何首烏之抗微生物與抗氧化活性研究 蘇鵬翰、涂瑞澤、吳淑姿
E-mail: [email protected]
摘 要
何首烏 (Polygonum multiflorum Thunb)為蓼科多年生纏繞性藤本植物之根部，多產於長江以南各省，細長且末端呈現紅褐 色，可助益滋養強壯、益精血、抗衰老、抗病毒與細菌等效用。本研究以水、甲醇或50％乙醇為溶劑輔以熱回流裝置熱液 萃取何首烏，並探討萃取物之抗氧化活性與簡易抗菌試驗，以期開發天然無毒且低劑量之保存試劑。甲醇萃取物在α, α-diphenyl-β-pricrylhydrazyl (DPPH)試驗中，於濃度0.08 mg/mL達到最佳的清除率95.9％；而乙醇萃取物則在還原力、金 屬離子螯合力、清除ABTS 陽離子、抑制硫代巴比妥酸反應產物 (TBARS)之生成，皆可在相對低濃度中達到最佳的抑制效 果。在還原能力試驗中，與標準品butylated hydroxyanisole (BHA)相比，在濃度4.0mg/mL 時可達到最高之150％還原能力。
超氧陰離子試驗中，由於何首烏固有成分：大黃素， 品濃度增加，超氧陰離子之活性越差。在抗微生物試驗中，以甲醇萃 取物在Salmonella typhimurium、Staphylococcus aureus、Escherichia coli、Candida tropicalis 中皆有抑菌環的產生。因此，由 這些試驗判別，何首烏萃取物具有高度抗氧化能力，未來可以此為開發天然無毒之食品添加試劑指標。
關鍵詞 : 何首烏、蓼科、DPPH 試驗、還原力試驗、抗微生物 目錄
封面內頁 簽名頁 中文摘要... iii 英文摘要... iv 誌謝... vi 目錄... vii 圖目
錄... xi 表目錄... xiii 1. 緒 論... 1 1.1 前言... 1 1.2 實驗目 的... 2 2. 文獻回顧... 3 2.1 何首烏之簡 介... 3 2.2 何首烏之主成份... 3 2.2.1 蔥?
類... 5 2.2.2 二苯乙烯類... 5 2.3 何首烏之藥理作 用... 8 2.4 自由基... 13 2.4.1 活性氧化
物... 15 2.4.2 活性氧化物對脂質之傷害... 15 2.4.3 活性氧化物 對DNA之傷害... 19 2.4.4 活性氧化物對蛋白質之傷害... 19 2.4.5 活性氧 化物造成傷害與疾病... 19 2.5 抗氧化之防禦系統... 20 2.5.1 非酵素 性抗氧化劑... 22 2.5.2 酵素性抗氧化劑... 25 2.6 抗微生物物質 之探討... 28 2.6.1 食品保存劑之特性... 30 2.6.2 化學合成之食品 保存劑... 30 2.6.3 天然抗菌物質... 31 3. 材料與方
法... 36 3.1 實驗材料... 36 3.2 何首烏之樣品製 備... 36 3.2.1 何首烏熱回流萃取... 36 3.2.2 何首烏超音波萃 取... 36 3.3 試驗之材料... 37 3.3.1 試驗溶
劑... 37 3.3.2 試驗藥品... 37 3.4 實驗設
備... 38 3.5 實驗架構... 39 3.6 何首烏之抗氧化試 驗... 41 3.6.1 抗氧化成分含量分析... 41 3.6.1.1 總酚化合物含量分 析... 41 3.6.1.2 類黃酮含量測定... 41 3.6.2 抗氧化活性測
試... 41 3.6.2.1 還原力測試... 41 3.6.2.2 清除超氧陰離子試 驗... 42 3.6.2.3 清除DPPH 自由基之測定... 42 3.6.2.4 螯合亞鐵離子之 測定... 43 3.6.2.5 硫代巴比妥酸鹽反映產物之測定... 43 3.6.2.6 清除ABTS 陽離子自由基能力... 44 3.6.3 抗氧化效力評估方法... 44 3.7 何首烏之抗 菌試驗... 45 3.7.1 實驗材料... 45 3.7.2 實驗菌
株... 45 3.7.3 培養基之組成... 45 3.7.4 實驗方 法... 48 3.8 縮寫總表... 49 4. 結果與討 論... 50 4.1 不同萃取時間... 50 4.1.1 萃取
率... 50 4.1.2 總酚與類黃酮含量之分析... 50 4.1.3 清除DPPH 自由基能力... 53 4.2 不同極性之溶劑萃取何首烏... 57 4.3 總類黃酮
與總多酚含量之分析... 57 4.4 清除DPPH 自由基能力... 59 4.5 螯合亞 鐵離子能力... 61 4.6 三價鐵還原力試驗... 61 4.7 超氧陰離子 試驗... 65 4.7 TBARS試驗... 68 4.8 清除ABTS陽離子自 由基... 68 4.9 總抗氧化能力之評估... 71 4.10 抗微生物試 驗... 71 5. 結論... 75 參考文
獻... 76 附錄... 92 圖目錄 圖 2.1 何首烏(a)全 株植物(b)塊根... 4 圖 2.2 ??類之結構式... 6 圖 2.3 二苯乙烯類之結構 式... 7 圖 2.4 利用顯微鏡觀察玻片上之肝細胞內的脂褐質... 10 圖 2.5 乙醯膽鹼 與乙醯膽鹼脂化?的反應式... 10 圖 2.6 大黃素於C6 膠質瘤細胞的分子機制與可能地訊息傳遞路
徑... 12 圖 2.7 細胞防禦抑制活性氧之生成... 14 圖 2.8 大黃素誘導人類癌細胞壞死的訊息 傳遞路徑... 17 圖 2.9 在阿茲海默症中，活性氧化物與脂質、蛋白質、核酸反應並導致細胞的死亡.... 18 圖 2.10 非酵素性抗氧化防禦系統... 23 圖 2.11 酵素性抗氧化防禦系統... 23 圖 2.12 人體內三種不同的超氧歧化?... 27 圖 3.1 實驗架構... 40 圖 4.1 何首烏萃取物清除DPPH自由基能力... 54 圖 4.2 何首烏水萃取物清除DPPH自由基能
力... 55 圖 4.3 何首烏醇類萃取物清除DPPH自由基能力... 56 圖 4.4 何首烏乙酸乙脂
、正己烷及水之音超音波萃取物清除DPPH自由基能力... 60 圖 4.5 何首烏萃取物之螯合能
力... 62 圖 4.6 何首烏萃取物之還原能力... 63 圖 4.7 何首烏萃取物之相 對還原能力... 64 圖 4.8 何首烏萃取物清除超氧陰離子之活性... 66 圖 4.9 ??類之 自氧化循環圖... 67 圖 4.10 何首烏抑制TBARS 的活性... 69 圖 4.11 何首 烏萃取物清除ABTS 陽離子自由基之活性... 70 表目錄 表 2.1 活性氧化物之主要來
源... 16 表 2.2 人體血漿之抗氧化劑... 21 表 2.3 生物安全等級規範及 微生物危險性等級分類... 29 表 2.4 香辛料及藥草之抗菌成份... 33 表 3.1 試驗之 菌株... 46 表 3.2 培養基的組成... 47 表 4.1 何首烏以不同溶 劑和不同時間之萃取率... 51 表 4.2 何首烏以不同溶劑與時間之榭皮素當量與總多酚含量...
52 表 4.3 何首烏以不同溶劑之萃取率、榭皮素當量與沒食子酸當量... 58 表 4.4 何首烏樣品對抗氧化試驗之半清除 濃度或90％清除濃度... 72 表 4.5 何首烏萃取物對4 種微生物之抗菌率... 73
參考文獻
1. 王浴生。1986。何首烏。中藥藥理與運用。10:305-307。 2. 王靜修。1996。何首烏。傳統醫學雜誌。9(1) : 64-67。 3. 李建北、林茂
。1993。何首烏化學成分的研究。中草藥。24: 115-118. 4. 許家津。2003。何首烏萃取物抗氧化性與致突變性之研究。靜宜大學食品營 養研究所碩士論文。 5. 尚志鈞。1999。開寶本草。基層中藥雜誌。第一期。 6. 金國琴、趙佛康。1994。首烏製劑對老年大鼠胸腺、肝 臟蛋白質和核酸含量的影響。中草藥。25(11) :587-589。 7. 唐慎微 著，那琦 編。1976。證類本草。國立編譯館。台北。 8. 陳建霖
。2010。Ergothioneine 對ci splat in 誘導小鼠神經細胞傷害的影響及其作用機制探討。大葉大學生物產業科技研究所碩士論文。 9. 陳曉 光、崔志勇、常一丁、王本祥。1991。何首烏對老年小鼠衰老指標的影響。中草藥。22(8) : 357-358。 10. 陳雅菁。2001。不同濃度何首 烏萃取物對腦神經傳導物質及抗氧化能力之影響。靜宜大學食品營養系碩士論文。 11. 郭悅維。1995。自由基、活性氧與抗氧化劑。台 灣科學 48(2) : 164-177。 12. 張志鵬。2008。刀豆素A誘導細胞自噬在肝癌治療與急性肝炎的作用。國立成功大學基礎醫學研究所博士論 文。 13. 羅宇強。1992。中草藥對大白鼠心臟粒線體脂質過氧化之效果。國立陽明大學傳統醫藥學研究所碩士論文。 14. 趙學敏。1765
。本草綱目拾遺。國立編譯館。台北。 15. 應久皓、周學優、朱秀琴。1992。何首烏炮制品藥理臨床研究。中國中藥雜誌。17(12) : 722-724。 16. 童承福。2007。首烏類中藥有三種。中國醫訊 十月號: 63-67。 17. 戴友平、唐國華、郭衍坤。1998。何首烏提取液對犬心 肌缺血再灌流損傷的預防作用實驗研究。中國生化藥物雜誌。19(2) : 79-80。 18. 錢汝紅、丁鏞發、宋宇紅。1994。首烏對大鼠外周淋巴 細胞DNA 損傷修復能力的影響。上海中醫藥雜誌。4: 41-42。 19. 韓志芬、?文聰。1995。不同首烏提取液對老年大鼠心.肝.腦自由基代 謝及腦內MAO-B 的影響。中國中醫藥科技 2(1) : 36-37。 20. 劉易修。2008。夜交藤與康復力之抗氧化性研究。大葉大學生物產業科技學 系碩士論文。 21. 蔡瑞齡。2009。彩葉草之抗氧化活性及成分分析。大葉大學生物產業科技學系碩士論文。 22. Aebi, H. 1983. Catalase.
In” Methods of Enzymatic Analysis.” p.673-686.Bergmeyer, H. U. Weinhein Deerfield beach. 23. Ahamd, S. 1995. Antioxidant mechanisms of enzymes and proteins. In” Oxidative Stress and Antioxidant Defenses in Biology.” p.240-272. Ahmad, S.Chapman & Hall. International Thomaon Publishing Inc. New York. 24. Amin, N. 1988. Maize production, distribution policy, and the problem of food security in Zimbabwe's communal areas. Development Policy and Practice Research Group, Milton, U.K. 25. Andrads, R. G., Ginani, J. S., Lopes, G. K., Dutra, F., Alonso, A., and Germes-Lima, M. 2006. Tannic acid inhibits in vitro iron-depebdment free radical formation. Biochimie. 88: 1287-1296. 26.
Aruoma, O.I., Spencer, J.P., and Mahmood, N., 1999. Protection against oxidative damage and cell death by the natural antioxidant
ergothioneine. Food Chem. Toxicol. 37: 1043-1053. 27. Aruoma, O.I., Whiteman, M., England, T.G., and Halliwell, B. 1997. Antioxidant action ofergothioneine: assessment of its ability to scavenge peroxynitrite.Biochem. Biophys. Res. Commun. 231: 389-391. 28. Asmus, K. D., Bensasson, R. V., Bernier, J. L., Houssin, R. and Land, E. J. 1996.One electron oxidation of ergothioneine and analogues in vestigated by pluse radiolysis :
redox reactions involving ergothioneine and vitamin C. Biochem. J.315: 635-639. 29. Babbs, C. F. and Steiner, M. G. 1990. Simulation of free radical reactions in biology and medicine : a new two-compartment kinetic model of intracellular lipid peroxidation. Free Radic. Biol. Med. 8:
471-485. 30. Badr, F. M., El-Habit, O. H. M. and Harraz, M. M. 1999. Radioprotective effect of melatonin assessed by measuring chromosomal damage in mitotic and meiotic cells. Mutation Reseach 444: 367-372. 31. Bandopadhyay, U., Dipak, D., and Banerjee, R. K. 1999. Reactive oxygen species: oxidative damage and pathogenesis. Curr. Sci. 77: 658-666. 32. Bhunia, A. K.., Johnson, M. C., Ray, B. and Belden, E. L. 1990.
Antigenic property of pediocin ACH produced by Pediococcus acidilactici H. J. Appl.Microbial. 69: 221-215. 33. Bonorden, W. R. and Pariza, M.
W. 1994. Antioxidant nutrients and protection from free radicals. In: Nutr. Toxicol. Kostsonis, F. N., Mackey, M. and Hjelle, J.ed. Raven press.
New York. p.19-48. 34. Brodo, D., Djjnovic, K. and Bologenesi, M. 1994. Conserved patterns in the Cu,Zn superoxide dismutase family. J. Mol.
Biol. 283: 366-386. 35. Bureau, G., Longpre, F., and Martinoli, M. G. 2008. Resveratrol and quercetin,two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation. J. Neurosci. Res. 86(2): 403-440. 36. Byung, P. Y. 1993. Oxidative damage by free radicals and lipid peroxidation in aging. In” Free Radicals in Aging.” p.59. CRC press. Florida. 37. Cadenas, E. 1995. Mechanisms of oxygen activation and reactive oxygen species detoxification. In” Oxidative Stress and Antioxidant Defenses in Biology.”p.1-25. Ahmad, S. Chapman & Hall.
International Thomaon Publishing Inc. New York. 38. Cai, K., Hagerman, A. E., Minto, R. E., and Bennick, A. 2006. Decreased ployphenol transport across cultured intestinal cells by a salivary proline-rich protein. Biochem. Pharmacol. 71: 1570-1580. 39. Candelario-Jalil, E., de Oliveira, A. C., Graf, S., Bhatia, H.S., Hull, M., Munoz,E., and Fiebich, B. L. 2007. Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia. J. Neuroinflammation. 4: 25. 40. Chan, Y. C., Cheng, F. C., and Wang, M. F. 2002. Beneficial effects of different Polygonum multiflorum Thunb. extracts on memory and hippocampus morphology. J. Nu. Sci.
Vita. 48: 491-497. 41. Chance, B., Sies, H., and Boveris, A. 1979. Hydroperoxide metabolism in mammalian organs. Physiol. Rev. 59: 527-605. 42.
Chander, V., and Chopra, K. 2005. Role of nitric oxide in resveratrol-induced renal protective effects of ischemic preconditioning. J. Vasc. Surg.
42(6):1198-1205. 43. Chander, V., and Chopra, K. 2006a. Protective effect of resveratrol, a polyphenolic phytoalexin on glycerol-induced acute renal failure in rat kidney.Ren. Fail. 28(2): 161-169. 44. Chander ,V., and Chopra, K. 2006b. Protective effect of nitric oxide pathway in resveratrol renal ischemia-reperfusion injury in rats. Arch. Med. Res. 37(1):19-26. 45. Chaudiere, J. and Freeari-Iliou, R. 1999. Intracellular antioxidants : fromchemical to biochemical mechanisms. Food Chem. Toxicol. 37: 949-962. 46. Chauhan, V. and Chauhan, A. 2006. Oxidative stress in Alzheimer’s disease.Pathophysiology 13: 195-208. 47. Chen, Y., Wang, M., Rosen, R. T., and Ho, C. T. 1999. 2.2-Diphenyl-1-picrylhydrazyl radical-scavenging active components from Polygonum multiflorum Thunb. J. Agric. Food Chem. 47: 2226-2228. 48. Cheng, K. C., Cahill, D. S., Kasai, H., Nishimura, S. and Loeb, L. A. 1992.8-hydroxyguanine, an abundant from of oxidative DNA damage, causes GT and AC substitution. J.
Biol. Chem. 267: 166-172. 49. Chu, Y. H., Chang, C. L., and Hsu, H. F. 2000. Flavonoid content of several vegetables and their antioxidant activity. J. Sci. Food Agric. 80: 561-566. 50. Coursin, D. B. Cihla, H. P., Will, J. A. and McCreary, J. L. 1985. Adaptation to chronic hyperoxia.
Biochemical effects and the response to subsequent lethal hyperoxia. Am. J. Physiol. 226: 1401-1407. 51. Csiszar. A., Smith, K., Labinskyy, N., Orosz, Z., Rivera, A., and Ungvari, Z.(2006) Resveratrol attenuates TNF-alpha-induced activation of coronary arterial endothelial cells: role of NF-kappaB inhibition. Am. J. Physiol. Heart Circ.Physiol. 291(4): 1694-1699. 52. Cybulsky, M. I. and Gimbrone, M. A. (1991) Endothelial expression of amononuclear leukocyte adhesion molecule during atherosclerosis. Science. 251:788. 53. Dai, Z., Li, Y., Quarles, L.D., Song, T., Pan, W., Zhou, H., Xiao, Z. 2007.Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation. Phytomedicine.14(12): 806-814. 54. De Almeida, L.M., Pineiro, C.C., Leite, M.C., Brolese, G., Leal, R.B., Gottfried,C., Goncalves, C.A. 2008. Protective effects of resveratrol on hydrogen peroxide induced toxicity in primary cortical astrocyte cultures.
Neurochem. Res. 33(1):8-15. 55. De Jesus Soares, T., Volpini, R. A., Francescato, H. D., Costa, R.S., da Silva, C.G., and Coimbra, T. M. 2007.
Effects of resveratrol on glycerol-induced renal injury. Life Sci. 81(8): 647-656. 56. Do Amaral, C. L., Francescato, H. D., Coimbra, T. M., Costa, R. S., Darin, J. D.,Antunes, L. M., and Bianchi, M. D. 2007. Resveratrol attenuates cisplatin-induced nephrotoxicity in rats. Arch. Toxicol. 82(6):
363-370. 57. Dong, W., Gao, D., Lin, H, Zhang, X., Li, N., and Li, F. 2008. New insights into mechanism for the effect of resveratrol
preconditioning against cerebral ischemic stroke: Possible role of matrix metalloprotease-9. Med. Hypotheses. 70(1): 52-55. 58. Duh, P.D., Yen, G.C, Yen, W.J., Wang, B.S., Chang, L.W. 2004. Effects of pu-erh tea on oxidative damage and nitric oxide scavenging. J. Agric. Food Chem. 52:
8169-8176. 59. Dunn, E. T., Grandmasion, E. W., and Goosen, M. F. A. 1997. Application and properties of chitosan. Applications of chitin and chitosan, Technomic Publishing, Lancaster, USA, p.3-29. 60. Ekshyyan, V.P., Hebert, V.Y., Khandelwal, A., and Dugas, T.R. 2007. Resveratrol inhibits rat aortic vascular smooth muscle cell proliferation via estrogen receptor dependent nitric oxide production. Cardiovasc Pharmacol. 50(1):
83-93. 61. Encinas, M. V., Lissi, E. A. and Olea, A. F. 1985. Quenching of triplet benzophenone by vitamins E and C and by sulfur containing amino acids and peptides. Photochem. Photobiol. 42: 347-352. 62. Fita and Rossman 1985. The NADPH binding site on beef liver catalase.
Proc.Natl. Acad. Sci. U S A. 82(6): 1604-1608. 63. Frankel, E. N. 1991. Recent advances in lipid oxidation. J. Sci. Food Agric. 54:495-511. 64.
Gao, Z.B., Chen, X.Q., and Hu, G.Y. 2006. Inhibition of excitatory synaptic transmission by trans-resveratrol in rat hippocampus. Brain Res.
1111(1): 41-47. 65. Gerrity, R. G. 1981. The role of the monocyte in atherogenesis: transition of blood-borne monocytes into foam cells in fatty lesions. Am. J. Pathol. 103: 181. 66. Gledhill, J.R., Montgomery, M.G., Leslie, A.G., Walker, J.E. 2007. Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols. Proc.Natl. Acad. Sci. USA. 104(34): 13632-13637. 67. Goosen, M. F. A. 1997. Applications of chitin and chitosan, Technomic Pulishing,Lancaster, USA, p.117-143. 68. Gould, D. G. W. 1996. Natrual antictobials from plants. New Method of Food Preservation. Springer. 40: 57. 69. Green, M. J. and Hill, H. A. 1984. Chemistry of dioxygen. Methods Enzymol.105: 3-22. 70. Hagrman, D.,
Goodisman, J., Dabrowiak, J.C., Souid, A.K., 2003. Kinetic study on the reaction of cisplatin with metallothionein. Drug Metab. Dispos.
31:916-923. 71. Halliwell, B. 1987. Oxidants and human disease: some new concepts. Faseb. J.1: 358-364. 72. Halliwell, B. and Aruoma, O. I.
1992. DNA damage by oxygen-derived species.In” Molecular Biology of Free Radicals Scavenger System.”Scandalios, J. G.p.47-67. Cold Spring Harbor Laboratory Press. New York. 73. Halliwell, B. and Gutteridge, J. M. C. 1998. Free radicals in biology and medicine. Oxford University Press. New York, p.548-549. 74. Harman, D. 1957. Atherosclerosis : a hypothesis concerning initiating steps in pathogenesis. J. Gerontol. 12: 199.
75. Harman, D. 1986. Free radical theory of aging. Role of free radicals in the origination and evolution of life, aging, and disease processes. “In Free radicals,Aging, and Degenerative Diseases.” p.3. Johnson, J. E., Jr., Walford, R., Harman,D. and Miqued, J. Alan R. Liss. New York. 76.
Hartman, P. E. 1990. Ergothioneine as an antioxidant. Meth. Enzymol. 259:310-318. 77. Hata, K., Kozawa, M. & Baba, K. 1975. New stilbene glucoside from Chinese crude drug Heshouwu, roots of Polygonum multiflorom. Yakugaku Zasshi 95:211-213. 78. Hong, C. Y., Lo, Y. C., Tan, F.
C., Wei, Y. H. and Chen, C. F. 1994. Astragalus membranaceus and Polygonum multiflorum protect rat heart mitochondria against lipid peroxidation. Am. J. Chin. Med. 22: 63-70. 79. Hsu, C.Y. 2006. Antioxidant activity of extract from Polygnum aviculare. Biol.Res. 39: 281-288.
80. Hsu, C. Y., Chan, Y. P. and Chang, J. 2007. Antioxidant activity of extract from Polygonum cuspidatum. Biol. Res. 40: 13-21. 81. Hwang, I.K., Yoo, K. Y., Kim, D. W., Jeong, S.J., Won, C. K., Moon, W. K.,im, Y. S., Kwon, D. Y., Won, M. H. and Kim D. W. 2006. An extract of Polygonum multiflorum protects against free radical damage induced by ultra violet B irradiation of the skin. Braz. J. Med. Biol. Res. 39:
1181-1188. 82. Igarashi, M., Ishibashi, T., Nishihira, J., and Tachikawa, H. 2003. Energetics of Catalytic Reaction of Acetylcholinesterase (AchE) with Acetylcholine (ACh):Role of the Oxyanion Hole. Int. Elec. J. Molecular Design. 2: 712-722. 83. Imlay, J. A. and Linn, S. 1988. DNA damage and oxygen radical toxicity.Science. 240: 1302. 84. Jocelyn, P. C. 1971. Biochemistry of the SH Group. Academic Press, New York. 85. Johansson, J., Cederlund, E., Moodbidri, S. B., Sheth, A., Jornvall, H. 1986.Superoxide dismutase in human testis preparations. Biosci. Rep. 6(6):535-541. 86.
Jonas, N. and Elias, S. J. 2001. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radical Biol. 31(11):
1287-1312. 87. Kaur, P. and Arona, S. 2010. Polyphenols of caeselpiniaceae. J. Chi. Med. 5(5):282-290. 88. Keaney, J.R. and Frei, B. 1994.
Antioxidant protection of low-density lipoprotein and its role in the prevention of atherosclerotic vascular disease. In "Nature Antioxidants in Human Health and Disease." Ed. By B. Frei, p.303-351. Academic Press: San Diego, CA. 89. Kim, M. S., Park, M. J., Kim, S. J., Lee, C. H., Yoo, H., Shin, S. H., Song, E. S.,and Lee, S. H. 2005. Emodin suppresses hyaluronic acid-induced MMP-9 secretion and invasion of glioma cells. Int. J.
Oncol. 27(3): 839-846 90. Kim, Y. A., Kim, G. Y., Park, K. Y., and Choi, Y. H. 2007. Resveratrol inhibits nitric oxide and prostaglandin E2 production by lipopolysaccharide-activated C6 microglia. J. Med. Food. 10(2): 218-24. 91. Kim, Y. A., Rhee, S. H., Park, K. Y., and Choi,Y. H.
2003. Antiproliferative effect of resveratrol in human prostate carcinoma cells. J. Med. Food. 6(4): 273-280. 92. Kumar, P., Padi, S.S., Naidu, P.S., and Kumar, A. 2006. Effect of resveratrol on 3-nitropropionic acid-induced biochemical and behavioural changes: possible neuroprotective mechanisms. Behav. Pharmacol. 17(5-6): 485-492. 93. Kuo, T. C., Yang, J. S., Lin, M. W., Hsu, S. C., Lin, J. J., Lin, H. J. Hsia, T. C.,Liao, C. L., Yang, M. D., Fan, M. J., Wood, W. G., and Chung, J. G. 2009. Emodin has cytotoxic and protective effects in rat C6 glioma cells: Roles of mdr1a and nuclear factor B in Cell Survival. J. pharmacology and experimental therapeutics 330(3): 736-744. 94. Li, X., Matsumoto, K., Murakami, Y., Tezuka, Y., Wu, Y. L., and Kadota, S. 2005. Neuroprotective effects of Polygonum multiflorum on nigrostriatal dopaminergic degeneration induced by paraquat and maneb in mice. Pharm. Biochem. Beh. 82: 345-352. 95. Li, Z., Li, L. J., Sun, Y., Li, J. 2007. Identification of natural compounds with anti-hepatitis B virus activity from Rheun plamatum L. ethanol extract.Chemotherapy. 53: 320-326. 96. Lisbeth, T. H., John, W.
A., and Tom, A. G. 2001. Antibacterial effect of protamine in combination with EDTA and refrigeration. Int. J. Food Microbial.66: 149-161. 97.
Liu, Q. L., Xiao, J. H., Ma, R., Ban. Y., and Wang. J. L. 2007. Effect of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-d-glucoside on lipoprotein oxidation and proliferation of coronary arterial smooth cells. J. Asian Nat. Prod. Res. 9(5):421-429. 98. Liu, Z. P., Li, W. X., Yu, B., Huang, J., Sun. J., Huo, J. S., and Liu, C. X. 2005.Effects of trans-resveratrol from Polygonum cuspidatum on bone loss using the ovariectomized rat model. J.
Med. Food. 8(1): 14-19. 99. Lu, C. C., Yang, J. S., Huang, A. C., Hsia, T. C, Chou, S. T., Kuo, C. L., Lu, H.F., Lee, T. H., Wood, W. G., and Chung, J. G. 2010. Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells.
Mol. Nutr. Food Res. 54: 1-10. 100. Lu, K.T., Chiou, R.Y., Chen, L.G., Chen, M.H., Tseng, W.T., Hsieh, H.T., Yang,Y.L. 2006.
Neuroprotective effects of resveratrol on cerebral ischemia-induced neuron loss mediated by free radical scavenging and cerebral blood flow elevation. J. Agric. Food Chem. 54(8): 3126-3131. 101. Ma, X., Tian, X., Huang, X., Yan, F., and Qiao, D. 2007. Resveratrol-induced mitochondrial dysfunction and apoptosis are associated with Ca2+ and mCICR-mediated MPT activation in HepG2 cells. Mol. Cell Biochem.
302(1-2):99-109. 102. Melville, D. B. 1959. Ergothioneine. Vitamin Horm. XVII: 155-204. 103. Mencherini, T., Picerno, P., Scesa, C., and Aquino, R. 2007. Triterpene,antioxidant, and antimicrobial compounds from Caesalpina officinalis. J. Nat.Prod. 70: 189-1894. 104. Mendonca, L.M., Dos Santos, G.C., Antonucci, G.A., Dos Santos, A.C., Bianchi Mde, L., and Antunes, L.M. 2009. Evaluation of the cytotoxicity and genotoxicity of curcumin in PC12 cells. Mutat. Res. 675: 29-34. 105. Menedez-Palaez, A., Poeggeler, B., Reiter, R. J., Walden, L. R. B., Pablos, M.
I.and Tan, D. X. 1993. Nuclear localization of melatonin in different mammalian tissues : immunocytochemical and radioimmunoassay evidence.
J. Cell Biolchem. 53: 372-382. 106. Mijatovic, S., Maksimovic-Ivanic, D., Radovic, J., Miljkovic, D. J., Harhaji, L.J., Vuckovic, O., Stosic-Grujicic, S., Mostarica Stojkovic, M., and Trajkovic, V.2005. Anti-glioma action of aloe emodin: the role of ERK inhibition. Cell Mol.Life Sci. 62(5):
589-98. 107. Morrissey, P. A. and O’Brien, N. M. 1998. Dietary antioxidants in health and disease. Int. Dairy J. 8: 463-472. 108. Nakatani, N.
1997. Antioxidants from spices and herbs. In “Natural Antioxidants Chermistry, Health Effects, Applications.” Shahidi, F. Ed., New
Foundland.Canda. p. 64-75. 109. Niki, E. 1992. Active oxygens and free radicals in biology. J. Jpn. Oil. Chem.Soc. 41: 768-773. 110. Niwa, Y. and
Miyachi, Y. 1986. Antioxidant action of natural health products and chinese herbs. Inflammation. 10: 79-91. 111. Nobuhiko. T., Tadayoshi. S., Koji, M., Hisao K. 1995. Molecular cloning of thedefense factor in the albumen gland of the sea hare Aplysia kurodai. Febs let. 377: 373-376. 112.
Okatani, Y., Wakatsuki, A., Morioka, N., and Watanabe, K. 1999. Melatonin inhibits the vasorelaxant action of peroxynitrite in human umbilical artery. J. Pineal. Res. 27: 111-115. 113. Peng, X., Cheng, K. W., Ma, J., Chen, B. Ho, C. T., Lo, C., Chen, F., and Wang,M. 2008. Cinnamon bark proanthocyanidins as reactive carbonyl scavengers to prevent the formation of advanced glycation endproducts. J. Agric. Food Chem.56:
1907-1911. 114. Pierrefiche, G. and Laborit, H. 1995. Oxygen free radicals, melatonin and aging.Exp. Gerontol. 30: 213-227. 115. Ramarathnam, N., Osawa, T., Namiki, M., and Kawakishi, S. 1989. Chemical studies on novel rice hull antioxidants. 2. Identification of isovitexin, a c-glycosyl flavonoid. J. Agric. Food Chem. 37: 316-319. 116. Raval, A. P., Dave, K. R., and Perez-Pinzon, M. A. 2006. Resveratrol mimics ischemic preconditioning in the brain. Cereb Blood Flow Metab. 26(9):1141-1147. 117. Reiter, R. J. 1993. Interactions of the pineal hormone melatonin with oxygen-centered free radicals : a brief review. Braz. J. Med. Biol. Res. 26(1):1141-1155. 118. Reiter, R. J. 1995a. Functions pleiotropy of the neurohormone melatonin:antioxidant protection and neuroendocrine regulation. Front. Neuroendocrinol.16(4): 383-415. 119. Reiter, R. J. 1995b.
Functions pleiotropy of the neurohormone melatonin:antioxidant protection and neuroendocrine regulation. Front. Neuroendocrinol.16: 383. 120.
Reiter, R. J. 1998. Oxidative damage in the central nervous system : by melatonin. Prog . Neurobiol. 56: 359-384. 121. Rhoades, J. and Roller, S.
2000. Antimicrobial actions of degraded and native chitosan against spoilage organisms in laboratory media and foods. Appl. Environ. Microbial.
66(1): 80-86. 122. Ripa, F. A., Haque, M and Bulbul, I. J. 2010. In vitro Antibacterial, Cytotoxic and Antioxidant Activities od Plant. Nephelium Iongan. Pak. J. Biol. Sci. 13(1):22-27. 123. Sano, M., Ernesto, C., Thomas, R. G., Klauber, M. R., Schafer, K., Grundman,M., Woodbury, P., Growdon, J., Cotman, C. W., Pfeiffer, E., Schneider, L. S.,and Thal, L. J., 1997. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study.New Eng. J. Med. 336: 1216-1222. 124. Sato, M.,
Ramarathnam, N., Suzuki, Y., Ohkubo, T., Takeuchi, M. and Ochi, H.1996. Varietal differences in the phenolic content and superoxide radical scavenging potential of wines from different sources. J. Agric. Food Chem. 44:37-41. 125. Sengottuvelan, M., Senthilkumar, R., and Nalini, N.
2006. Modulatory influence of dietary resveratrol during different phases of 1,2-dimethylhydrazine induced mucosal lipid-peroxidation, antioxidant status and aberrant crypt foci development in rat colon carcinogenesis. Biochim. Biophys. Acta. 1760(8): 1175-1183. 126. Sharma, S., Kulkarni, S.K., and Chopra, K. 2007. Effect of resveratrol, a polyphenolic phytoalexin, on thermal hyperalgesia in a mouse model of diabetic neuropathic pain. Fundam. Clin. Pharmacol. 21(1): 89-94. 127. Shires, T. K., Brummel, M. C., Pulido, J. S., and Stegink, L. D. 1997.Ergothioneine distribution in bovine and porcine ocular tissues. Comp. Biochem.Physiol. C Pharmacol. Toxicol. Endocrinol. 117: 117-120. 128. Simic, M. G. 1988.
Mechanisms of inhibition of free-radical processes in mutagenesis and carcinogenesis. Mutat. Res. 202: 377-386. 129. Skjak, B. G., Anthonsen, T., and Sandford, P. 1989. Chitin and chitosan. Elsevier Applied Science, London, p.560. 130. Song, L. H., Pan, W., Yu, Y. H., Quarles, L. D., Zhou, H. H., and Xiao, Z. S. 2006. Resveratrol prevents CsA inhibition of proliferation and osteoblastic differentiation of mouse bone marrow-derived mesenchymal stem cells through an ER/NO/cGMP pathway. Toxicol In Vitro. 20(6): 915-922. 131. Song, T. Y., Chen, C. L., Liao, J. W., Ou, H.
C., and Tsai, M. S. 2010.Ergothioneine protects against neuronal injury induced by cisplatin both in vitro and in vivo. Food chemtox. 48:
3492-3499. 132. Srivastava, A. K., Bhargava, P., Thapar, R., Rai, L. C. 2009. Differential response of antioxidative defense system of Anabaena doliolum under arsenite and arsenate stress. J. Basic Microbiol. 49(1): 63-72. 133. Stadtman, E. R. 1992. Protein oxidation and aging. Science.
257(28): 1220-1224. 134. Stutz, J. 2004. “Radical chemistry in the nocturnal boundary layer: Observations and modeling studies”, Telluride Workshop on Atmospheric Radicals. 135. Stutz, J. R., Ackermann, J. D. Fast, A., and Barrie, L. A. Atmospheric reactive chlorine and bromine at the Great Salt Lake, Utah, Geophys. Res. Lett. 29(10):2002. 136. Tan, D. X., Chen, D., Poeggeler, B., Manchester, L. C., and Reiter, R. J. 1993.
Melatonin: a potent endogenous hydroxyl radical scavenger. Endocr. J. 1: 57-60. 137. Tang, T., Yin, L., Yang, J., and Shan, G. 2007. Emodin, an anthraquinone derivative from Rheum officinale Baill, enhances cutaneous wound healing in rats. Eur. J. Pharmacol. 567(3): 177-185. 138.
Terman, A. and Brunk, U. T. 2004. Lipofuscin. Int J Biochem Cell Biol 36(8):1400-1404. 139. Tsai, S., Hung, L. M., Fu, Y. T., Cheng, H., Nien, M. W., Liu, H. Y., Zhang, F.B., and Huang, S. S. 2007. Resveratrol neuroprotective effects during focal cerebral ischemia injury via nitric oxide mechanism in rats. J. Vasc. Surg. 46(2): 346-353 140. Um, M. Y., Choi, W. H., Aan, J. Y., Kim, S. R., and Ha, T. Y. 2006. Protective effect of Polygonum multiflorum Thunb on amyloid-peptide 25-35 induced cognitive deficits in mice. J. Ethnopharm. 104: 144-148. 141. Van den Broeke, L. T. and Beyersbergen van Henegouwen, G. M. 1993. Thiols as potential UV radiation protectors : an in vitro study. J. Photochem.
Photobiol.Biol. 17: 279-286. 142. Wang, C. H., Gao, Z. Q., Ye, B., Cai, J.T., Xie, C. G., Qian, K. D., and Du, Q. 2007. Effect of emodin on pancreatic fibrosis in rats. World J Gastroenterol.13(3): 378-82. 143. Xia, X. M., Wang, F.Y., Wang, Z. K., Wan, H. J., Xu, W,A., and Lu, H.
2010.Emodin enhances alveolar epithelial barrier function in rats with experimental acute pancreatitis. World J. Gastroenterol. 16(24): 2994-3001.
144. Yang, J., He, R., Gao, F., Sang, H., Tang, X., and Ye, R. D. 2004. Emodin enhances arsenic trioxide-induced apoptosis via generation of reactive oxygen species and inhibition of survival signaling. Cancer Res. 64(1): 108-116. 145. Yan, J. J., Cho, J. Y., Kim, H. S., Kim, K. L., Jung, J.
S., Huh, S. O., Suh, H. W.,Kim, Y. H., and Song, D. K. 2001. Protection against β-amyloid peptide toxicity in vivo with long-term administration of ferulic acid. British Journal of Pharmacology 133: 89-96. 146. Yim, T. K., Wu, W.K., Mak, D. H., and Ko, K. M. 1998.
Myocardial protective effect of an anthraquinone-containing extract of Polygonum multiflorum ex vivo.Planta. Med. 64: 607-611. 147. Yu, H., Pan, C., Zhao, S., Wang, Z., Zhang, H., and Wu, W. 2007. Resveratrol inhibits tumor necrosis factor-α-mediated matrix metalloproteinase-9 expression and invasion of human hepatocellular carcinoma cells. Biomed. Pharmacother.1(4): 285-290. 148. Yun, K. J., Min, B. S., Kim, J.Y., and Lee, K. T. 2007. A isolated fom the stem bark of Styax japonica inhibits lipopolysacaharide-induced expression of inducible nitric oxide synthase
and cyclooxygenase-2 in RAW 264. 7 cells by suppressing nuclear factor-kappa B activation. Biol. Pharm. Bull. 30: 139-144. 149. Zeashana, H., Amresha, G., Singhb, S., and Rao, C. V. 2009. Hepatoprotective and antioxidant activity of Amaranthus spinosus against CCl4 induced toxicity.
J.Ethpharm. 125: 364-366. 150. Zhang, C., Teng, L., Shi, Y., Jin J, Xue, Y., Shang, K., and Gu, J. 2002. Effect of emodin on proliferation and differentiation of 3T3-L1 preadipocyte and FAS activity. Chin. Med. J. 115(7): 1035-1038. 151. Zhang, H., Jeong, B. S., and Ma, T. H. 1999.
Antimutagenic property of an herbal medicine, Polygonum multiftorum Thunb. detected by the Tradescantia micronucleus assay. J. Environ.
Pathol. Toxicol. Oncol. 18(2): 127-130. 152. Zhang, L., Lau, Y. K., Xi, L., Hong, R. L., Kim, D. S., Chen, C. F., Hortobagyi,G. N., Chang, C., and Hung, M. C. 1998. Tyrosine kinase inhibitors, emodin and its derivative repress HER-2/neu-induced cellular transformation and
metastasis-associated properties. Oncogene. 16(22): 2855-2863. 153. Zhang, Y. Z., Shen, J. F., Xu, J. Y., Xiao, J. H., Wang, J. L. 2007. Inhibitory effects of 2,3,5,4'-tetrahydroxystilbene-2-ο-β-d-glucoside on experimental inflammation and cyclooxygenase 2 activity. J. Asian Nat. Prod. Res.
9(4):355-363. 154. Zhang, Z., Liao, L., Moore, J., Wu, T., and Wang, Z. 2009. Antioxidant phenolic compounds from walnut kernels (Juglans regia L.) Food Chem. 113: 160-165.
