 2000. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arteriosclerosis, thrombosis, and vascular biology 20, 1595-1599.
Hseu, Y.C., Chang, W.H., Chen, C.S., Liao, J.W., Huang, C.J., Lu, F.J., Chia, Y.C., Hsu, H.K., Wu, J.J., Yang, H.L., 2008. Antioxidant activities of Toona sinensis leaves extracts using different antioxidant models. Food and Chemical Toxicology 46, 105-114.
Hsieh, C.L., Lin, Y.C., Ko, W.S., Peng, C.H., Huang, C.N., Peng, R.Y., 2005. Inhibitory effect of some selected nutraceutic herbs on LDL glycation induced by glucose and glyoxal. Journal of Ethnopharmacology 102, 357-363.
Hsieh, T.J., Liu, T.Z., Chia, Y.C., Chern, C.L., Lu, F.J., Chuang, M.C., Mau, S.Y., Chen, S.H., Syu, Y.H., Chen, C.H., 2004. Protective effect of methyl gallate from Toona sinensis (Meliaceae) against hydrogen peroxide-induced oxidative stress and DNA damage in MDCK cells. Food and Chemical Toxicology 42, 843-850.
Hsu, H.K., Yang, Y.C., Hwang, J.H., Hong, S.J., 2003. Effect of Toona sinensis leaf extract on lipolysis in differentiated 3T3-L1 adipocytes. Kaohsiung Journal of Medical Sciences 19, 385-390.
Hu, E.A., Pan, A., Malik,V., Sun, Q., 2012. White rice consumption and risk of type 2 diabetes： meta-analysis and systematic review. British Medical Journal 344, 1454.
Huang, K.C., Chen, C.L., Chuang, L.M., Ho, S.R., Tai, T.Y., Yang, W.S., 2003. Plasma adiponectin levels and blood pressures in nondiabetic adolescent females. Journal of Clinical Endocrinology & Metabolism 88, 4130-4134.
Hung, W.W., Hsieh, T.J., Lin, T., Chou, P.C., Hsiao, P.J., Lin, K.D., Shin, S.J., 2011. Blockade of the renin-angiotensin system ameliorates apelin production in 3T3-L1 adipocytes. Cardiovascular Drugs and Therapy 25, 3-12.
Idris, I., Donnelly, R., 2009. Sodium-glucose co-transporter-2 inhibitors： an emerging new class of oral antidiabetic drug. Diabetes, Obesity and Metabolism 11, 79-88.
International Diabetes Federation., 2013. IDF DIABETES ATLAS Sixth edition. International Diabetes Federation, Belgium.
Israili, Z.H., 2011. Advances in the treatment of type 2 diabetes mellitus. American Journal of Therapeutics 18, 117-152.
Jiang, C., Ren, Q., Wu, P., 2003. Study on retention factor and resolution of tocopherols by supercritical fluid chromatography. Journal of Chromatography A 1005, 155-164.
Kang, Y.S. and Yoo, E.G., 2015. The triglyceride‐to‐high density lipoprotein cholesterol ratio in overweight Korean children. European Society for Paediatric Endocrinology 84, P‐3‐849.
Kashyap, S., Belfort, R., Gastaldelli, A., Pratipanawatr, T., Berria, R., Pratipanawatr, W., Bajaj, M., Mandarino, L., DeFronzo, R., Cusi, K., 2003. A sustained increase in plasma free fatty acids impairs insulin secretion in nondiabetic subjects genetically predisposed to develop type 2 diabetes. Diabetes 52, 2461-2474.
Kaur, J., 2014. A comprehensive review on metabolic syndrome. Cardiology Research and Practice 2014, article ID 943162, 21 pages.
Kinkel, A.D., Fernyhough, M.E., Helterline, D.L., Vierck, J.L., Oberg, K.S., Vance, T.J., Hausman, G.J., Hill, R.A., Dodson, M.V., 2004. Oil red-O stains non-adipogenic cells： a precautionary note. Cytotechnology 46, 49-56.
König, B., Koch, A., Spielmann, J., Hilgenfeld, C., Hirche, F., Stangl, G.I., Eder, K., 2009. Activation of PPARα and PPARγ reduces triacylglycerol synthesis in rat hepatoma cells by reduction of nuclear SREBP-1. Eur. European Journal of Pharmacology 605, 23–30.
Krisanapun, C., Lee, S.H., Peungvicha, P., Temsiririrkkul, R., Baek, S.J., 2011. Antidiabetic activities of Abutilon indicum (L.) sweet are mediated by enhancement of adipocyte differentiation and activation of the GLUT1 promoter. Evidence-Based Complementary and Alternative Medicine 2011, 1-9.
Lavigne, J.G., Belanger, P.M., Dore, F., Labrecque, G., 1983. Temporal variations in chloroform-induced hepatotoxicity in rats. Toxicology 26, 267-273.
Lian, J.H., Xiang, Y.Q., Guo, L., Hu, W.R., Ji, W., Gong, B.Q., 2007. The use of high-fat/carbohydrate diet-fed and streptozotocin-treated mice as a suitable animalmodel of type 2 diabetes mellitus. Scandinavian Journal of Laboratory Animal Science 34, 21-29.
Liao, J.W., Chung, Y.C., Yeh, J.Y., Lin, Y.C., Lin, Y.G., Wu, S.M., Chan, Y.C., 2007. Safety evaluation of water extracts of Toona sinensis Roemor leaf. Food and Chemical Toxicology 45, 1393-1399.
Liao, J.W., Hsu, C.K., Wang, M.F., Hsu, W.H., Chan, Y.C., 2006. Beneficial effect of Toona sinensis Roemor on improving cognitive performance and brain degeneration in senescence-accelerated mice. British Journal of Nutrition 96, 400-407.
Liao, J.W., Yeh, Y.C., Lin, Y.C., Wei, M.M., Chung, Y.C., 2009. Mutagenicity and safety evaluation of water extract of fermented Toona sinensis Roemor leaves. Journal of Food Science 74, 7-13.
List, J.F., Woo, V., Morales, E., Tang, W., Fiedorek, F.T., 2009. Sodium-glucose cotransport inhibition with dapagliflozin in Type 2 Diabetes. Diabetes Care 32, 650-657.
Luque de Castro, M.D., Garcia-Ayuso, L.E., 1998. Soxhlet extraction of solid materials： An outdated technique with a promising innovative future. Analytica Chimica Acta 369, 1-10.
Maher, G.R., 1967. Air pollution regulation of nonvehicular, organic-solvent emissions by Los Angeles Rule 66. Journal of the American Oil Chemists'' Society 44, 340-342.
Mannucci, E., Monami, M., Lamanna, C., Gensini, G.F., Marchionni, N., 2008. Pioglitazone and cardiovascular risk. A comprehensive meta-analysis of randomized clinical trials. Diabetes, Obesity and Metabolism 10, 1221-1238.
Matsuda, M., Shimomura, I., Sata, M., Arita, Y., Nishida, M., Maeda, N., Kumada, M., Okamoto, Y., Nagaretani, H., Nishizawa, H., Kishida, K., Komuro, R., Ouchi, N., Kihara, S., Nagai, R., Funahashi, T., Matsuzawa, Y., 2002. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. Journal of Biological Chemistry 277, 37487-37491.
Matsuzawa, Y., 2005. White adipose tissue and cardiovascular disease. Best Practice & Research Clinical Endocrinology & Metabolism 19, 637-647.
Matsuzawa, Y., Funahashi, T., Kihara, S., Shimomura, I., 2003. Adiponectin and metabolic syndrome. Arteriosclerosis, Thrombosis, and Vascular Biology 9, 9.
Michielin, E.M.Z., Salvador, A.A., Riehl, C.A.S., Smania Jr., A., Ferreira S.R.S., 2009. Chemical composition and antibacterial activity of Cordiaverbenacea extracts obtained by different methods obtained by different methods. Bioresource Technology 100, 6615-6623.
Molinari, G., 2009. Natural products in drug discovery: present status and perspectives. Advances in Experimental Medicine and Biology 655, 13-27.
Murakami N, Ohtsubo, T., Kansui, Y., Goto, K., Noguchi, H., Haga, Y., Nakabeppu, Y., Matsumura, K., Kitazono, T., 2013. Mice heterozygous for the xanthine oxidoreductase gene facilitate lipid accumulation in adipocytes. Arteriosclerosis, Thrombosis, and Vascular Biology 34, 44-51.
Murguía-Romero, M., Jiménez-Flores, J.R., Sigrist-Flores, S.C., Espinoza-Camacho, M.A., Jiménez-Morales, M., Piña, E., Méndez-Cruz, A.R., Villalobos-Molina, R., Reaven, G.M., 2013. Plasma triglyceride/high-density lipoprotein cholesterol ratio, insulin resistance, and cardio-metabolic risk in young men and women. Journal of Lipid Research 54 (10), 2795-2799.
Newman, D.J. and Cragg, G.M., 2007. Natural products as sources of new drugs over thelast 25 years. Journal of Natural products 70 (3), 461-477.
Newman, D.J. and Cragg, G.M., 2012. Natural products as sources of new drugs over the 30 years from 1981 to 2010. Journal of Natural products 75 (3), 311–335.
Nissen, S.E., Nicholls, S.J., Wolski, K., Nesto, R., Kupfer, S., Perez, A., Jure, H., De Larochellière, R., Staniloae, C.S., Mavromatis, K., Saw, J., Hu, B., Lincoff, A.M., Tuzcu, E.M., 2008. Comparison of Pioglitazone vs Glimepiride on progression of coronary atherosclerosis in patients with Type 2 diabetes. Journal of the American Medical Association 299, 1561-1573.
Ogurtsova, K., 2014. Studies used to generate the 2014 IDF diabetes atlas estimates of diabetes prevalence in adults (20-79). International Diabetes Federation.
Okamoto, Y., Kihara, S., Ouchi, N., Nishida, M., Arita, Y., Kumada, M., Ohashi, K., Sakai, N., Shimomura, I., Kobayashi, H., Terasaka, N., Inaba, T., Funahashi, T., Matsuzawa, Y., 2002. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 106, 2767-2770.
Ouchi, N., Kihara, S., Arita, Y., Maeda, K., Kuriyama, H., Okamoto, Y., Hotta, K., Nishida, M., Takahashi, M., Nakamura, T., Yamashita, S., Funahashi, T., Matsuzawa, Y., 1999. Novel modulator for endothelial adhesion molecules： adipocyte-derived plasma protein adiponectin. Circulation 100, 2473-2476.
Park, H.R., Shin, S.R., Han, A.L., Jeong, Y.J., 2015. The correlation between the triglyceride to high density lipoprotein cholesterol ratio and computed tomography- measured visceral fat and cardiovascular disease risk factors in local adult male subjects. Korean Journal of Family Medicine 36, 335-340.
Park, J.C., Yu, Y.B., Lee, J.H., Choi, J.S., Ok, K.D., 1996. Phenolic compounds from the rachis of Cedrelasinensis. Korean Journal of Pharmacognosy 27, 219-223.
Peck, P., 2010. "FDA Says It Will Review Pioglitazone Safety". MedPage Today.
Perocco, P., Bolognesi, S., Alberghini, W., 1983. Toxic activity of seventeen industrial solvents and halogenated compounds on human lymphocytes cultured in vitro. Toxicology Letters 16, 69-75.
Perry, L.I., 1980. Medical plants of east and south-east Asia： attributed properties and uses. Molecular Medicine.
Poon, S.L., Leu, S.F., Hsu, H.K., Liu, M.Y., Huang, B.M., 2005. Regulatory mechanism of Toona sinensis on mouse leydig cell steroidogenesis. Life Sciences 76, 1473-1487.
Ramsey, E., Sun, Q.B., Zhang, Z.Q., Zhang, C.M., Gou, W., 2009. Mini-Review： Green sustainable processes using supercritical fluid carbon dioxide. Journal of Environmental Sciences 21, 720-726.
Ramudu, S.K., Korivi, M., Kesireddy, M., Lee, L.C., Cheng, I.S., Kuo, C.H., Kesireddy, S.R, 2011. Nephro-protective effects of a ginger extract on cytosolic and mitochondrial enzymes against streptozotocin (STZ)-induced diabetic complications in rats. Chinese Journal of Physiology 54(2), 79-86.
Reaven, G.M., 1988. Role of insulin resistance in human disease. Diabetes 37, 1595-1607.
Reed, M.J., Meszaros, K., Entes, L.J., Claypool, M.D., Pinkett, J.G., Gadbois, T.M., eaven, G.M., 2000. A new rat model of type 2 siabetes： the fat-fed,streptozotocin-treated rat. Metabolism 49, 1390-1394.
Reifsnyder, P.C., Leiter, E.H., 2002. Deconstructing and reconstructing obesity-induced diabetes (diabesity) in mice. Diabetes 51, 825-832.
Reuter, T.Y., 2007. Diet-induced models for obesity and type 2 diabetes. Drug Discovery Today： Disease Models 4, 3-8.
Ritchie, S.A. and Connell, J.M.C., 2007. The link between abdominalobesity, metabolic syndrome and cardiovascular disease. Nutrition, Metabolism and Cardiovascular Diseases 17 (4), 319-326.
Rońyai, E., Simandi, B., Tomoskozi, S., Deak, A., Vigh, L., Weinbrenner, Z., 1998. Supercritical fluid extraction of corn germ with carbon dioxide-ethyl alcohol mixture. Journal of Supercritical Fluids 14, 75-81.
Rosa, E.D., Bartolucci, G.B., Brighenti, F., Gori, G.P., Sigon, M., Toffolo, D., 1985. The industrial use of solvents and risk of neuotoxicity. Annals of Occupational Hygiene 29, 391-397.
Rosenstock, J., Aggarwal, N., Polidori, D., Zhao, Y., Arbit, D., Usiskin, K., Capuano, G., Canovatchel, W., 2012. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with Type 2 diabetes. Diabetes Care 35, 1232-1238.
Sacks, F.M., Carey, V.J., Anderson, C.A., Miller, E.R.3rd., Copeland, T., Charleston, J., Harshfield, B.J., Laranjo, N., McCarron, P., Swain, J., White, K., Yee, K., Appel, L.J., 2014. Effects of high vs low glycemic index of dietary carbohydrate on cardiovascular disease risk factors and insulin sensitivity： the OmniCarb randomized clinical trial. Journal of the American Medical Association 312, 2531-2541.
Salazar, M.R., Carbajal, H.A., Espeche, W.G., Sisnieguez, C.E.L., Balbín, E., Dulbecco, C.A., Aizpurúa, M.A., Marillet, A.G., Reaven, G.M., 2012. Relation among the plasma triglyceride/high-density lipoprotein cholesterol concentration ratio, insulin resistance, and associated cardio-metabolic risk factors in men and women. American Journal of Cardiology 109, 1749-1753.
Shi, Y., Hu, F.B., 2014. The global implications of diabetes and cancer. The Lancet 383, 1947-1948.
Srinivasan, K., Ramarao, P., 2007. Animal models in type 2 diabetes research： an overview. Indian Journal of Medical Research 125, 451-472.
Srinivasan, K., Viswanad, B., Asrat, L., Kaul, C.L., Ramarao, P., 2005. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat： a model for type 2 diabetes and pharmacological screening. Pharmacological Research 52, 313-320.
Stumvoll, M., Goldstein, B.J., van Haeften, T.W., 2005. Type 2 diabetes： principles of pathogenesis and therapy. The Lancet 365, 1333-1346.
Tabish, S.A., 2007. Is diabetes becoming the biggest epidemic of the twenty-first century? International Journal of Health Sciences 1, V-VIII.
The IDF consensus worldwide definition of the metabolic syndrome, 2005, International Diabetes Federation, http://www.idf.org/metabolic-syndrome.
The national Institute of diabetes and digestive and kidney diseases (NIDDK), http://www.niddk.nih.gov/.
Torkelson, T.R., Oyen, F., McCollister, D.D., Rowe, V.K., 1958. Toxicity of 1, 1, 1-Trichloroethane as determined on laboratory animals and human subjects. American Industrial Hygiene Association Journal 19, 353-362.
Tu Youyou: how Mao’s challenge to malaria pioneer led to Nobel prize, 2015, The Guardian, http://www.theguardian.com/science/2015/oct/05.
US-FDA. United States - Food and Drug Administration, 2008. Available：US-FDA. United States-Food and Drug Administration, 2015. Available from：<http：//www.fda.gov/Drugs/DrugSafety/ucm459579.htm (accessed 08.28.15).
US-FDA. United States-Food and Drug Administration, 2015. Available from：<http：//www.fda.gov/Drugs/DrugSafety/ucm446845.htm> (accessed 05.15.15).
Van De Venter, M., Roux, S., Bungu, L.C., Louw, J., Crouch, N.R., Grace, O.M., Maharaj, V., Pillay, P., Sewnarian, P., Bhagwandin, N., Folb, P., 2008. Antidiabetic screening and scoring of 11 plants traditionally used in South Africa. Journal of Ethnopharmacology 119, 81-86.
Vos T, F.A.D., Naghavi, M., Lozano, R., Michaud, C., Ezzati, M., Shibuya, K., Salomon, J.A., Abdalla, S., Aboyans, V., Abraham, J., Ackerman, I., Aggarwal, R., Ahn, S.Y., Ali, M.K., Alvarado, M., Anderson, H.R., Anderson, L.M., Andrews, K.G., Atkinson, C., Baddour, L.M., Bahalim, A.N., Barker-Collo, S., Barrero, L.H., Bartels, D.H., Basáñez, M.G., Baxter, A., Bell, M.L., Benjamin, E.J., Bennett, D., Bernabé E, B.K., Bhandari, B., Bikbov, B., Bin, A.A., Birbeck, G., Black, J.A., Blencowe, H., Blore, J.D., Blyth, F., Bolliger, I., Bonaventure, A., Boufous, S., Bourne, R., Boussinesq, M., Braithwaite, T., Brayne, C., Bridgett, L., Brooker, S., Brooks, P., Brugha, T.S., Bryan-Hancock, C., Bucello, C., Buchbinder, R., Buckle, G., Budke, C.M., Burch, M., Burney, P., Burstein, R., Calabria, B., Campbell, B., Canter, C.E., Carabin, H., Carapetis, J., Carmona, L., Cella, C., Charlson, F., Chen, H., Cheng, A.T., Chou, D., Chugh, S.S., Coffeng, L.E., Colan, S.D., Colquhoun, S., Colson, K.E., Condon, J., Connor, M.D., Cooper, L.T., Corriere, M., Cortinovis, M., de Vaccaro, K.C., Couser, W., Cowie, B.C., Criqui, M.H., Cross, M., Dabhadkar, K.C., Dahiya, M., Dahodwala, N., Damsere-Derry, J., Danaei, G., Davis, A., De Leo, D., Degenhardt, L., Dellavalle, R., Delossantos, A., Denenberg, J., Derrett, S., Des Jarlais, D.C., Dharmaratne, S.D., Dherani, M., Diaz-Torne, C., Dolk, H., Dorsey, E.R., Driscoll, T., Duber, H., Ebel, B., Edmond, K., Elbaz, A., Ali, S.E., Erskine, H., Erwin, P.J., Espindola, P., Ewoigbokhan, S.E,. Farzadfar, F., Feigin, V., Felson, D.T., Ferrari, A., Ferri, C.P., Fèvre, E.M., Finucane, M.M., Flaxman, S., Flood, L., Foreman, K., Forouzanfar, M.H., Fowkes, F.G., Franklin, R., Fransen, M., Freeman, M.K., Gabbe, B.J., Gabriel, S.E., Gakidou, E., Ganatra, H.A., Garcia, B., Gaspari, F., Gillum, R.F., Gmel, G., Gosselin, R., Grainger, R., Groeger, J., Guillemin, F., Gunnell, D., Gupta, R., Haagsma, J., Hagan, H., Halasa, Y.A., Hall, W., Haring, D., Haro, J.M., Harrison, J.E., Havmoeller, R., Hay, R.J., Higashi, H., Hill, C., Hoen, B., Hoffman, H., Hotez, P.J., Hoy, D., Huang, J.J., Ibeanusi, S.E., Jacobsen, K.H., James, S.L., Jarvis, D., Jasrasaria, R., Jayaraman, S., Johns, N., Jonas, J.B., Karthikeyan, G., Kassebaum, N., Kawakami, N., Keren, A., Khoo, J.P., King, C.H., Knowlton, L.M., Kobusingye, O., Koranteng, A., Krishnamurthi, R., Lalloo, R., Laslett, L.L., Lathlean, T., Leasher, J.L., Lee, Y.Y., Leigh, J., Lim, S.S., Limb, E., Lin, J.K., Lipnick, M., Lipshultz, S.E., Liu, W., Loane, M., Ohno, S.L., Lyons, R., Ma, J., Mabweijano, J., MacIntyre, M.F., Malekzadeh, R., Mallinger, L., Manivannan, S., Marcenes, W., March, L., Margolis, D.J., Marks, G.B., Marks, R., Matsumori, A., Matzopoulos, R., Mayosi, B.M., McAnulty, J.H., McDermott, M.M., McGill, N., McGrath, J., Medina-Mora, M.E., Meltzer, M., Mensah, G.A., Merriman, T.R., Meyer, A.C., Miglioli, V., Miller, M., Miller, T.R., Mitchell, P.B., Mocumbi, A.O., Moffitt, T.E., Mokdad, A.A,. Monasta, L., Montico, M., Moradi-Lakeh, M., Moran, A., Morawska, L., Mori, R., Murdoch, M.E., Mwaniki, M.K., Naidoo, K., Nair, M.N., Naldi, L., Narayan, K.M., Nelson, P.K., Nelson, R.G., Nevitt, M.C., Newton, C.R., Nolte, S., Norman, P., Norman, R., O''Donnell, M., O''Hanlon, S., Olives, C., Omer, S.B., Ortblad, K., Osborne, R., Ozgediz, D., Page, A., Pahari, B., Pandian, J.D., Rivero, A.P., Patten, S.B., Pearce, N., Padilla, R.P., Perez-Ruiz, F., Perico, N., Pesudovs, K., Phillips, D., Phillips, M.R., Pierce, K., Pion, S., Polanczyk, G.V., Polinder, S., Pope, C.A.3rd, Popova, S., Porrini, E., Pourmalek, F., Prince, M., Pullan, R.L., Ramaiah, K.D., Ranganathan, D., Razavi, H., Regan, M., Rehm, J.T., Rein, D.B., Remuzzi, G., Richardson, K., Rivara, F.P., Roberts, T., Robinson, C., De Leòn, F.R., Ronfani, L., Room, R., Rosenfeld, L.C., Rushton, L., Sacco, R.L., Saha, S., Sampson, U., Sanchez-Riera, L., Sanman, E., Schwebel, D.C., Scott, J.G., Segui-Gomez, M., Shahraz, S., Shepard, D.S., Shin, H., Shivakoti, R., Singh, D., Singh, G.M., Singh, J.A., Singleton, J., Sleet, D.A., Sliwa, K., Smith, E., Smith, J.L., Stapelberg, N.J., Steer, A., Steiner, T., Stolk, W.A., Stovner, L.J., Sudfeld, C., Syed, S., Tamburlini, G., Tavakkoli, M., Taylor, H.R., Taylor, J.A., Taylor, W.J., Thomas, B., Thomson, W.M., Thurston, G.D., Tleyjeh, I.M., Tonelli, M., Towbin, J.A., Truelsen, T., Tsilimbaris, M.K., Ubeda, C., Undurraga, E.A., van der Werf, M.J., van Os, J., Vavilala, M.S., Venketasubramanian, N., Wang, M., Wang, W., Watt, K., Weatherall, D.J., Weinstock, M.A., Weintraub, R., Weisskopf, M.G., Weissman, M.M., White, R.A., Whiteford, H., Wiersma, S.T., Wilkinson, J.D., Williams, H.C., Williams, S.R., Witt, E., Wolfe, F., Woolf, A.D., Wulf, S., Yeh, P.H., Zaidi, A.K., Zheng, Z.J., Zonies, D., Lopez, A.D., Murray, C.J., AlMazroa, M.A., Memish, Z.A., 2012. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010： a systematic analysis for the global burden of disease study 2010. The Lancet 380, 2163-2196.
Wang, C.Y., Lin, K.H., Yang, C.J., Tsai, J.R., Hung, J.Y., Wang, P.H., Hsu, H.K., Huang, M.S., 2010. Toona sinensis extracts induced cell cycle arrest and apoptosis in the human lung large cell carcinoma. Kaohsiung Journal of Medical Sciences 26, 68-75.
Wang, J.S., Sheaff, C.N., Yoon, B.H., Assleman, R.S., Wai, C.M., 2009. Extraction of uranium from aqueous solutions by using ionic liquid and supercritical carbon dioxide in conjunction. Chemistry-A European Journal 15, 4458-4463.
Wang, L.J., Weller, C.L., 2006. Recent advances in extraction of natural products from plants. Trends in Food Science and Technology 17, 300-312.
Wang, L.J., Weller, C.L., 2008. Supercritical CO2 extraction of lipids from grain sorghum dried distillers grains with soluble. Bioresource Technology 99, 1373-1382.
Wang, P.H., 2000. The study of hypoglycemic effects of Toona sinensis aqueous leaf extracts on Alloxan-induced diabetic rats. Master thesis, Kaohsiung Medical University Graduate Institute of Medicine. Kaohsiung, Taiwan.
Wang, P.H., Tsai, M.J., Hsu, C.Y., Wang, C.Y., Hsu, H.K., Weng, C.F., 2008. Toona sinensis Roem (Meliaceae) leaf extract alleviates hyperglycemia via altering adipose glucose transporter 4. Food and Chemical Toxicology 46, 2554-2560.
Watson, R.T., Jeffrey, E., Pessin, J.E., 2007. GLUT4 translocation： the last 200 nanometers. Cellular Signalling 19, 2209-2217.
What is a Botanical Drug? 2015, U.S. Food and Drug Administration, http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm090983.htm.
Wilding, J.P., Norwood, P., T''joen, C., Bastien, A., List, J.F., Fiedorek, F.T., 2009. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers. Diabetes Care 32, 1656-1662.
World Health Organization (WHO), http：//www.who.int/en/
Yang, F.Y., 2003. Study on the physiological function of Toona sinensis Roem in human spermatozoa. Master Thesis, National Cheng Kung University, Tainan, Taiwan.
Yang, H.L., Chang, W.H., Chia, Y.C., Huang, C.J., Lu, F.J., Hsu, H.K., Hseu, Y.C., 2006. Toona sinensis extracts induces apoptosis via reactive oxygen species in human premyelocytic leukemia cells. Food and Chemical Toxicology 44, 1978-1988.
Yang, W.S., Jeng, C.Y., Wu, T.J., Tanaka, S., Funahashi, T., Matsuzawa, Y., Wang, J.P., Chen, C.L., Tai, T.Y., Chuang, L.M., 2002b. Synthetic peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Diabetes Care 25, 376-380.
Yang, W.S., Lee, W.J., Funahashi, T., Tanaka, S., Matsuzawa, Y., Chao, C.L., Chen, C.L., Tai, T.Y., Chuang, L.M., 2001. Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. Journal of Clinical Endocrinology and Metabolism 86, 3815-3819.
Yang, W.S., Lee, W.J., Funahashi, T., Tanaka, S., Matsuzawa, Y., Chao, C.L., Chen, C.L., Tai, T.Y., Chuang, L.M., 2002a. Plasma adiponectin levels in overweight and obese Asians. Obesity research 10, 1104-1110.
Yang, Y.C., Hsu, H.K., Hwang, J.H., Hong, S.J., 2003. Enhancement of glucose uptake in 3T3-L1 adipocytes by Toona sinensis leaf extract. Kaohsiung Journal of Medical Sciences 19, 327-333.
Yuhki, K.I., Kawabe, J.I., Ushikubi, F., 2005. Fat, keeping the heart healthy? Nature Medicine 11, 1048-1049.
Zhang, K., Luo, N., Xu, X.J., Xu, X.N., 2008. Sustainable development models of converting cropland to forest in Dabieshan District, Anhui Province. Frontiers of Forestry in China 3, 92-97.
Zhang, L., Feng, Y., List, J., Kasichayanula, S., Pfister, M., 2010. Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus： effects on glycaemic control and body weight. Diabetes, Obesity and Metabolism 12, 510-516.
Zhou, M., Xu, H., Pan, L., Wen, J., Liao, W., Chen, K., 2008. Rosiglitazone promotes atherosclerotic plaque stability in fat-fed ApoE-knockout mice. European Journal of Pharmacology 590, 297-302.
Zitkus, B.S., 2014. Update on the American diabetes association standards of medical care. Nurse Practitioner 39, 22-32.
Zou, C., Shen, Z., 2007. An optimized in vitro assay for screening compounds thatstimulate liver cell glucose utilization with low cytotoxicity. Journal of Pharmacological and Toxicological Methods 56, 58-62.
胡湘湘，天然藥物技轉商機 搶攻全球新藥市場，工業技術與資訊月刊276期2014年10月號，工業技術研究院，新竹縣。
本校中草藥研究團隊受華人榮獲諾貝爾獎鼓舞激勵, 2015, 中國醫藥大學電子報, http://www2.cmu.edu.tw/~cmcrdc/epaper/detail.php?ep
aperno= 68&class=A&id=322.
康銘仁，2014，香椿萃取物改善胰島素阻抗及抑制脂肪細胞內單房大油滴形成之作用機轉探討，高雄醫學大學基因體醫學科碩士班碩士論文。
經濟部技術處，2013醫藥產業年鑑，經濟部技術處產業技術知識服務計畫專案辦公室出版，台北市。
廖敏淳，2011，綠色製程香椿萃取物的抗糖尿病效果及藥理機轉探討，高雄醫學大學醫學遺傳學科碩士班碩士論文。