學術產出-學位論文
文章檢視/開啟
書目匯出
-
題名 水丁香抗老化作用之研究
Studies on the anti-aging effects of Ludwigia octovalvis作者 陳俊伊 貢獻者 王培育
陳俊伊關鍵詞 水丁香
卡路里節制
壽命
氧化壓力
類胰島素生長因子的訊號傳導日期 2011 上傳時間 30-十月-2012 11:28:33 (UTC+8) 摘要 水丁香在台灣已被廣泛用作為香料和中草藥。目前已經被證實擁有許多生物活性，例如抗氧化、抗肝毒性、抗菌及抗癌等。在本研究中，我們利用兩種不同果蠅株w1118和Canton-S(CS)餵食兩種不同的飲食條件，分別為標準食物配方(15% yeast和15% dextrose)及卡路里節制(calorie restriction, CR)食物配方(5% yeast和5% dextrose)，來評估水丁香水萃取物對果蠅老化的影響。我們測試不同水丁香水萃取物濃度(0.1% 及0.5％)的食物對於果蠅的壽命、食物攝取量、下蛋率、活動能力、學習記憶、氧化壓力和基因表現等影響。我們發現水丁香水萃取物在標準食物配方下對於兩種品系的母果蠅均有延長壽命的表現，但並不影響果蠅的下蛋率及活動能力，另外水丁香水萃取物明顯的延緩了老化過程中學習能力退化的情況。然而於CR食物中添加水丁香水萃取物，其延長果蠅壽命的現象則消失，顯示水丁香水萃取物延長果蠅壽命的現象可能透過卡路里節制相關路徑。水丁香水萃取物可增加果蠅抵抗paraquat所引發的氧化壓力，並且降低抗氧化基因如superoxide dismutase(sod1及sod2)、catalase以及果蠅類胰島素胜肽(Drosophila insulin-like peptide, dilp2及dilp3) mRNA的表現。 綜合以上實驗結果我們推測，水丁香水萃取物延長壽命可能的作用機制為：(1)透過卡路里節制的路徑。 (2)影響類胰島素生長因子的訊號傳導(Insulin/IGF-1 signaling)。(3)增加抗氧化壓力的能力。
Ludwigia octovalvis (Jacq.) P. H. Raven has been widely used as a spice and herbal medicine in Taiwan. It has been proved to possess many biological activities, antioxidative, anti-hepatotoxic, anti-bacterial and anticancer properties, for example. In this research, Ludwigia octovalvis extract (LOE) was used in two different diet conditions, one is standard diet (15% yeast and 15% dextrose), and the other is calorie restriction (5% yeast and 5% dextrose). The effect of LOE on the lifespan of the flies was estimated using w1118 and Canton-S strains of Drosophila melanogaster. We also evaluated the effects of 0.1% or 0.5% of LOE on food intake, fecundity, locomotor activity, cognitive performance, anti-oxidative stress and age-related gene expression in flies under standard diet. Our results showed that LOE could extend the lifespan of female flies on both species without affecting the fecundity and locomotor activity. Intriguingly, LOE attenuated the cognitive decline in both male and female flies. The longevity effect of LOE, however, was vanished when the lifespan of the flies was examined under CR diet, suggesting that LOE may extend lifespan through a CR-related pathway. LOE also increased resistance of paraquat-induced oxidative stress and down regulated the mRNA expression of sod1, sod2, cat, dilp2 and dilp3 in the flies. In summary, our results indicated that LOE may extend lifespan through: (1) a CR-related pathway. (2) regulation of Insulin/IGF-1 signaling. (3) increase of anti-oxidative stress.參考文獻 Ahn J, Lee H, Kim S, Park J, Ha T (2008) The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochem Biophys Res Commun 373:545-549. Aitken RJ, Roman SD (2008) Antioxidant systems and oxidative stress in the testes. Adv Exp Med Biol 636:154-171. Anderson RM, Weindruch R (2010) Metabolic reprogramming, caloric restriction and aging. Trends Endocrinol Metab 21:134-141. Arking R, Buck S, Berrios A, Dwyer S, Baker GTIII (1991) Elevated paraquat resistance can be used as a bioassay for longevity in a genetically based long-lived strain of Drosophila. Dev Genet 12:362-370. Arutiunian AV, Kozina LS (2009) Mechanisms of free radical oxidation and its role in aging. Adv Gerontol 22:104-116. Asami DK, McDonald RB, Hagopian K, Horwitz BA, Warman D, Hsiao A, Warden C, Ramsey JJ (2008) Effect of aging, caloric restriction, and uncoupling protein 3 (UCP3) on mitochondrial proton leak in mice. Exp Gerontol 43:1069-1076. Bae JY, Choi JS, Kang SW, Lee YJ, Park J, Kang YH (2010) Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV-B irradiation. Exp Dermatol 19:e182-190. Bai N, He K, Roller M, Zheng B, Chen X, Shao Z, Peng T, Zheng Q (2008) Active compounds from Lagerstroemia speciosa, insulin-like glucose uptake-stimulatory/inhibitory and adipocyte differentiation-inhibitory activities in 3T3-L1 cells. J Agric Food Chem 56:11668-11674. Balamurugan R, Duraipandiyan V, Ignacimuthu S (2011) Antidiabetic activity of gamma-sitosterol isolated from Lippia nodiflora L. in streptozotocin induced diabetic rats. Eur J Pharmacol 667:410-418. Banzouzi JT, Prado R, Menan H, Valentin A, Roumestan C, Mallie M, Pelissier Y, Blache Y (2002) In vitro antiplasmodial activity of extracts of Alchornea cordifolia and identification of an active constituent: ellagic acid. J Ethnopharmacol 81:399-401. Boyd O, Weng P, Sun X, Alberico T, Laslo M, Obenland DM, Kern B, Zou S (2011) Nectarine promotes longevity in Drosophila melanogaster. Free Radic Biol Med 50:1669-1678. Broughton SJ, Piper MD, Ikeya T, Bass TM, Jacobson J, Driege Y, Martinez P, Hafen E, Withers DJ, Leevers SJ, Partridge L (2005) Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci U S A 102:3105-3110. 46 Brown-Borg HM, Borg KE, Meliska CJ, Bartke A (1996) Dwarf mice and the ageing process. Nature 384:33. Burger JM, Buechel SD, Kawecki TJ (2010) Dietary restriction affects lifespan but not cognitive aging in Drosophila melanogaster. Aging Cell 9:327-335. Burkitt MJ, Kadiiska MB, Hanna PM, Jordan SJ, Mason RP (1993) Electron spin resonance spin-trapping investigation into the effects of paraquat and desferrioxamine on hydroxyl radical generation during acute iron poisoning. Mol Pharmacol 43:257-263. Chang CI, Kuo CC, Chang JY, Kuo YH (2004) Three new oleanane-type triterpenes from Ludwigia octovalvis with cytotoxic activity against two human cancer cell lines. J Nat Prod 67:91-93. Chen CP, Lin CC, Namba T (1989) Screening of Taiwanese crude drugs for antibacterial activity against Streptococcus mutans. J Ethnopharmacol 27:285-295. Chiba T, Yamaza H, Shimokawa I (2007) Role of insulin and growth hormone/insulin-like growth factor-I signaling in lifespan extension: rodent longevity models for studying aging and calorie restriction. Curr Genomics 8:423-428. Choi AY, Choi JH, Lee JY, Yoon KS, Choe W, Ha J, Yeo EJ, Kang I (2010) Apigenin protects HT22 murine hippocampal neuronal cells against endoplasmic reticulum stress-induced apoptosis. Neurochem Int 57:143-152. Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, Leevers SJ, Partridge L (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 292:104-106. Ding L, Jin D, Chen X (2010) Luteolin enhances insulin sensitivity via activation of PPARgamma transcriptional activity in adipocytes. J Nutr Biochem 21:941-947. Dorai T, Aggarwal BB (2004) Role of chemopreventive agents in cancer therapy. Cancer Lett 215:129-140. Edderkaoui M, Odinokova I, Ohno I, Gukovsky I, Go VL, Pandol SJ, Gukovskaya AS (2008) Ellagic acid induces apoptosis through inhibition of nuclear factor kappa B in pancreatic cancer cells. World J Gastroenterol 14:3672-3680. Edwards MG, Anderson RM, Yuan M, Kendziorski CM, Weindruch R, Prolla TA (2007) Gene expression profiling of aging reveals activation of a p53-mediated transcriptional program. BMC Genomics 8:80. Elsayed NM (2001) Antioxidant mobilization in response to oxidative stress: a dynamic environmental-nutritional interaction. Nutrition 17:828-834. Fang J, Zhou Q, Shi XL, Jiang BH (2007) Luteolin inhibits insulin-like growth factor 1 47 receptor signaling in prostate cancer cells. Carcinogenesis 28:713-723. Flatt T (2011) Survival costs of reproduction in Drosophila. Exp Gerontol 46:369-375. Fontan-Lozano A, Saez-Cassanelli JL, Inda MC, de los Santos-Arteaga M, Sierra-Dominguez SA, Lopez-Lluch G, Delgado-Garcia JM, Carrion AM (2007) Caloric restriction increases learning consolidation and facilitates synaptic plasticity through mechanisms dependent on NR2B subunits of the NMDA receptor. J Neurosci 27:10185-10195. Fontana L, Partridge L, Longo VD (2010) Extending healthy life span--from yeast to humans. Science 328:321-326. Forshee BA (2006) The aging brain: is function dependent on growth hormone/insulin-like growth factor-1 signaling? Age (Dordr) 28:173-180. Franzen CA, Amargo E, Todorovic V, Desai BV, Huda S, Mirzoeva S, Chiu K, Grzybowski BA, Chew TL, Green KJ, Pelling JC (2009) The chemopreventive bioflavonoid apigenin inhibits prostate cancer cell motility through the focal adhesion kinase/Src signaling mechanism. Cancer Prev Res (Phila) 2:830-841. Galluzzo P, Martini C, Bulzomi P, Leone S, Bolli A, Pallottini V, Marino M (2009) Quercetin-induced apoptotic cascade in cancer cells: antioxidant versus estrogen receptor alpha-dependent mechanisms. Mol Nutr Food Res 53:699-708. Gao H, Wu L, Kuroyanagi M, Harada K, Kawahara N, Nakane T, Umehara K, Hirasawa A, Nakamura Y (2003) Antitumor-promoting constituents from Chaenomeles sinensis KOEHNE and their activities in JB6 mouse epidermal cells. Chem Pharm Bull (Tokyo) 51:1318-1321. Gao L, Laude K, Cai H (2008) Mitochondrial pathophysiology, reactive oxygen species, and cardiovascular diseases. Vet Clin North Am Small Anim Pract 38:137-155, vi. Greeff J, Joubert J, Malan SF, van Dyk S (2011) Antioxidant properties of 4-quinolones and structurally related flavones. Bioorg Med Chem. Ha SK, Lee P, Park JA, Oh HR, Lee SY, Park JH, Lee EH, Ryu JH, Lee KR, Kim SY (2008) Apigenin inhibits the production of NO and PGE2 in microglia and inhibits neuronal cell death in a middle cerebral artery occlusion-induced focal ischemia mice model. Neurochem Int 52:878-886. Han DH, Lee MJ, Kim JH (2006) Antioxidant and apoptosis-inducing activities of ellagic acid. Anticancer Res 26:3601-3606. Haywood AF, Staveley BE (2006) Mutant alpha-synuclein-induced degeneration is reduced by parkin in a fly model of Parkinson`s disease. Genome 49:505-510. He X, Liu RH (2007) Triterpenoids isolated from apple peels have potent 48 antiproliferative activity and may be partially responsible for apple`s anticancer activity. J Agric Food Chem 55:4366-4370. Honda S, Matsuo M (1992) Lifespan shortening of the nematode Caenorhabditis elegans under higher concentrations of oxygen. Mech Ageing Dev 63:235-246. Hsu CL, Yen GC (2006) Induction of cell apoptosis in 3T3-L1 pre-adipocytes by flavonoids is associated with their antioxidant activity. Mol Nutr Food Res 50:1072-1079. Hu D, Cao P, Thiels E, Chu CT, Wu GY, Oury TD, Klann E (2007) Hippocampal long-term potentiation, memory, and longevity in mice that overexpress mitochondrial superoxide dismutase. Neurobiol Learn Mem 87:372-384. Hwang JM, Cho JS, Kim TH, Lee YI (2010) Ellagic acid protects hepatocytes from damage by inhibiting mitochondrial production of reactive oxygen species. Biomed Pharmacother 64:264-270. Hwangbo DS, Gershman B, Tu MP, Palmer M, Tatar M (2004) Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature 429:562-566. Iizuka T, Nagai M, Taniguchi A, Moriyama H, Hoshi K (2007) Inhibitory effects of methyl brevifolincarboxylate isolated from Phyllanthus niruri L. on platelet aggregation. Biol Pharm Bull 30:382-384. Inoue M, Suzuki R, Sakaguchi N, Li Z, Takeda T, Ogihara Y, Jiang BY, Chen Y (1995) Selective induction of cell death in cancer cells by gallic acid. Biol Pharm Bull 18:1526-1530. Ivorra MD, Paya M, Villar A (1990) Effect of beta-sitosterol-3-beta-D-glucoside on insulin secretion in vivo in diabetic rats and in vitro in isolated rat islets of Langerhans. Pharmazie 45:271-273. Jang S, Dilger RN, Johnson RW (2010) Luteolin inhibits microglia and alters hippocampal-dependent spatial working memory in aged mice. J Nutr 140:1892-1898. Jeyabal PV, Syed MB, Venkataraman M, Sambandham JK, Sakthisekaran D (2005) Apigenin inhibits oxidative stress-induced macromolecular damage in N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinogenesis in Wistar albino rats. Mol Carcinog 44:11-20. Jourdain C, Tenca G, Deguercy A, Troplin P, Poelman D (2006) In-vitro effects of polyphenols from cocoa and beta-sitosterol on the growth of human prostate cancer and normal cells. Eur J Cancer Prev 15:353-361. Kampkotter A, Timpel C, Zurawski RF, Ruhl S, Chovolou Y, Proksch P, Watjen W (2008) Increase of stress resistance and lifespan of Caenorhabditis elegans by quercetin. Comp Biochem Physiol B Biochem Mol Biol 149:314-323. 49 Kang KP, Park SK, Kim DH, Sung MJ, Jung YJ, Lee AS, Lee JE, Ramkumar KM, Lee S, Park MH, Roh SG, Kim W (2011) Luteolin ameliorates cisplatin-induced acute kidney injury in mice by regulation of p53-dependent renal tubular apoptosis. Nephrol Dial Transplant 26:814-822. Katic M, Kennedy AR, Leykin I, Norris A, McGettrick A, Gesta S, Russell SJ, Bluher M, Maratos-Flier E, Kahn CR (2007) Mitochondrial gene expression and increased oxidative metabolism: role in increased lifespan of fat-specific insulin receptor knock-out mice. Aging Cell 6:827-839. Kawasaki I, Jeong MH, Oh BK, Shim YH (2010) Apigenin inhibits larval growth of Caenorhabditis elegans through DAF-16 activation. FEBS Lett 584:3587-3591. Kennedy BK, Steffen KK, Kaeberlein M (2007) Ruminations on dietary restriction and aging. Cell Mol Life Sci 64:1323-1328. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366:461-464. Kim DO, Lee KW, Lee HJ, Lee CY (2002) Vitamin C equivalent antioxidant capacity (VCEAC) of phenolic phytochemicals. J Agric Food Chem 50:3713-3717. Kim DW, Choi JH (2000) Effects of age and dietary restriction on animal model SAMP8 mice with learning and memory impairments. J Nutr Health Aging 4:233-238. Kinney BA, Meliska CJ, Steger RW, Bartke A (2001) Evidence that Ames dwarf mice age differently from their normal siblings in behavioral and learning and memory parameters. Horm Behav 39:277-284. Kirkwood TB, Rose MR (1991) Evolution of senescence: late survival sacrificed for reproduction. Philos Trans R Soc Lond B Biol Sci 332:15-24. Komatsu T, Chiba T, Yamaza H, Yamashita K, Shimada A, Hoshiyama Y, Henmi T, Ohtani H, Higami Y, de Cabo R, Ingram DK, Shimokawa I (2008) Manipulation of caloric content but not diet composition, attenuates the deficit in learning and memory of senescence-accelerated mouse strain P8. Exp Gerontol 43:339-346. Kroes BH, van den Berg AJ, Quarles van Ufford HC, van Dijk H, Labadie RP (1992) Anti-inflammatory activity of gallic acid. Planta Med 58:499-504. Le Bourg E (1987) The rate of living theory. Spontaneous locomotor activity, aging and longevity in Drosophila melanogaster. Exp Gerontol 22:359-369. Lee JH, Lee JY, Park JH, Jung HS, Kim JS, Kang SS, Kim YS, Han Y (2007) Immunoregulatory activity by daucosterol, a beta-sitosterol glycoside, induces protective Th1 immune response against disseminated Candidiasis in mice. Vaccine 25:3834-3840. Lee KS, Lee BS, Semnani S, Avanesian A, Um CY, Jeon HJ, Seong KM, Yu K, Min 50 KJ, Jafari M (2010) Curcumin extends life span, improves health span, and modulates the expression of age-associated aging genes in Drosophila melanogaster. Rejuvenation Res 13:561-570. Lin YJ, Seroude L, Benzer S (1998) Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 282:943-946. Linnane AW, Kios M, Vitetta L (2007) Healthy aging: regulation of the metabolome by cellular redox modulation and prooxidant signaling systems: the essential roles of superoxide anion and hydrogen peroxide. Biogerontology 8:445-467. Lithgow GJ, White TM, Melov S, Johnson TE (1995) Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci U S A 92:7540-7544. Liu J, Liu Y, Parkinson A, Klaassen CD (1995) Effect of oleanolic acid on hepatic toxicant-activating and detoxifying systems in mice. J Pharmacol Exp Ther 275:768-774. Liu J, Yu H, Ning X (2006) Effect of quercetin on chronic enhancement of spatial learning and memory of mice. Sci China C Life Sci 49:583-590. Liu R, Liu IY, Bi X, Thompson RF, Doctrow SR, Malfroy B, Baudry M (2003) Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase/catalase mimetics. Proc Natl Acad Sci U S A 100:8526-8531. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402-408. Longo VD, Finch CE (2003) Evolutionary medicine: from dwarf model systems to healthy centenarians? Science 299:1342-1346. Lucio KA, Rocha Gda G, Moncao-Ribeiro LC, Fernandes J, Takiya CM, Gattass CR (2011) Oleanolic Acid Initiates Apoptosis in Non-Small Cell Lung Cancer Cell Lines and Reduces Metastasis of a B16F10 Melanoma Model In Vivo. PLoS One 6:e28596. Magwere T, West M, Riyahi K, Murphy MP, Smith RA, Partridge L (2006) The effects of exogenous antioxidants on lifespan and oxidative stress resistance in Drosophila melanogaster. Mech Ageing Dev 127:356-370. Mair W, Dillin A (2008) Aging and survival: the genetics of life span extension by dietary restriction. Annu Rev Biochem 77:727-754. Martin GM, Austad SN, Johnson TE (1996) Genetic analysis of ageing: role of oxidative damage and environmental stresses. Nat Genet 13:25-34. Masoro EJ (2000) Caloric restriction and aging: an update. Exp Gerontol 35:299-305. Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F, 51 Hwang PM (2006) p53 regulates mitochondrial respiration. Science 312:1650-1653. McCay CM, Crowell MF, Maynard LA (1989) The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition 5:155-171; discussion 172. Mengoni F, Lichtner M, Battinelli L, Marzi M, Mastroianni CM, Vullo V, Mazzanti G (2002) In vitro anti-HIV activity of oleanolic acid on infected human mononuclear cells. Planta Med 68:111-114. Mery F, Kawecki TJ (2005) A cost of long-term memory in Drosophila. Science 308:1148. Murakami C, Ishijima K, Hirota M, Sakaguchi K, Yoshida H, Mizushina Y (2002) Novel anti-inflammatory compounds from Rubus sieboldii, triterpenoids, are inhibitors of mammalian DNA polymerases. Biochim Biophys Acta 1596:193-200. Novoseltsev VN, Novoseltseva JA, Boyko SI, Yashin AI (2003) What fecundity patterns indicate about aging and longevity: insights from Drosophila studies. J Gerontol A Biol Sci Med Sci 58:484-494. Orr WC, Sohal RS (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263:1128-1130. Parkes TL, Elia AJ, Dickinson D, Hilliker AJ, Phillips JP, Boulianne GL (1998) Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat Genet 19:171-174. Peng C, Chan HY, Li YM, Huang Y, Chen ZY (2009) Black tea theaflavins extend the lifespan of fruit flies. Exp Gerontol 44:773-783. Piper MD, Bartke A (2008) Diet and aging. Cell Metab 8:99-104. Punithavathi VR, Prince PS, Kumar R, Selvakumari J (2011) Antihyperglycaemic, antilipid peroxidative and antioxidant effects of gallic acid on streptozotocin induced diabetic Wistar rats. Eur J Pharmacol 650:465-471. Qiu X, Brown K, Hirschey MD, Verdin E, Chen D (2010) Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab 12:662-667. Reisman SA, Aleksunes LM, Klaassen CD (2009) Oleanolic acid activates Nrf2 and protects from acetaminophen hepatotoxicity via Nrf2-dependent and Nrf2-independent processes. Biochem Pharmacol 77:1273-1282. Rhodenizer D, Martin I, Bhandari P, Pletcher SD, Grotewiel M (2008) Genetic and environmental factors impact age-related impairment of negative geotaxis in Drosophila by altering age-dependent climbing speed. Exp Gerontol 43:739-748. Ristow M, Schmeisser S (2011) Extending life span by increasing oxidative stress. Free Radic Biol Med 51:327-336. 52 Rosato E, Kyriacou CP (2006) Analysis of locomotor activity rhythms in Drosophila. Nat Protoc 1:559-568. Rosenzweig ES, Barnes CA (2003) Impact of aging on hippocampal function: plasticity, network dynamics, and cognition. Prog Neurobiol 69:143-179. Saaby L, Jager AK, Moesby L, Hansen EW, Christensen SB (2011) Isolation of immunomodulatory triterpene acids from a standardized rose hip powder (Rosa canina L.). Phytother Res 25:195-201. Sampayo JN, Gill MS, Lithgow GJ (2003) Oxidative stress and aging--the use of superoxide dismutase/catalase mimetics to extend lifespan. Biochem Soc Trans 31:1305-1307. Seelinger G, Merfort I, Schempp CM (2008) Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta Med 74:1667-1677. Senthilkumar K, Elumalai P, Arunkumar R, Banudevi S, Gunadharini ND, Sharmila G, Selvakumar K, Arunakaran J (2010) Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3). Mol Cell Biochem 344:173-184. Shukla S, Maclennan GT, Fu P, Gupta S (2011) Apigenin Attenuates Insulin-Like Growth Factor-I Signaling in an Autochthonous Mouse Prostate Cancer Model. Pharm Res. Simon AF, Liang DT, Krantz DE (2006) Differential decline in behavioral performance of Drosophila melanogaster with age. Mech Ageing Dev 127:647-651. Singh JP, Selvendiran K, Banu SM, Padmavathi R, Sakthisekaran D (2004) Protective role of Apigenin on the status of lipid peroxidation and antioxidant defense against hepatocarcinogenesis in Wistar albino rats. Phytomedicine 11:309-314. Sohal RS, Weindruch R (1996) Oxidative stress, caloric restriction, and aging. Science 273:59-63. Strobel P, Allard C, Perez-Acle T, Calderon R, Aldunate R, Leighton F (2005) Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. Biochem J 386:471-478. Sztanke K, Pasternak K (2003) The Maillard reaction inhibitors and their biological and therapeutic significance. Ann Univ Mariae Curie Sklodowska Med 58:156-158. Thompson KH, Lichter J, LeBel C, Scaife MC, McNeill JH, Orvig C (2009) Vanadium treatment of type 2 diabetes: a view to the future. J Inorg Biochem 103:554-558. Tsai CH, Lo SK, See LC, Chen HZ, Chen RS, Weng YH, Chang FC, Lu CS (2002) 53 Environmental risk factors of young onset Parkinson`s disease: a case-control study. Clin Neurol Neurosurg 104:328-333. Upadhyay K, Gupta NK, Dixit VK (2011) Development and characterization of phyto-vesicles of beta-sitosterol for the treatment of androgenetic alopecia. Arch Dermatol Res. Wang PY, Neretti N, Whitaker R, Hosier S, Chang C, Lu D, Rogina B, Helfand SL (2009) Long-lived Indy and calorie restriction interact to extend life span. Proc Natl Acad Sci U S A 106:9262-9267. Wei H, Tye L, Bresnick E, Birt DF (1990) Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice. Cancer Res 50:499-502. Wei YH, Lu CY, Wei CY, Ma YS, Lee HC (2001) Oxidative stress in human aging and mitochondrial disease-consequences of defective mitochondrial respiration and impaired antioxidant enzyme system. Chin J Physiol 44:1-11. Wilson MA, Shukitt-Hale B, Kalt W, Ingram DK, Joseph JA, Wolkow CA (2006) Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging Cell 5:59-68. Wu SJ, Ng LT, Wang GH, Huang YJ, Chen JL, Sun FM (2010) Chlorophyll a, an active anti-proliferative compound of Ludwigia octovalvis, activates the CD95 (APO-1/CD95) system and AMPK pathway in 3T3-L1 cells. Food Chem Toxicol 48:716-721. Xia S, Miyashita T, Fu TF, Lin WY, Wu CL, Pyzocha L, Lin IR, Saitoe M, Tully T, Chiang AS (2005) NMDA receptors mediate olfactory learning and memory in Drosophila. Curr Biol 15:603-615. Xu B, Li XX, He GR, Hu JJ, Mu X, Tian S, Du GH (2010) Luteolin promotes long-term potentiation and improves cognitive functions in chronic cerebral hypoperfused rats. Eur J Pharmacol 627:99-105. Yamazaki D, Horiuchi J, Nakagami Y, Nagano S, Tamura T, Saitoe M (2007) The Drosophila DCO mutation suppresses age-related memory impairment without affecting lifespan. Nat Neurosci 10:478-484. Yan J, Yang XW (2005) [Studies on the chemical constituents in herb of Ludwigia octovalvis]. Zhongguo Zhong Yao Za Zhi 30:1923-1926. Yang LL, Yen KY, Kiso Y, Hikino H (1987) Antihepatotoxic actions of Formosan plant drugs. J Ethnopharmacol 19:103-110. Young JM, Wessnitzer J, Armstrong JD, Webb B (2011) Elemental and non-elemental olfactory learning in Drosophila. Neurobiol Learn Mem 96:339-352. Zelko IN, Mariani TJ, Folz RJ (2002) Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) 54 gene structures, evolution, and expression. Free Radic Biol Med 33:337-349. Zhang Q, Chang Z, Wang Q (2006) Ursane triterpenoids inhibit atherosclerosis and xanthoma in LDL receptor knockout mice. Cardiovasc Drugs Ther 20:349-357. Zhao Y, Yang G, Ren D, Zhang X, Yin Q, Sun X (2011) Luteolin suppresses growth and migration of human lung cancer cells. Mol Biol Rep 38:1115-1119. Zhong Y, Zuo C, Li F, Ding X, Yao Q, Wu K, Zhang Q, Wang Z, Zhou LW, Lan J, Wang X (1998) [Chemical constituents of Phyllanthus urinaria L. and its antiviral activity against hepatitis B virus]. Zhongguo Zhong Yao Za Zhi 23:363-364, 384. 描述 碩士
國立政治大學
神經科學研究所
98754007
100資料來源 http://thesis.lib.nccu.edu.tw/record/#G0098754007 資料類型 thesis dc.contributor.advisor 王培育 zh_TW dc.contributor.author (作者) 陳俊伊 zh_TW dc.creator (作者) 陳俊伊 zh_TW dc.date (日期) 2011 en_US dc.date.accessioned 30-十月-2012 11:28:33 (UTC+8) - dc.date.available 30-十月-2012 11:28:33 (UTC+8) - dc.date.issued (上傳時間) 30-十月-2012 11:28:33 (UTC+8) - dc.identifier (其他 識別碼) G0098754007 en_US dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/54654 - dc.description (描述) 碩士 zh_TW dc.description (描述) 國立政治大學 zh_TW dc.description (描述) 神經科學研究所 zh_TW dc.description (描述) 98754007 zh_TW dc.description (描述) 100 zh_TW dc.description.abstract (摘要) 水丁香在台灣已被廣泛用作為香料和中草藥。目前已經被證實擁有許多生物活性，例如抗氧化、抗肝毒性、抗菌及抗癌等。在本研究中，我們利用兩種不同果蠅株w1118和Canton-S(CS)餵食兩種不同的飲食條件，分別為標準食物配方(15% yeast和15% dextrose)及卡路里節制(calorie restriction, CR)食物配方(5% yeast和5% dextrose)，來評估水丁香水萃取物對果蠅老化的影響。我們測試不同水丁香水萃取物濃度(0.1% 及0.5％)的食物對於果蠅的壽命、食物攝取量、下蛋率、活動能力、學習記憶、氧化壓力和基因表現等影響。我們發現水丁香水萃取物在標準食物配方下對於兩種品系的母果蠅均有延長壽命的表現，但並不影響果蠅的下蛋率及活動能力，另外水丁香水萃取物明顯的延緩了老化過程中學習能力退化的情況。然而於CR食物中添加水丁香水萃取物，其延長果蠅壽命的現象則消失，顯示水丁香水萃取物延長果蠅壽命的現象可能透過卡路里節制相關路徑。水丁香水萃取物可增加果蠅抵抗paraquat所引發的氧化壓力，並且降低抗氧化基因如superoxide dismutase(sod1及sod2)、catalase以及果蠅類胰島素胜肽(Drosophila insulin-like peptide, dilp2及dilp3) mRNA的表現。 綜合以上實驗結果我們推測，水丁香水萃取物延長壽命可能的作用機制為：(1)透過卡路里節制的路徑。 (2)影響類胰島素生長因子的訊號傳導(Insulin/IGF-1 signaling)。(3)增加抗氧化壓力的能力。 zh_TW dc.description.abstract (摘要) Ludwigia octovalvis (Jacq.) P. H. Raven has been widely used as a spice and herbal medicine in Taiwan. It has been proved to possess many biological activities, antioxidative, anti-hepatotoxic, anti-bacterial and anticancer properties, for example. In this research, Ludwigia octovalvis extract (LOE) was used in two different diet conditions, one is standard diet (15% yeast and 15% dextrose), and the other is calorie restriction (5% yeast and 5% dextrose). The effect of LOE on the lifespan of the flies was estimated using w1118 and Canton-S strains of Drosophila melanogaster. We also evaluated the effects of 0.1% or 0.5% of LOE on food intake, fecundity, locomotor activity, cognitive performance, anti-oxidative stress and age-related gene expression in flies under standard diet. Our results showed that LOE could extend the lifespan of female flies on both species without affecting the fecundity and locomotor activity. Intriguingly, LOE attenuated the cognitive decline in both male and female flies. The longevity effect of LOE, however, was vanished when the lifespan of the flies was examined under CR diet, suggesting that LOE may extend lifespan through a CR-related pathway. LOE also increased resistance of paraquat-induced oxidative stress and down regulated the mRNA expression of sod1, sod2, cat, dilp2 and dilp3 in the flies. In summary, our results indicated that LOE may extend lifespan through: (1) a CR-related pathway. (2) regulation of Insulin/IGF-1 signaling. (3) increase of anti-oxidative stress. en_US dc.description.tableofcontents 中文摘要.............................................. I 英文摘要.............................................. II 目錄 .................................................III 圖次 ..................................................VI 表次 ................................................ VII 縮寫對照表 ........................................... VIII 中英文名詞對照表 ...................................... IX 第一章 緒論 .......................................... 01 第一節、 水丁香簡介 ................................... 01 第二節、 老化的理論 ................................... 02 一、 卡路里節制(CR)與老化關聯 .......................... 03 二、 氧化壓力(oxidative stress)與老化關聯 .............. 04 三、 基因與壽命的相關性 ................................ 05 (一) 抗氧化酵素(antioxidant enzymes) .................. 05 (二) 類胰島素生長因子的訊號傳導(insulin/IGF-1 signaling) 06 第三節、 老化相關指標 ................................... 06 一、 生殖能力(fecundity) ............................... 06 二、 自發性活動能力(spontaneous motor activity) ......... 07 三、 老化的記憶損害AMI（age-related memory impairment） ...07 第四節、 利用果蠅模式之藥物篩選研究的優處 .................. 08 第五節、 實驗設計 ....................................... 08 第二章 實驗材料與研究方法 ................................ 09 第一節、 實驗材料 ....................................... 09 一、 實驗藥品 ........................................... 09 二、 果蠅種類 ........................................... 10 三、 食物培養基配方 ...................................... 10 第二節、 研究方法 ........................................ 10 一、 水丁香水抽出物之製備 ................................. 10 二、 果蠅飼養與存活率分析試驗 ...............................11 三、抗氧化壓力試驗(paraquat) .............................. 11 四、 食物攝取量試驗 ....................................... 11 五、 生殖能力試驗 ......................................... 12 六、 自發性活動能力試驗 .................................... 12 七、 學習能力試驗 ......................................... 12 八、 mRNA之定量分析 ....................................... 13 (一) RNA之萃取 ........................................... 13 (二) DNase treatment .................................... 14 (三) First strand cDNA synthesis ........................ 14 (四) 即時定量聚合酶連鎖反應(quantitative PCR)............... 15 九、 統計分析 ............................................ 16 第三章 結果 .............................................. 17 第一節、 餵食水丁香水萃取物對於w1118果蠅壽命的影響 ........... 17 第二節、 餵食水丁香水萃取物對於CS果蠅壽命的影響 .............. 20 第三節、 餵食水丁香水萃取物對於w1118果蠅食物攝取量的分析 ...... 23 第四節、 餵食水丁香水萃取物對於w1118果蠅下蛋率的影響 ......... 25 第五節、 餵食水丁香水萃取物對於w1118果蠅自發性活動能力的影響 .. 27 第六節、 餵食水丁香水萃取物對於w1118果蠅學習能力的影響 ....... 29 第七節、 在CR狀態餵食水丁香水萃取物對於w1118果蠅壽命的影響 ... 31 第八節、 餵食水丁香水萃取物對於w1118果蠅抗氧化能力試驗分析 ... 34 第九節、 餵食水丁香水萃取物對於w1118果蠅Insulin/IGF-1 signaling及抗氧化基因表現的分析 .................................... 37 第四章 討論 .............................................. 39 第五章 結論 .............................................. 44 參考文獻 ................................................. 45 附錄圖一、水丁香全株之外觀 ................................. XI 附錄圖二、抗氧化防禦系統示意圖 ............................ XII 附錄圖三、酵母菌至哺乳類動物，insulin/IGF-1 signaling與壽命之間訊息調控模式 . ............................................XIII 附錄圖四、實驗流程圖 ..................................... XIV 附錄圖五、水丁香水萃示意流程圖 ............................ XV 附錄圖六、果蠅活動能力偵測儀器 ............................. V 附錄圖七、t-maze儀器 ................................... XVII 附錄表一、水丁香所含七大分類與十三種化合物個別之生物活性表 .. XVIII zh_TW dc.language.iso en_US - dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G0098754007 en_US dc.subject (關鍵詞) 水丁香 zh_TW dc.subject (關鍵詞) 卡路里節制 zh_TW dc.subject (關鍵詞) 壽命 zh_TW dc.subject (關鍵詞) 氧化壓力 zh_TW dc.subject (關鍵詞) 類胰島素生長因子的訊號傳導 zh_TW dc.title (題名) 水丁香抗老化作用之研究 zh_TW dc.title (題名) Studies on the anti-aging effects of Ludwigia octovalvis en_US dc.type (資料類型) thesis en dc.relation.reference (參考文獻) Ahn J, Lee H, Kim S, Park J, Ha T (2008) The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochem Biophys Res Commun 373:545-549. Aitken RJ, Roman SD (2008) Antioxidant systems and oxidative stress in the testes. Adv Exp Med Biol 636:154-171. Anderson RM, Weindruch R (2010) Metabolic reprogramming, caloric restriction and aging. Trends Endocrinol Metab 21:134-141. Arking R, Buck S, Berrios A, Dwyer S, Baker GTIII (1991) Elevated paraquat resistance can be used as a bioassay for longevity in a genetically based long-lived strain of Drosophila. Dev Genet 12:362-370. Arutiunian AV, Kozina LS (2009) Mechanisms of free radical oxidation and its role in aging. Adv Gerontol 22:104-116. Asami DK, McDonald RB, Hagopian K, Horwitz BA, Warman D, Hsiao A, Warden C, Ramsey JJ (2008) Effect of aging, caloric restriction, and uncoupling protein 3 (UCP3) on mitochondrial proton leak in mice. Exp Gerontol 43:1069-1076. Bae JY, Choi JS, Kang SW, Lee YJ, Park J, Kang YH (2010) Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV-B irradiation. Exp Dermatol 19:e182-190. Bai N, He K, Roller M, Zheng B, Chen X, Shao Z, Peng T, Zheng Q (2008) Active compounds from Lagerstroemia speciosa, insulin-like glucose uptake-stimulatory/inhibitory and adipocyte differentiation-inhibitory activities in 3T3-L1 cells. J Agric Food Chem 56:11668-11674. Balamurugan R, Duraipandiyan V, Ignacimuthu S (2011) Antidiabetic activity of gamma-sitosterol isolated from Lippia nodiflora L. in streptozotocin induced diabetic rats. Eur J Pharmacol 667:410-418. Banzouzi JT, Prado R, Menan H, Valentin A, Roumestan C, Mallie M, Pelissier Y, Blache Y (2002) In vitro antiplasmodial activity of extracts of Alchornea cordifolia and identification of an active constituent: ellagic acid. J Ethnopharmacol 81:399-401. Boyd O, Weng P, Sun X, Alberico T, Laslo M, Obenland DM, Kern B, Zou S (2011) Nectarine promotes longevity in Drosophila melanogaster. Free Radic Biol Med 50:1669-1678. Broughton SJ, Piper MD, Ikeya T, Bass TM, Jacobson J, Driege Y, Martinez P, Hafen E, Withers DJ, Leevers SJ, Partridge L (2005) Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci U S A 102:3105-3110. 46 Brown-Borg HM, Borg KE, Meliska CJ, Bartke A (1996) Dwarf mice and the ageing process. Nature 384:33. Burger JM, Buechel SD, Kawecki TJ (2010) Dietary restriction affects lifespan but not cognitive aging in Drosophila melanogaster. Aging Cell 9:327-335. Burkitt MJ, Kadiiska MB, Hanna PM, Jordan SJ, Mason RP (1993) Electron spin resonance spin-trapping investigation into the effects of paraquat and desferrioxamine on hydroxyl radical generation during acute iron poisoning. Mol Pharmacol 43:257-263. Chang CI, Kuo CC, Chang JY, Kuo YH (2004) Three new oleanane-type triterpenes from Ludwigia octovalvis with cytotoxic activity against two human cancer cell lines. J Nat Prod 67:91-93. Chen CP, Lin CC, Namba T (1989) Screening of Taiwanese crude drugs for antibacterial activity against Streptococcus mutans. J Ethnopharmacol 27:285-295. Chiba T, Yamaza H, Shimokawa I (2007) Role of insulin and growth hormone/insulin-like growth factor-I signaling in lifespan extension: rodent longevity models for studying aging and calorie restriction. Curr Genomics 8:423-428. Choi AY, Choi JH, Lee JY, Yoon KS, Choe W, Ha J, Yeo EJ, Kang I (2010) Apigenin protects HT22 murine hippocampal neuronal cells against endoplasmic reticulum stress-induced apoptosis. Neurochem Int 57:143-152. Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, Leevers SJ, Partridge L (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 292:104-106. Ding L, Jin D, Chen X (2010) Luteolin enhances insulin sensitivity via activation of PPARgamma transcriptional activity in adipocytes. J Nutr Biochem 21:941-947. Dorai T, Aggarwal BB (2004) Role of chemopreventive agents in cancer therapy. Cancer Lett 215:129-140. Edderkaoui M, Odinokova I, Ohno I, Gukovsky I, Go VL, Pandol SJ, Gukovskaya AS (2008) Ellagic acid induces apoptosis through inhibition of nuclear factor kappa B in pancreatic cancer cells. World J Gastroenterol 14:3672-3680. Edwards MG, Anderson RM, Yuan M, Kendziorski CM, Weindruch R, Prolla TA (2007) Gene expression profiling of aging reveals activation of a p53-mediated transcriptional program. BMC Genomics 8:80. Elsayed NM (2001) Antioxidant mobilization in response to oxidative stress: a dynamic environmental-nutritional interaction. Nutrition 17:828-834. Fang J, Zhou Q, Shi XL, Jiang BH (2007) Luteolin inhibits insulin-like growth factor 1 47 receptor signaling in prostate cancer cells. Carcinogenesis 28:713-723. Flatt T (2011) Survival costs of reproduction in Drosophila. Exp Gerontol 46:369-375. Fontan-Lozano A, Saez-Cassanelli JL, Inda MC, de los Santos-Arteaga M, Sierra-Dominguez SA, Lopez-Lluch G, Delgado-Garcia JM, Carrion AM (2007) Caloric restriction increases learning consolidation and facilitates synaptic plasticity through mechanisms dependent on NR2B subunits of the NMDA receptor. J Neurosci 27:10185-10195. Fontana L, Partridge L, Longo VD (2010) Extending healthy life span--from yeast to humans. Science 328:321-326. Forshee BA (2006) The aging brain: is function dependent on growth hormone/insulin-like growth factor-1 signaling? Age (Dordr) 28:173-180. Franzen CA, Amargo E, Todorovic V, Desai BV, Huda S, Mirzoeva S, Chiu K, Grzybowski BA, Chew TL, Green KJ, Pelling JC (2009) The chemopreventive bioflavonoid apigenin inhibits prostate cancer cell motility through the focal adhesion kinase/Src signaling mechanism. Cancer Prev Res (Phila) 2:830-841. Galluzzo P, Martini C, Bulzomi P, Leone S, Bolli A, Pallottini V, Marino M (2009) Quercetin-induced apoptotic cascade in cancer cells: antioxidant versus estrogen receptor alpha-dependent mechanisms. Mol Nutr Food Res 53:699-708. Gao H, Wu L, Kuroyanagi M, Harada K, Kawahara N, Nakane T, Umehara K, Hirasawa A, Nakamura Y (2003) Antitumor-promoting constituents from Chaenomeles sinensis KOEHNE and their activities in JB6 mouse epidermal cells. Chem Pharm Bull (Tokyo) 51:1318-1321. Gao L, Laude K, Cai H (2008) Mitochondrial pathophysiology, reactive oxygen species, and cardiovascular diseases. Vet Clin North Am Small Anim Pract 38:137-155, vi. Greeff J, Joubert J, Malan SF, van Dyk S (2011) Antioxidant properties of 4-quinolones and structurally related flavones. Bioorg Med Chem. Ha SK, Lee P, Park JA, Oh HR, Lee SY, Park JH, Lee EH, Ryu JH, Lee KR, Kim SY (2008) Apigenin inhibits the production of NO and PGE2 in microglia and inhibits neuronal cell death in a middle cerebral artery occlusion-induced focal ischemia mice model. Neurochem Int 52:878-886. Han DH, Lee MJ, Kim JH (2006) Antioxidant and apoptosis-inducing activities of ellagic acid. Anticancer Res 26:3601-3606. Haywood AF, Staveley BE (2006) Mutant alpha-synuclein-induced degeneration is reduced by parkin in a fly model of Parkinson`s disease. Genome 49:505-510. He X, Liu RH (2007) Triterpenoids isolated from apple peels have potent 48 antiproliferative activity and may be partially responsible for apple`s anticancer activity. J Agric Food Chem 55:4366-4370. Honda S, Matsuo M (1992) Lifespan shortening of the nematode Caenorhabditis elegans under higher concentrations of oxygen. Mech Ageing Dev 63:235-246. Hsu CL, Yen GC (2006) Induction of cell apoptosis in 3T3-L1 pre-adipocytes by flavonoids is associated with their antioxidant activity. Mol Nutr Food Res 50:1072-1079. Hu D, Cao P, Thiels E, Chu CT, Wu GY, Oury TD, Klann E (2007) Hippocampal long-term potentiation, memory, and longevity in mice that overexpress mitochondrial superoxide dismutase. Neurobiol Learn Mem 87:372-384. Hwang JM, Cho JS, Kim TH, Lee YI (2010) Ellagic acid protects hepatocytes from damage by inhibiting mitochondrial production of reactive oxygen species. Biomed Pharmacother 64:264-270. Hwangbo DS, Gershman B, Tu MP, Palmer M, Tatar M (2004) Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature 429:562-566. Iizuka T, Nagai M, Taniguchi A, Moriyama H, Hoshi K (2007) Inhibitory effects of methyl brevifolincarboxylate isolated from Phyllanthus niruri L. on platelet aggregation. Biol Pharm Bull 30:382-384. Inoue M, Suzuki R, Sakaguchi N, Li Z, Takeda T, Ogihara Y, Jiang BY, Chen Y (1995) Selective induction of cell death in cancer cells by gallic acid. Biol Pharm Bull 18:1526-1530. Ivorra MD, Paya M, Villar A (1990) Effect of beta-sitosterol-3-beta-D-glucoside on insulin secretion in vivo in diabetic rats and in vitro in isolated rat islets of Langerhans. Pharmazie 45:271-273. Jang S, Dilger RN, Johnson RW (2010) Luteolin inhibits microglia and alters hippocampal-dependent spatial working memory in aged mice. J Nutr 140:1892-1898. Jeyabal PV, Syed MB, Venkataraman M, Sambandham JK, Sakthisekaran D (2005) Apigenin inhibits oxidative stress-induced macromolecular damage in N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinogenesis in Wistar albino rats. Mol Carcinog 44:11-20. Jourdain C, Tenca G, Deguercy A, Troplin P, Poelman D (2006) In-vitro effects of polyphenols from cocoa and beta-sitosterol on the growth of human prostate cancer and normal cells. Eur J Cancer Prev 15:353-361. Kampkotter A, Timpel C, Zurawski RF, Ruhl S, Chovolou Y, Proksch P, Watjen W (2008) Increase of stress resistance and lifespan of Caenorhabditis elegans by quercetin. Comp Biochem Physiol B Biochem Mol Biol 149:314-323. 49 Kang KP, Park SK, Kim DH, Sung MJ, Jung YJ, Lee AS, Lee JE, Ramkumar KM, Lee S, Park MH, Roh SG, Kim W (2011) Luteolin ameliorates cisplatin-induced acute kidney injury in mice by regulation of p53-dependent renal tubular apoptosis. Nephrol Dial Transplant 26:814-822. Katic M, Kennedy AR, Leykin I, Norris A, McGettrick A, Gesta S, Russell SJ, Bluher M, Maratos-Flier E, Kahn CR (2007) Mitochondrial gene expression and increased oxidative metabolism: role in increased lifespan of fat-specific insulin receptor knock-out mice. Aging Cell 6:827-839. Kawasaki I, Jeong MH, Oh BK, Shim YH (2010) Apigenin inhibits larval growth of Caenorhabditis elegans through DAF-16 activation. FEBS Lett 584:3587-3591. Kennedy BK, Steffen KK, Kaeberlein M (2007) Ruminations on dietary restriction and aging. Cell Mol Life Sci 64:1323-1328. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366:461-464. Kim DO, Lee KW, Lee HJ, Lee CY (2002) Vitamin C equivalent antioxidant capacity (VCEAC) of phenolic phytochemicals. J Agric Food Chem 50:3713-3717. Kim DW, Choi JH (2000) Effects of age and dietary restriction on animal model SAMP8 mice with learning and memory impairments. J Nutr Health Aging 4:233-238. Kinney BA, Meliska CJ, Steger RW, Bartke A (2001) Evidence that Ames dwarf mice age differently from their normal siblings in behavioral and learning and memory parameters. Horm Behav 39:277-284. Kirkwood TB, Rose MR (1991) Evolution of senescence: late survival sacrificed for reproduction. Philos Trans R Soc Lond B Biol Sci 332:15-24. Komatsu T, Chiba T, Yamaza H, Yamashita K, Shimada A, Hoshiyama Y, Henmi T, Ohtani H, Higami Y, de Cabo R, Ingram DK, Shimokawa I (2008) Manipulation of caloric content but not diet composition, attenuates the deficit in learning and memory of senescence-accelerated mouse strain P8. Exp Gerontol 43:339-346. Kroes BH, van den Berg AJ, Quarles van Ufford HC, van Dijk H, Labadie RP (1992) Anti-inflammatory activity of gallic acid. Planta Med 58:499-504. Le Bourg E (1987) The rate of living theory. Spontaneous locomotor activity, aging and longevity in Drosophila melanogaster. Exp Gerontol 22:359-369. Lee JH, Lee JY, Park JH, Jung HS, Kim JS, Kang SS, Kim YS, Han Y (2007) Immunoregulatory activity by daucosterol, a beta-sitosterol glycoside, induces protective Th1 immune response against disseminated Candidiasis in mice. Vaccine 25:3834-3840. Lee KS, Lee BS, Semnani S, Avanesian A, Um CY, Jeon HJ, Seong KM, Yu K, Min 50 KJ, Jafari M (2010) Curcumin extends life span, improves health span, and modulates the expression of age-associated aging genes in Drosophila melanogaster. Rejuvenation Res 13:561-570. Lin YJ, Seroude L, Benzer S (1998) Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 282:943-946. Linnane AW, Kios M, Vitetta L (2007) Healthy aging: regulation of the metabolome by cellular redox modulation and prooxidant signaling systems: the essential roles of superoxide anion and hydrogen peroxide. Biogerontology 8:445-467. Lithgow GJ, White TM, Melov S, Johnson TE (1995) Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci U S A 92:7540-7544. Liu J, Liu Y, Parkinson A, Klaassen CD (1995) Effect of oleanolic acid on hepatic toxicant-activating and detoxifying systems in mice. J Pharmacol Exp Ther 275:768-774. Liu J, Yu H, Ning X (2006) Effect of quercetin on chronic enhancement of spatial learning and memory of mice. Sci China C Life Sci 49:583-590. Liu R, Liu IY, Bi X, Thompson RF, Doctrow SR, Malfroy B, Baudry M (2003) Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase/catalase mimetics. Proc Natl Acad Sci U S A 100:8526-8531. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402-408. Longo VD, Finch CE (2003) Evolutionary medicine: from dwarf model systems to healthy centenarians? Science 299:1342-1346. Lucio KA, Rocha Gda G, Moncao-Ribeiro LC, Fernandes J, Takiya CM, Gattass CR (2011) Oleanolic Acid Initiates Apoptosis in Non-Small Cell Lung Cancer Cell Lines and Reduces Metastasis of a B16F10 Melanoma Model In Vivo. PLoS One 6:e28596. Magwere T, West M, Riyahi K, Murphy MP, Smith RA, Partridge L (2006) The effects of exogenous antioxidants on lifespan and oxidative stress resistance in Drosophila melanogaster. Mech Ageing Dev 127:356-370. Mair W, Dillin A (2008) Aging and survival: the genetics of life span extension by dietary restriction. Annu Rev Biochem 77:727-754. Martin GM, Austad SN, Johnson TE (1996) Genetic analysis of ageing: role of oxidative damage and environmental stresses. Nat Genet 13:25-34. Masoro EJ (2000) Caloric restriction and aging: an update. Exp Gerontol 35:299-305. Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F, 51 Hwang PM (2006) p53 regulates mitochondrial respiration. Science 312:1650-1653. McCay CM, Crowell MF, Maynard LA (1989) The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition 5:155-171; discussion 172. Mengoni F, Lichtner M, Battinelli L, Marzi M, Mastroianni CM, Vullo V, Mazzanti G (2002) In vitro anti-HIV activity of oleanolic acid on infected human mononuclear cells. Planta Med 68:111-114. Mery F, Kawecki TJ (2005) A cost of long-term memory in Drosophila. Science 308:1148. Murakami C, Ishijima K, Hirota M, Sakaguchi K, Yoshida H, Mizushina Y (2002) Novel anti-inflammatory compounds from Rubus sieboldii, triterpenoids, are inhibitors of mammalian DNA polymerases. Biochim Biophys Acta 1596:193-200. Novoseltsev VN, Novoseltseva JA, Boyko SI, Yashin AI (2003) What fecundity patterns indicate about aging and longevity: insights from Drosophila studies. J Gerontol A Biol Sci Med Sci 58:484-494. Orr WC, Sohal RS (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263:1128-1130. Parkes TL, Elia AJ, Dickinson D, Hilliker AJ, Phillips JP, Boulianne GL (1998) Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat Genet 19:171-174. Peng C, Chan HY, Li YM, Huang Y, Chen ZY (2009) Black tea theaflavins extend the lifespan of fruit flies. Exp Gerontol 44:773-783. Piper MD, Bartke A (2008) Diet and aging. Cell Metab 8:99-104. Punithavathi VR, Prince PS, Kumar R, Selvakumari J (2011) Antihyperglycaemic, antilipid peroxidative and antioxidant effects of gallic acid on streptozotocin induced diabetic Wistar rats. Eur J Pharmacol 650:465-471. Qiu X, Brown K, Hirschey MD, Verdin E, Chen D (2010) Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab 12:662-667. Reisman SA, Aleksunes LM, Klaassen CD (2009) Oleanolic acid activates Nrf2 and protects from acetaminophen hepatotoxicity via Nrf2-dependent and Nrf2-independent processes. Biochem Pharmacol 77:1273-1282. Rhodenizer D, Martin I, Bhandari P, Pletcher SD, Grotewiel M (2008) Genetic and environmental factors impact age-related impairment of negative geotaxis in Drosophila by altering age-dependent climbing speed. Exp Gerontol 43:739-748. Ristow M, Schmeisser S (2011) Extending life span by increasing oxidative stress. Free Radic Biol Med 51:327-336. 52 Rosato E, Kyriacou CP (2006) Analysis of locomotor activity rhythms in Drosophila. Nat Protoc 1:559-568. Rosenzweig ES, Barnes CA (2003) Impact of aging on hippocampal function: plasticity, network dynamics, and cognition. Prog Neurobiol 69:143-179. Saaby L, Jager AK, Moesby L, Hansen EW, Christensen SB (2011) Isolation of immunomodulatory triterpene acids from a standardized rose hip powder (Rosa canina L.). Phytother Res 25:195-201. Sampayo JN, Gill MS, Lithgow GJ (2003) Oxidative stress and aging--the use of superoxide dismutase/catalase mimetics to extend lifespan. Biochem Soc Trans 31:1305-1307. Seelinger G, Merfort I, Schempp CM (2008) Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta Med 74:1667-1677. Senthilkumar K, Elumalai P, Arunkumar R, Banudevi S, Gunadharini ND, Sharmila G, Selvakumar K, Arunakaran J (2010) Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3). Mol Cell Biochem 344:173-184. Shukla S, Maclennan GT, Fu P, Gupta S (2011) Apigenin Attenuates Insulin-Like Growth Factor-I Signaling in an Autochthonous Mouse Prostate Cancer Model. Pharm Res. Simon AF, Liang DT, Krantz DE (2006) Differential decline in behavioral performance of Drosophila melanogaster with age. Mech Ageing Dev 127:647-651. Singh JP, Selvendiran K, Banu SM, Padmavathi R, Sakthisekaran D (2004) Protective role of Apigenin on the status of lipid peroxidation and antioxidant defense against hepatocarcinogenesis in Wistar albino rats. Phytomedicine 11:309-314. Sohal RS, Weindruch R (1996) Oxidative stress, caloric restriction, and aging. Science 273:59-63. Strobel P, Allard C, Perez-Acle T, Calderon R, Aldunate R, Leighton F (2005) Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. Biochem J 386:471-478. Sztanke K, Pasternak K (2003) The Maillard reaction inhibitors and their biological and therapeutic significance. Ann Univ Mariae Curie Sklodowska Med 58:156-158. Thompson KH, Lichter J, LeBel C, Scaife MC, McNeill JH, Orvig C (2009) Vanadium treatment of type 2 diabetes: a view to the future. J Inorg Biochem 103:554-558. Tsai CH, Lo SK, See LC, Chen HZ, Chen RS, Weng YH, Chang FC, Lu CS (2002) 53 Environmental risk factors of young onset Parkinson`s disease: a case-control study. Clin Neurol Neurosurg 104:328-333. Upadhyay K, Gupta NK, Dixit VK (2011) Development and characterization of phyto-vesicles of beta-sitosterol for the treatment of androgenetic alopecia. Arch Dermatol Res. Wang PY, Neretti N, Whitaker R, Hosier S, Chang C, Lu D, Rogina B, Helfand SL (2009) Long-lived Indy and calorie restriction interact to extend life span. Proc Natl Acad Sci U S A 106:9262-9267. Wei H, Tye L, Bresnick E, Birt DF (1990) Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice. Cancer Res 50:499-502. Wei YH, Lu CY, Wei CY, Ma YS, Lee HC (2001) Oxidative stress in human aging and mitochondrial disease-consequences of defective mitochondrial respiration and impaired antioxidant enzyme system. Chin J Physiol 44:1-11. Wilson MA, Shukitt-Hale B, Kalt W, Ingram DK, Joseph JA, Wolkow CA (2006) Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging Cell 5:59-68. Wu SJ, Ng LT, Wang GH, Huang YJ, Chen JL, Sun FM (2010) Chlorophyll a, an active anti-proliferative compound of Ludwigia octovalvis, activates the CD95 (APO-1/CD95) system and AMPK pathway in 3T3-L1 cells. Food Chem Toxicol 48:716-721. Xia S, Miyashita T, Fu TF, Lin WY, Wu CL, Pyzocha L, Lin IR, Saitoe M, Tully T, Chiang AS (2005) NMDA receptors mediate olfactory learning and memory in Drosophila. Curr Biol 15:603-615. Xu B, Li XX, He GR, Hu JJ, Mu X, Tian S, Du GH (2010) Luteolin promotes long-term potentiation and improves cognitive functions in chronic cerebral hypoperfused rats. Eur J Pharmacol 627:99-105. Yamazaki D, Horiuchi J, Nakagami Y, Nagano S, Tamura T, Saitoe M (2007) The Drosophila DCO mutation suppresses age-related memory impairment without affecting lifespan. Nat Neurosci 10:478-484. Yan J, Yang XW (2005) [Studies on the chemical constituents in herb of Ludwigia octovalvis]. Zhongguo Zhong Yao Za Zhi 30:1923-1926. Yang LL, Yen KY, Kiso Y, Hikino H (1987) Antihepatotoxic actions of Formosan plant drugs. J Ethnopharmacol 19:103-110. Young JM, Wessnitzer J, Armstrong JD, Webb B (2011) Elemental and non-elemental olfactory learning in Drosophila. Neurobiol Learn Mem 96:339-352. Zelko IN, Mariani TJ, Folz RJ (2002) Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) 54 gene structures, evolution, and expression. Free Radic Biol Med 33:337-349. Zhang Q, Chang Z, Wang Q (2006) Ursane triterpenoids inhibit atherosclerosis and xanthoma in LDL receptor knockout mice. Cardiovasc Drugs Ther 20:349-357. Zhao Y, Yang G, Ren D, Zhang X, Yin Q, Sun X (2011) Luteolin suppresses growth and migration of human lung cancer cells. Mol Biol Rep 38:1115-1119. Zhong Y, Zuo C, Li F, Ding X, Yao Q, Wu K, Zhang Q, Wang Z, Zhou LW, Lan J, Wang X (1998) [Chemical constituents of Phyllanthus urinaria L. and its antiviral activity against hepatitis B virus]. Zhongguo Zhong Yao Za Zhi 23:363-364, 384. zh_TW
