肥胖易造成胰島素阻抗的形成，進而引起高血糖、高血脂、高血壓等症狀，研究指出，thiazolidinedione ( TZD )類藥物可活化過氧化小體增生活化受體 ( peroxisome proliferator activated receptor gamma, PPARγ )以增加胰島素敏感性來降低血糖。香椿 ( Toona sinesis Roem ) 具有調節血糖的功效，但其降血糖作用與PPARγ基因表現與活化的關聯則未明。因此，本研究先製備不同醇水比例的香椿葉 ( Toona sinesis leaves, TSL ) 萃取物 ( TSL-E1 ~ TSL-E6)，再利用細胞模式及高血糖動物探討這些萃取物對 PPARγ 基因的影響。
本研究主要先以PPARγ-LBD ( ligand binding domain ) luciferase assay篩選不同香椿萃取物活化PPARγ基因的能力；再以3T3-L1脂肪前驅細胞模式分析香椿萃取物對細胞內之脂肪形成以及對PPARγ蛋白質表現的影響。由細胞實驗的結果，篩選出具有最佳活性效果的萃取物，繼續利用高脂飼料 ( High fat diet, HFD; 54 % energy by fat ) 誘發的C57BL/6高血糖小鼠模式，連續八週餵食不同劑量之香椿萃取物與pioglitazone ( PIO )，觀察萃取物調節血糖、血脂之效果，及對脂肪組織 PPARγ 基因表現的影響。同時，運用高效液能層析儀 ( HPLC ) 及液相層析質譜儀 (LC-MS ) 分離萃取物中主要成分，並進一步以脂肪前驅細胞偵測PPAR PPARγ 基因表現，探討香椿萃取物活化PPARγ的有效成份。
PPARγ-LBD luciferase assay測試六種香椿萃取物顯示，其中三種 （TSL-E4, TSL-E5, TSL-E6）可顯著活化PPARγ；而TSL-E4, TSL-E6可防止3T3-L1脂肪前驅細胞的油滴堆積現象，並增加PPARγ mRNA與蛋白質的表現量；此外，TSL-E6亦可活化PPARγ下游的 fatty acid binding proteins（aP2）基因表現。
高血糖小鼠連續兩週餵食TSL-E6（2 g/kg）後開始產生降血糖的作用，尤其在餵食第四週時達到最佳的降血糖效果。此外， 餵食TSL-E6（2 g/kg）至第八週時，小鼠體重較高脂飼料組為低，且脂肪組織PPARγ基因、蛋白以及aP2基因表現均較高脂飼料組為高。利用HPLC及LC-MS鑑定TSL-E6萃取物成份，發現主要為gallic acid，ethyl gallate，以及methylgallate等3種物質，其中gallic acid含量最高，且可增加脂肪前驅細胞PPARγ基因表現。因此，gallic acid 可能為TSL-E6中活化PPARγ的主要活性成分。
綜合以上結果，我們發現多種香椿萃取物均可活化PPARγ基因，但以TSL-E6的作用最佳。細胞與動物模式的結果顯示，TSL-E6可增加PPARγ mRNA與蛋白質表現，減少脂肪細胞之油滴堆積，具有調節動物血糖與抑制體重增加的效果，gallic acid可能為其主要活性成分。因此，TSL-E6的成份可能與PPARγ ligand的作用相似，可參與調節PPARγ基因表現與血糖的作用，未來可進一步研究TSL-E6調節PPARγ表現之分子機制與應用價值。

Obesity which is associated with insulin resistance was thought to result in hyperglycemia, hypertension, hyperlipidemia and other health problems. Previous studies indicated that thiazolidinedione (TZD) compounds, such as pioglitazone (PIO), increased the insulin-sensitivity and exibibited hypoglycemic effects via the activation of peroxisome proliferator-activated receptor gamma (PPARγ). Toona sinensis Roem leaves (TSL) extracts were documented to exert the hypoglycemic effect, however, the mechanisms underlying and its relationship to the PPARγ is still unknown. In this study, different TSL extracts prepared by series of ethanol/water were used to examine their PPARγ activities using PPARγ-LBD（ligand binding doman）luciferase expression system in HepG2 cell line. Meanwhile, adigogenesis, PPARγ gene expression, and hypoglycemic effect of TSL extracts were also investigated using both 3T3-L1 preadipocytes cell model and high fat diet (HFD, 54 % energy by fat) induced hyperglycemic C57BL/6 mice model. The active compounds in TSL extracts were identified using HPLC and LC-MS analysis, and further confirmed by PPARγ gene expression in 3T3-L1 cells for PPARγ activation.
The PPARγ-LBD luciferase assay indicated that TSL-E4, TSL-E5 and TSL-E6 were the candidates of PPARγ ligands. Moreover, the analysis of Oil red O stain showed that the treatment of TSL-E4 and TSL-E6 suppressed the lipid accumulation in adipocytes. The TSL-E6 treatment significantly increased the PPARγ gene and protein expressions and its downstream aP2 gene expression in adipocytes. The hypoglycemic effect of TSL-E6 in animal model was occurred at second weeks and reached peak at fourth weeks. The body weights gain of TSL-E6 group were significantly lowerd than that of HFD group after 8 weeks of TSL-E6 feeding. The PPARγ gene and protein expressions, and its downstream aP2 gene expression were elevated in the adipose tissue of hyperglycemic mice with TSL-E6 treatment for 8 weeks. The analysis of HPLC and LC-MS identified that gallic acid, ethyl gallate and methyl gallate were the major compounds in TSL-E6. Gallic acid increased the PPARγ gene expression in 3T3-L1 cells, indicating that gallic acid is the possible active compound in TSL-E6 for PPARγ activation.
In conclusion, the TSL-E6 is the most effective PPARγ activator in our TSL serious extracts. Both in cell and animal models, the TSL-E6 treatment increased the PPARγ gene and protein expressions. Moreover, the TSL-E6 treatment suppressed the lipid accumulation in 3T3-L1 adipocytes. The TSL-E6 treatment decreased the blood glucose level, and prevented the weight gain in the hyperglycemia mice. Our results suggested that TSL-E6 might be the PPARγ ligand, which is involved in the regulation of glucose homeostasis. Gallic acid may be the possible active compound in TSL-E6. The molecular mechanism and applications of TSL-E6 on the PPARγ-related regulation can be further studied.

Akazawa S, Sun F, Ito M, Kawasaki E, Eguchi K. Efficacy of troglitazone on body fat distribution in type 2 diabetes. Diabetes care. 2000, 23:1067-1071.
Arimura N, Horiba T, Imagawa M, Shimizu M, Sato R. The peroxisome proliferator-activated receptor gamma regulates expression of the perilipin gene in adipocytes. The Journal of Biological Chemistry. 2004, 279:10070-10076.
Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, Balas B, Gastaldelli A, Tio F, Pulcini J, Berria R, Ma JZ, Dwivedi S, Havranek R, Fincke C, DeFronzo R, Bannayan GA, Schenker S, Cusi K. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. The New England Journal of Medicine. 2006, 355:2297-2307.
Berger J, Moller DE. The mechanisms of action of PPARs. Annual Review of Medicine. 2002, 53: 409-435.
Bogacka I, Xie H, Bray GA, Smith SR. The effect of pioglitazone on peroxisome proliferator-activated receptor-gamma target genes related to lipid storage in vivo. Diabetes Care. 2004, 27:1660-1667.
Chang H.C., C.H. Yeh, M.S. Huang, C. Hsu H.K. Hsu. ( 2001 ) : 香椿萃取液減少Bcl-2 蛋白質表現而促進H520 肺癌細胞自然凋亡。Health food society of Taiwan. Feb.30.
Chang HC, Hung WC, Huang MS, Hsu HK: Extract from the leaves of Toona sinensis exerts potent antiproliferative effect on human lung cancer cells. American Journal of Chinese Medicine. 2002, 30: 307-314.
Chang HL, Hsu HK, Su JH, Wang PH, Chung YF,Chia YC, Tsai LY, Wu YC, Yuan. SS. The fractionated Toona sinensis leaf extract induces apoptosis of human ovarian cancer cells and inhibits tumor growth in a murine xenograft model. Gynecologic Oncology. 2006, 102: 309–314
Chao CY, Huang CJ. Bitter gourd (Momordica charantia) extract activates peroxisome proliferator-activated receptors and upregulates the expression of the acyl CoA oxidase gene in H4IIEC3 hepatoma cells. Journal of Biomedical Science. 2003, 10:782-791.
Chawla A, Schwarz EJ, Dimaculangan DD, Lazar MA. Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology. 1994, 135: 798-800.
Chen WI, Chen YR, Wang PH, Lue SI, Hsu HK. ( 2002 ) : 椿葉萃取物對血小板凝集的作用。Health food society of Taiwan. Feb. 70.
Chiu NY, Technician, Chang KH: Toona sinensis ( A.Juss ) Roem. In the illustrated medicinal plants of Taiwan, SMC publishing Inc Taiwan ROC 1995, 1: 131-132.
Choi I, Park Y, Choi H, Lee E.H. Anti-adipogenic activity of rutin in 3T3-L1 cells and mice fed with high-fat diet. Biofactors. 2006, 26:273-281.
Clarke SL, Robinson CE, Gimble JM. CAAT/enhancer binding proteins directly modulate transcription from the peroxisome proliferator-activated receptor gamma 2 promoter. Biochemical and Biophysical Research Communications. 1997, 240: 99-103.
Cobb JE, Blanchard SG, Boswell EG, Brown KK, Charifson PS, Cooper JP, Collins JL, Dezube M, Henke BR, Hull-Ryde EA, Lake DH, Lenhard JM, Oliver W Jr, Oplinger J, Pentti M, Parks DJ, Plunket KD, Tong WQ. N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 3. Structure-activity relationship and optimization of the N-aryl substituent. Journal of Medicinal Chemistry. 1998, 41:5055-5069.
Dang ZC, Audinot V, Papapoulos SE, Boutin JA, Löwik CW. Peroxisome Proliferator-activated Receptor γ (PPARγ) as a Molecular Target for the Soy Phytoestrogen Genistein. Journal of Biological Chemistry. 2003; 278: 962 – 967.
Després JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006, 444:881-7.
El-Jack AK, Hamm JK, Pilch PF, Farmer SR. Reconstitution of insulin-sensitive glucose transport in fibroblasts requires expression of both PPARgamma and C/EBPalpha. Journal of Biological Chemistry. 1999,274:7946-7951.
Edmonds JM, Staniforth M: Toona Sinensis (Meliaceae). Curtis's Botanical Magazine 1998, 15: 186-193.
Fu J, Oveisi F, Gaetani S, Lin E, Piomelli D. Oleoylethanolamide, an endogenous PPAR-alpha agonist, lowers body weight and hyperlipidemia in obese rats. Neuropharmacology. 2005, 48:1147-1153.
Gallou-Kabani C, Vigé A, Gross MS, Rabès JP, Boileau C, Larue-Achagiotis C, Tomé D, Jais JP, Junien C. C57BL/6J and A/J mice fed a high-fat diet delineate components of metabolic syndrome. Obesity (Silver Spring, Md.). 2007, 15:1996-2005.
Gamarallage VK, Senanayake, Mitsuru Maruyamaa, Kei Shibuya. PPARγ Ligand- Binding Activity Affects Diabetes in KK-Ay Mice, Abdominal Obesity in Diet- Induced Obese C57BL Mice and Hypertension in Spontaneously Hypertensive Rats. Journal of Nutrition. 2003,133: 3369-3377.
Gillies PS, Dunn CJ. Pioglitazone. Drug. 200, 60: 333-343.
Gloerich J, van Vlies N, Jansen GA, Denis S, Ruiter JP, van Werkhoven MA, Duran M, Vaz FM, Wanders RJ, Ferdinandusse S. A phytol-enriched diet induces changes in fatty acid metabolism in mice both via PPARalpha-dependent and independent pathways. Journal of Lipid Research. 2005,46:716-726.
Goto T, Takahashi N, Kato S, Egawa K, Ebisu S, Moriyama T, Fushiki T, Kawada T. Phytol directly activates peroxisome proliferator-activated receptor alpha (PPARalpha) and regulates gene expression involved in lipid metabolism in PPARalpha-expressing HepG2 hepatocytes. Biochemical and Biophysical Research Communications. 2005, 337: 440-445.
Gurnell M. PPARgamma and metabolism: insights from the study of human genetic variants. Clinical Endocrinology. 2003, 59:267-277.
Hallakou S, Doaré L, Foufelle F, Kergoat M, Guerre-Millo M, Berthault MF, Dugail I, Morin J, Auwerx J, Ferré P. Pioglitazone induces in vivo adipocyte differentiation in the obese Zucker fa/fa rat. Diabetes. 1997,46:1393–1399.
Harrison SA, Day CP. Benefits of lifestyle modification in NAFLD. Gut. 2007 56:1760-1769.
Hsieh TJ, Liu TZ, Chia YC, Chern CL, Lu FJ, Chuang MC, Mau SY, Chen SH, Syu YH, Chen CH. 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 .2004, 42: 843-850.
Hsu HK, Yang YC, Hwang JH, Hong SJ. Effects of Toona sinensis leaf extract on lipolysis in differentiated 3T3-L1 adipocytes. The Kaohsiung Journal of Medical Sciences. 2003, 19: 385-390.
Huang TH, Kota BP, Razmovski V, Roufogalis BD. Herbal or natural medicines as modulators of peroxisome proliferator-activated receptors and related nuclear receptors for therapy of metabolic syndrome. Basic & Clinical Pharmacology & Toxicology. 2005, 96:3-14.
Huang TH, Peng G, Kota BP, Li GQ, Yamahara J, Roufogalis BD, Li Y. Anti-diabetic action of Punica granatum flower extract: activation of PPAR-gamma and identification of an active component. Toxicology and Applied Pharmacology. 2005, 207: 160-169.
Huang YH, Lee TH, Chan KJ, Hsu FL, Wu YC and Lee MH. Anemonin is a natural bioactive compound that can regulate tyrosinase-related proteins and mRNA in human melanocytes. Journal of Dermatological Science. 2008, 49: 115-123.
International Agency for Research on Cancer, World Health Organization: Weight control and physical activity. In: Vainio H, Bianchini F, eds. International Agency for Research on Cancer handbooks of cancer prevention. Vol 6. Lyon, France: IARC Press, 2002.
Jayasooriya AP, Sakono M, Yukizaki C, Kawano M, Yamamoto K, Fukuda N. Effects of Momordica charantia powder on serum glucose levels and various lipid parameters in rats fed with cholesterol-free and cholesterol-enriched diets. Journal of Ethnopharmacology. 2000, 72:331-336.
Jennifer M, Edmonds, Martin S: TOONA SINENSIS. Bentham-Moxon Trust. 1998, 186-196.
Kawasaki F, Matsuda M, Kanda Y, Inoue H, Kaku K. Structural and functional analysis of pancreatic islets preserved by pioglitazone in db/db mice. American Journal of Physiology. Endocrinology and Metabolism. 2005, 288:E510-518.
Kim JB, Spiegelman BM. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes & Development. 1996, 10:1096-1107.
Kim MJ, Chang UJ, Lee JS. Inhibitory effects of Fucoidan in 3T3-L1 adipocyte differentiation. Marine Biotechnology. 2009, 11: 557–562.
Kim NH, Choi SK, Kim SJ, Moon PD, Lim HS, Choi IY, Na HJ, An HJ, Myung NY, Jeong HJ, Um JY, Hong SH, Kim HM. Green tea seed oil reduces weight gain in C57BL/6J mice and influences adipocyte differentiation by suppressing peroxisome proliferator-activated receptor-gamma. Pflügers Archiv European Journal of Physiology. 2008, 457:293-302.
Kletzien RF, Clarke SD, Ulrich RG. Enhancement of adipocyte differentiation by an insulin-sensitizing agent. Molecular Pharmacology. 1992, 41:393-398.
Kuroda M, Mimaki Y, Sashida Y, Mae T, Kishida H, Nishiyama T, Tsukagawa M, Konishi E, Takahashi K, Kawada T, Nakagawa K, Kitahara M. Phenolics with PPAR-gamma ligand-binding activity obtained from licorice (Glycyrrhiza uralensis roots) and ameliorative effects of glycyrin on genetically diabetic KK-A(y) mice. Bioorganic & Medicinal Chemistry Letters. 2003, 13:4267-4272.
Lee MH, Lin YP, Hsu FL, Zhan GR, Yen KY. Bioactive constituents of Spatholobus suberectus in regulating tyrosinase-related proteins and mRNA in HEMn cells. Phytochemistry. 2006, 67: 1262-1270.
Liao JW, Hsu CK, Wang MF, Hsu WM, Chan YC. Beneficial effect of Toona sinensis Roemor on improving cognitive performance and brain degeneration in senescence-accelerated mice. The British Journal of Nutrition. 2006, 96:400-407.
Liao W, Nguyen MT, Yoshizaki T, Favelyukis S, Patsouris D, Imamura T, Verma IM, Olefsky JM. Suppression of PPAR-gamma attenuates insulin-stimulated glucose uptake by affecting both GLUT1 and GLUT4 in 3T3-L1 adipocytes. American Journal of Physiology. Endocrinology and Metabolism. 2007, 293:E219-227.
Martin G, Schoonjans K, Lefebvre AM, Staels B, Auwerx J. Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARalpha and PPARgamma activators. Journal of Biological Chemistry. 1997, 272: 28210-28217.
Mae T, Kishida H, Nishiyama T, Tsukagawa M, Konishi E, Kuroda M, Mimaki Y, Sashida Y, Takahashi K, Kawada T, Nakagawa K, Kitahara M. A licorice ethanolic extract with peroxisome proliferator-activated receptor-gamma ligand-binding activity affects diabetes in KK-Ay mice, abdominal obesity in diet-induced obese C57BL mice and hypertension in spontaneously hypertensive rats. Journal of Nutrition. 2003, 133: 3369-3377.
Miura T, Itoh Y, Iwamoto N, Kato M, Ishida T. Suppressive activity of the fruit of Momordica charantia with exercise on blood glucose in type 2 diabetic mice. Biological & Pharmaceutical Bulletin. 2004, 27: 248-250.
Miyazaki Y, Mahankali A, Matsuda M, Mahankali S, Hardies J, Cusi K, Mandarino LJ, DeFronzo RA. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. Journal of Clinical Endocrinology and Metabolism. 2002, 87: 2784-2791
Mokdad A.H., Ford E.S., Bowman B.A., Dietz W.H., Vinicor F., Bales V.S., Marks J.S. Prevalence of Obesity, Diabetes, and Obesity-Related Health Risk Factors, 2001. Journal of American Medical Association. 2003, 289: 76-79.
Morikawa K., Ikeda C., Nonaka M., Suzuki I. Growth arrest and apoptosis induced by quercetin is not linked to adipogenic conversion of human preadipocytes. Metabolism. 2007, 56: 1656-1665.
Murase Y, Kobayashi J, Nohara A, Asano A, Yamaaki N, Suzuki K, Sato H, Mabuchi H. Raloxifene promotes adipocyte differentiation of 3T3-L1 cells. European Journal of Pharmacology. 2006, 538: 1-4.
Ntambi J.M., Young-Cheul K. Adipocyte differentiation and gene expression. Journal of Nutrition. 2000, 130: 3122S-3126S.
Okuno A, Tamemoto H, Tobe K, Ueki K, Mori Y, Iwamoto K, Umesono K, Akanuma Y, Fujiwara T, Horikoshi H, Yazaki Y, Kadowaki T. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. Journal of Clinical Investigation. 1998, 101:1354-1361.
Pan WH, Flegal KM, Chang HY, Yeh WT, Yeh CJ, Lee WC. Body mass index and obesity-related metabolic disorders in Taiwanese and US whites and blacks: implications for definitions of overweight and obesity for Asians. American Journal of Clinical Nutrition. 2004, 79: 31-39.
Park JC, Yu YB Yu, Lee JH, Chol JS, Ok KD. Phenolic Compounds from the Rachis of Cedrela sinensis. Korea Journal of Pharmacognosy. 1996, 27: 219-223.
Park MY, Lee KS, Sung MK. Effects of dietary mulberry, Korean red ginseng, and banaba on glucose homeostasis in relation to PPAR-alpha, PPAR-gamma, and LPL mRNA expressions. Life Sciences. 2005, 77: 3344 -3354.
Prasad CN, Anjana T, Banerji A, Gopalakrishnapillai A. Gallic acid induces GLUT4 translocation and glucose uptake activity in 3T3-L1 cells. FEBS Letters. 2010, 584:531-536.
Reaven G.M: Role of insulin resistance in human disease. Diabetes. 1988, 37: 1595-1607.
Rival Y, Stennevin A, Puech L, Rouquette A, Cathala C, Lestienne F, Dupont-Passelaigue E, Patoiseau JF, Wurch T, Junquéro D. Human adipocyte fatty acid-binding protein (aP2) gene promoter-driven reporter assay discriminates nonlipogenic peroxisome proliferator-activated receptor gamma ligands. Journal of Pharmacology and Experimental Therapeutics. 2004, 311:467-475.
Ruimin Mu, Xiangrong Wang, Sixiu Liu, Xueliang Yuan, Shoubing Wang, Zhengqiu Fan. Rapid determination of volatile compounds in Toona sinensis (A. Juss.) Roem. by MAE-HS-SPME followed by GC-MS. Chromatographia. 2007, 65: 463-467.
Schlüter A, Yubero P, Iglesias R, Giralt M, Villarroya F. The chlorophyll-derived metabolite phytanic acid induces white adipocyte differentiation. International Journal of Obesity and Related Metabolic Disorders . 2002, 26:1277-1280.
Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, Heyman R, Briggs M, Deeb S, Staels B, Auwerx J: PPARα and PPARγ activators direct a tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. The EMBO Journal.1996, 15:5336-5348.
Senanayake GV, Maruyama M, Shibuya K, Sakono M, Fukuda N, Morishita T, Yukizaki C, Kawano M, Ohta H. The effects of bitter melon (Momordica charantia) on serum and liver triglyceride levels in rats. Journal of Ethnopharmacology. 2004, 91:257-262.
Sfeir Z, Ibrahimi A, Amri E, Grimaldi P, Abumrad N. Regulation of FAT/CD36 gene expression: further evidence in support of a role of the protein in fatty acid binding/transport. Prostaglandins, Leukotrienes, and Essential Fatty Acids. 1997, 57:17-21.
Shao D, Lazar MA. Peroxisome proliferator activated receptor gamma, CCAAT/enhancer-binding protein alpha, and cell cycle status regulate the commitment to adipocyte differentiation. Journal of Biological Chemistry. 1997, 272:21473-21478.
Shen P, Liu M.H, Ng T.Y., Chan Y.H., Yong E.L. Differential effects of isoflavones, from Astragalus membranaceus and Pueraria thomsonii, on the activation of PPARalpha, PPARgamma, and adipocyte differentiation in vitro. The Journal of Nutrition. 2006, 136:899-905.
Shimabukuro M, Zhou YT, Levi M, Unger RH. Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes.. Proceedings of the National Academy of Sciences of the United States of America. 1998, 95:2498-2502.
Shin DW, Kim SN, Lee SM, Lee W, Song MJ, Park SM, Lee TR, Baik JH, Kim HK, Hong JH, Noh M. (-)-Catechin promotes adipocyte differentiation in human bone marrow mesenchymal stem cells through PPAR gamma transactivation. Biochemical Pharmacology. 2009, 77:125-133.
Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature. 2001, 409: 307–312.
Takada J, Fonseca-Alaniz MH, de Campos TB, Andreotti S, Campana AB, Okamoto M, Borges-Silva CN, Machado UF, Lima FB. Metabolic recovery of adipose tissue is associated with improvement in insulin resistance in a model of experimental diabetes. Journal of Endocrinology. 2008, 198:51-60.
Takahashi N, Kawada T, Goto T, Yamamoto T, Taimatsu A, Matsui N, Kimura K,Saito M, Hosokawa M, Miyashita K, Fushiki T. Dual action of isoprenols from herbal medicines on both PPARγ and PPARα in 3T3-L1 adipocytes and HepG2 hepatocytes. FEBS Letters.2002, 54:315-322.
The DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. The Lancet. 2006, 368: 1096-1105.
Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994, 79:1147-1156.
Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM. mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes & Development. 1994, 8:1224-1234.
Wang PH, Tsai MJ, Hsu CY, Wang CY, Hsu HK, Weng CF. Toona sinensis Roem (Meliaceae) leaf extract alleviates hyperglycemia via altering adipose glucose transporter 4. Food and Chemical Toxicology. 2008, 46:2554-2560.
Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. Journal of Medicinal Chemistry. 2000, 43:527-550.
Wu Z, Xie Y, Morrison RF, Bucher NL, Farmer SR. PPARgamma induces the insulin-dependent glucose transporter GLUT4 in the absence of C/EBPalpha during the conversion of 3T3 fibroblasts into adipocytes. Journal of Clinical Investigation. 1998, 101:22-32.
Wu Z, Rosen ED, Brun R, Hauser S, Adelmant G, Troy AE, McKeon C, Darlington GJ, Spiegelman BM. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Molecular Cell. 1999, 3:151-158.
Yajima H, Ikeshima E, Shiraki M, Kanaya T, Fujiwara D, Odai H, Tsuboyama- Kasaoka N, Ezaki O, Oikawa S, Kondo K. Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor alpha and gamma and reduce insulin resistance. Journal of Biological Chemistry. 2004, 279:33456-33462.
Yang B, Lin P, Carrick KM, McNulty JA, Clifton LG, Winegar DA, Strum JC, Stimpson SA, Pahel GL. PPARgamma agonists diminish serum VEGF elevation in diet-induced insulin resistant SD rats and ZDF rats. Biochemical and Biophysical Research Communications. 2005, 334:176-182.
Yang B, Brown KK, Chen L, Carrick KM, Clifton LG, McNulty JA, Winegar DA, Strum JC, Stimpson SA, Pahel GL. Serum adiponectin as a biomarker for in vivo PPARgamma activation and PPARgamma agonist-induced efficacy on insulin sensitization/lipid lowering in rats. MC Pharmacology. 2004, 4.
Yang CJ, Huang YJ, Wang CY, Wang PH, Hsu HK, Tsai MJ, Chen YC, Bharath Kumar V, Huang MS, Weng CF. Antiproliferative effect of Toona sinensis leaf extract on non-small-cell lung cancer. Translational Research. 2010, 155:305-314.
Yang HL, Chang WH, Chia YC, Huang CJ, Lu FJ, Hsu HK.and Hseu YC, Toona sinensis extracts induces apoptosis via reactive oxygen species in human premyelocytic leukemia cells. Food and Chemical Toxicology. 2006,44:1978–1988.
Yang YC, Hsu HK, Hwang JH, Hong SJ. Enhancement of glucose uptake in 3T3-L1 adipocytes by Toona sinensis leaf extract. Kaohsiung Journal of Medical Sciences. 2003,19: 327-333.
Yang YC, PH Wang, MC Wei , SI Lue, YR Chen and HK Hsu. 香椿之嗎啡樣鎮痛作用。Health food society of Taiwan. Feb. 70, 2002.
Yeh WC, Cao Z, Classon M, McKnight SL. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes & Development. 1995, 9: 168-181.
Zhou XR, Sun CH, Liu JR, Zhao D. Dietary conjugated linoleic acid increases PPAR gamma gene expression in adipose tissue of obese rat, and improves insulin resistance. Growth Hormone & IGF Research. 2008, 18: 361-368.
Zieleniak A, Wójcik M, Woźniak LA. Structure and physiological functions of the human peroxisome proliferator-activated receptor gamma. Archivum Immunologiae Et therapiae Experimentalis. 2008, 56: 331-345.
行政院衛生署，97年度死因統計表。
肥胖症─原因、病理生理及治療。台北，台灣肥胖醫學會編著，2008。
王珮憓。椿葉水萃取液在Alloxan 所誘發的糖尿病鼠中降血糖作用之研究，高雄醫學大學醫學研究所碩士論文，中華民國九十年六月。
蘇益仁。引藻含PPARs活性劑的生物醫學研究與應用。藻類保健生技研發暨技術交易發表會。2006。
富臣、胡軍、李炎強、盧斌斌。香椿葉CO2 超臨界萃取物的揮發性成分分析研究。中菸菸草化學學組年會暨學術研討會。2004。
楊今詳。抗癌中草藥製劑。渡假出版社有限公司。台北台灣。165 頁。1992。
程劍華、李以鑌。抗癌植物藥及其驗方。江西科學出版社。中國。608 頁。1998。
梁智强。分化流程對脂肪細胞特徵之影響。慈濟大學，分子生物及細胞生物研究所。2005。
劉光凱。肥胖基因的分子研究。慈濟大學，人類遺傳學研究所。2005。
苗明三。實驗動物和實驗動物技術p127-132，中國人民出版社。1997。
賈宜琛。利用高壓異相層析儀分析香椿粗萃取物抗癌成分之研究，中草藥抗癌成分之開發國際研討會，p19, July 27, Kaohsiung, Taiwan. 2007
賈宜琛。香椿抗癌活性成分之研究。繼往開來-台灣之椿，香椿鄉村研發俱樂部。2007。
楊瑞玉。不同分析方法應用於蔬菜抗氧化活性之探討，國立屏東科技大學熱帶農業暨國際合作研究所博士論文，2006。