臺灣博碩士論文加值系統

中文摘要
山藥自古以來，無論在東、西方均被視為有益健康的食品或藥品，所以山藥的各種營養成分非常值得被深入研究與開發。本研究以省產三種不同品種山藥 (Dioscorea spp.)為材料，包含台農一號（TN1）、台農二號（TN2）、名間長紅山藥（MJ），抽取並經過部分純化（包括SDS沉澱及鈣離子沉澱去除）後所得黏質多醣（Mucilage）來作抗氧化及免疫調節活性之研究。在評估山藥黏質多醣抗氧化活性時，所測試的項目包括DPPH自由基清除、氫氧自由基清除、超氧自由基清除、抗低密度脂蛋白氧化，並以ESR進行氫氧自由基清除實驗。實驗結果顯示，不同品種山藥之黏質多醣均具有抗氧化能力，而純化過後黏質多醣之抗氧化能力較佳。評估山藥黏質多醣的免疫調節功效時，則使用動物模式（BALB/c小白鼠）進行測試，分別給予三種純化過之黏質多醣和香菇多醣（作陽性對照）來作比較。本研究以流式細胞儀（flow cytometry）作為測試非特異性免疫活性（innate immunity）之技術平台，其中包含淋巴細胞亞群的分佈、顆粒性白血球和單核球細胞的吞噬作用、自然殺手細胞活性的分析。同時亦測試山藥黏質多醣對老鼠腹腔巨噬細胞與巨噬細胞株（RAW264.7）體外吞噬作用之影響。而特異性免疫活性之評估則以OVA抗原（ovalbumin）免疫老鼠後，利用ELISA分析專一性抗體產生濃度的高低；並以MTT定量法測試老鼠脾臟細胞受OVA刺激後的分裂能力。結果顯示在第一週時，TN2及MJ組老鼠周邊血液中T cell（CD3＋）總數顯著增加（p＜0.01），而其中增加的又以輔助T細胞（T helper cell, CD4＋）（p＜0.05）為最顯著，Cytotoxic T cell (CD8＋)的比率則無顯著性變化。TN2及MJ組的B cell (CD19＋)比率則相對顯著減少（p＜0.01）。而第三週時僅MJ組的T cell（CD3＋）總數有顯著性增加（p＜0.01），B cell (CD19＋)比率有相對顯著減少（p＜0.01）。而BALB/c小白鼠周邊血液中單核球細胞的吞噬能力在第一週時MJ組（p＜0.05）、TN1和TN2組（p＜0.01）有顯著性增加，而顆粒性白血球的吞噬能力則皆無明顯變化。但至第三週時，四種樣品皆顯著促進顆粒性白血球之吞噬能力；而單核球細胞之吞噬能力除TN2組外其餘三種樣品皆呈顯著增加。而四種樣品在試管中亦均能促進老鼠腹腔巨噬細胞與巨噬細胞株（RAW264.7）之吞噬能力。自然殺手細胞毒殺能力的測定結果發現：Effector cell和Target cell比例從5：1至40：1時，MJ組自然殺手細胞毒殺能力均比對照組有顯著增加（p＜0.01），而其他二組（TN1、TN2）和對照組比較，自然殺手細胞毒殺能力雖有增加但較不明顯。以OVA抗原免疫BALB/c小白鼠後，結果發現香菇多醣和三種山藥黏質多醣皆可促進專一性抗OVA抗體IgG和IgM之生成，而其中以TN1和香菇多醣效果較顯著。比較OVA免疫後老鼠的脾臟細胞在OVA抗原刺激後之分裂能力，亦發現香菇多醣和三種山藥黏質多醣組老鼠脾臟細胞增生的能力均較對照組強。

Abstract
The yam（Dioscorea spp）has been widely used as food and remedy in China and Western countries. It has been reported to have a lot of bioactive substances for promotion of health and longevity, and is worthy to be further studied. In this study, the crude extracts of yam tuber of Dioscorea alata L.cv.Tainong 1 (Tainong no.1 yam；TN1)、Dioscorea alata L.cv.Tainong 2 (Tainong no.2 yam；TN2) and D. alata L.var. purpurea (Roxb.) Ming.Jen（MJ）were precipitated with SDS and removal of CaCl2 precipitates to get the partially purified mucilage polysaccharides. For evaluating the antioxidant effects of the mucilage polysaccharide, a series of in vitro tests, including DPPH radical scavenging activity assay, hydroxyl radical scavenging activity assay, superoxide radicals scavenging activity, anti-human low density lipoprotein (LDL) oxidation test, and hydroxyl radical scavenging activity assay by electron spin resonance（ESR）spectrometry were detected. The results demonstrated that different species of yams exhibited different antioxidant ability, and the purification process could increase the antioxidant activity of the mucilage polysaccharide. Taken together, our results suggest that mucilage polysaccharides of the yam tuber might play an important role on antiradicals and antioxidants. For determining and comparing the immunomodulating effects of the yam mucilage polysaccharide of the three species, the innate and adaptive immunity were evaluated on the BALB/c mice. BALB/c mice were assigned to five groups：group TN1, TN2 and MJ were daily, orally administrated with 0.5 ml mucilage polysaccharide （10 mg / ml） separately for 5 weeks. Group Lentinan（Len） was the positive control group and fed with purified Lentinan（0.05 mg / ml）. Blood samples were drawn from the retroorbital sinus on day 7 and 21, and the flow cytometry was used to analyze the lymphocyte subpopulation, phagocytosis of granulocyte and monocyte. In addition, the stimulating indexes of mucilage polysaccharide on the phagocytosis of peritoneal macrophages and the RAW264.7 cell line were also determined by in vitro assay. Our results demonstrated that the ratio of T helper cells in the peripheral blood of groups TN1, TN2 and MJ increased significantly, especially Group MJ. All three kinds of mucilage polysaccharide could enhance the phagocytic activity of granulocyte, monocytes and macrophages both in vivo and in vitro tests. On day 36, the mice were sacrificed, and the splenocytes were harvested for analysis of Nature killer cell cytotoxicity. The natural killer cells of Group MJ had better cytotoxic activity than the other samples. In the evaluating of specific immunity, we found that the production of specific anti-OVA antibody and proliferation of splenocytes after specifically stimulating with OVA were also enhanced on mucilage groups. In summary, oral administration of yam tuber mucilage for 5 weeks may enhance the innate and adaptive immunity.

目錄
目錄…………………………………………………………………….….I
圖目錄……………………………………………………………………IV
中文摘要…………………………………………………………………1
英文摘要…………………………………………………………………3
前言………………………………………………………………………5
文獻蒐集…………………………………………………………………6
一、 山藥…………………………………………………………..6
二、 多醣體與抗氧化機能概說…………………………………10
三、 免疫機能概說………………………………………………14
四、 多醣體與免疫調節活性概說………………………………15
五、 保健食品概況簡介…………………………………………18
實驗材料與方法...……………………………………………………...20
山藥黏質多醣抗氧化活性的評估………….…………………………20
一、 山藥黏質多醣之粗取…………………………………….20
二、 山藥黏質多醣之純化……………………………………..22
三、 DPPH自由基清除試驗…………………………………..24
四、 氫氧自由基自由基清除試驗……………………………..25
五、 超氧自由基清除試驗……………………………………..27
六、 抗低密度脂蛋白氧化力………………………………..…28
七、 ESR測定氫氧自由基實驗…………………………….…30
山藥黏質多醣免疫調節活性的評估…………………………………..32
山藥黏質多醣對BALB/c小白鼠特異性免疫能力的影響…………..32
BALB/c小白鼠非特異性免疫能力測定………………………………33
一、 周邊血中淋巴細胞亞群分布……………………………..33
二、 周邊血中多形核白血球和單核球之吞噬作用…………..37
三、 自然殺手細胞毒殺能力…………………………………..41
四、 試管中山藥黏質多醣對巨噬細胞吞噬作用的影響……..46
山藥黏質多醣對BALB/c小白鼠特異性免疫能力的影響…………...50
BALB/c小白鼠特異性免疫能力測定…………………………………51
一、 ELISA方法測定免疫後老鼠血液中專一性抗體的濃度…50
二、 OVA刺激脾臟細胞增生之測定……………………………54
結果與討論………………………………………………………………56
山藥黏質多醣抗氧化活性結果與討論…………………………………57
一、 DPPH自由基清除試驗……………………………………..57
二、 氫氧自由基清除試驗………………………………………..59
三、 超氧自由基清除試驗………………………………………..62
四、 抗低密度脂蛋白氧化能力…………………………………..64
山藥黏質多醣免疫調節活性之結果與討論…………………………..78
一、 淋巴細胞亞群分布………………………………………….78
二、 多形核白血球及單核球細胞的吞噬作用…………………..80
三、 山藥黏質多醣對老鼠腹腔液巨噬細胞和巨噬細胞株
RAW264.7吞噬作用的影響……..………………………...82
四、 自然殺手細胞毒殺能力……………………………………..84
五、 山藥黏質多醣對BALB/c小白鼠分泌抗OVA專一性抗體的影響…………………………………………………………..86
六、 山藥黏質多醣對BALB/c小白鼠脾臟細胞受OVA抗原專一性刺激後細胞增生的影響…………………………………..88
結論……………………………………………………………………..102
參考文獻…………………………………………………………..……103
附錄……………………………………………………………………..113
圖目錄
圖一、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之山薬黏質多醣對於DPPH自由基清除能力強弱之測定圖。（A）未經純化前（B）經過純化……………………………….65、66
圖二、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之山薬黏質多醣對於純化前與純化後之DPPH自由基清除能力之IC50比較 ………………………...………………………………67
圖三、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之山薬黏質多醣對於氫氧自由基清除能力強弱之測定圖。（A）未經純化前（B）經過純化…………………………………68、69
圖四、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之
山薬黏質多醣對於純化前與純化後之氫氧自由基清除能力之IC50比較…………….…………………………………………..70
圖五、三種山薬黏質多醣以ESR偵測清除清氧自由基能力強弱圖
（A）台農一號（TN1）（B）台農二號（TN2）（C）名間長紅（MJ）………...……………………………………………71、72
圖六、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之山薬黏質多醣對於超氧自由基清除能力強弱之測定圖。（A）未經純化前（B）經過純化………………………………….73、74
圖七、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之
山薬黏質多醣對於純化前與純化後之超氧自由基清除能力
IC50比較……………….………………………………………..75
圖八、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之山薬黏質多醣對於抗低密度脂蛋白氧化能力強弱之測定圖。（A）未經純化前（B）經過純化………………………………76、77
圖九、口服香菇多醣（Len）、台農一號（TN1）、台農二號（TN2）、
與名間長紅（MJ）之山藥黏質多醣一週後，對於BALB/c老鼠血液淋巴細胞亞群分布（T cell and B cell）之影響…………90
圖十、口服香菇多醣（Len）、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之山藥黏質多醣三週後，對於BALB/c老鼠血液淋巴細胞亞群分布（T cell and B cell）之影響………...91
圖十一、口服香菇多醣（Len）、台農一號（TN1）、台農二號（TN2）、
與名間長紅（MJ）之山藥黏質多醣一週後對老鼠血液淋巴細胞亞群分布（T help cell and Cytotoxic T cell）之影響………..92
圖十二、口服香菇多醣（Len）、台農一號（TN1）、台農二號（TN2）、
與名間長紅（MJ）之山藥黏質多醣三週後對老鼠血液淋巴細胞亞群分布（T help cell and Cytotoxic T cell）之影響……...…93
圖十三、口服香菇多醣（Len）、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之山藥黏質多醣一週後對老鼠週邊血液多形核白血球及單核球細胞吞噬能力之影響…………………..94
圖十四、口服香菇多醣（Len）、台農一號（TN1）、台農二號（TN2）、
與名間長紅（MJ）之山藥黏質多醣三週後對老鼠週邊血液多形核白血球及單核球細胞吞噬能力之影響…………………..95
圖十五、口服香菇多醣（Len）、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之山藥黏質多醣對於老鼠腹腔液巨噬細胞吞噬能力之影響…………………………………………..96
圖十六、口服香菇多醣（Len）、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之山藥黏質多醣對於老鼠巨噬細胞株RAW264.7吞噬能力之影響…………………………………97
圖十七、口服香菇多醣（Len）、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之山藥黏質多醣五週後對老鼠自然殺手細胞毒殺能力之影響………………………………………..98
圖十八、口服香菇多醣（Len）、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之山藥黏質多醣對於老鼠以OVA刺激脾臟細胞增生能力變化………………………………………..99
圖十九、口服香菇多醣（Len）、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之山藥黏質多醣後對於OVA免疫老鼠產生抗OVA專一性抗體 IgG的影響………………………..100
圖二十、口服香菇多醣（Len）、台農一號（TN1）、台農二號（TN2）、與名間長紅（MJ）之山藥黏質多醣後對於OVA免疫老鼠產生抗OVA專一性抗體 IgM的影響……………………….101

參考文獻
陳詩詩。2001。以免疫調節及細胞在生觀點探討山藥生物活性之研究。國立陽明大學生物藥學研究所碩士論文。台北。
方銘志。2001。山藥多醣體之免疫機能探討。國立海洋大學食品科學所碩士論文。基隆。
黃仁彰。2000。菌種保存及研究簡訊。第四十二期。食品工業發展研究所。新竹。
鄭武燦。2000。台灣植物圖鑑。茂昌圖書有限公司發行。1482-1491。
王渭賢。1996。免疫促進物聚醣類在水生動物疾病防治之應用。生命科學簡訊。13(4):1619
松永政司。2001。水溶性核酸的免疫賦活機能以及利用。食品的開發。35(3):15-17
Abul KA., K.M., Sher A. et al .,. 1996. Functional diversity of helper T lymphocytes. Nature. 383:787-93.
Araghiniknam, M., Chung, S., Nelson-White, T. 1996. Antioxidant activity of dioscorea and dehydroepiandrosterone (DHEA) in older humans. Life Sci. 11:147-57.
Atuyuki Inoue, N.K., Nanba Hiroaki. 2002. Effect of maitake (Grifora frondosa) D-fraction on control of T lymph node Th-1/Th-2 proportion. Biol. Pharm. Bull. 25:536-540.
Beneytout, J.L., Nappez, C., Leboutet, M.J. and Malinvaud, G. 1995. A plantsteroid, diosgenin, a new megakaryocytic differentiation inducer of HEL cells. biochemical and biophysical research communication. Biochem. Biophys. Res. Commun. 207:398-404.
Bian, X., Jin, J., Ding, D., Zhang, H. 2002. Study on the scavenging action of polysaccharide of Usnea longissima to oxygen radical and its anti-lipi peroxidation effects. Chinese. 25:188-9.
Brunner, H.T., Mauel, J., Cerottini, J.C., Chapuis, B. 1968. Quantitative assay of the lytic action of immune lymphoid cells on 51Cr-labelled allogeneic target cells in vitro; inhibition by isoantibody and by drugs. Immunology. 14:181-196.
Campa-Cordova, A.I., Hernandez-Saavedra, N.Y., Ascencio, F. 2002. Superoxide dismutase as modulator of immune function in American white shrimp (Litopenaeus vannamei). Comp Biochem Physiol C Toxicol Pharmacol. 133:557-565.
Chen, H.M., Muramoto, K., Yamauchi, F., Nokihara, K. 1998. Antioxidative properties of histidine-containing peptides designed from peptide fragments found in the digests of a soybean protein. J. Agric. Food. Chem. 46:49-53.
Duell, P.B., Wheaton, L.D., Shultz A., Nguyen H.,. 1998. Inhibition of LDL oxidation by melatonin requires supraphysiologic concentrations. Clin Chem. 44:1931-6.
Ebina, T., Murata, K. 1992. Antitumor effect of PSK at a distant site: tumor-specific mmunity and combination with other chemotherapeutic agents. Jpn J Cancer Res. 83: 775-82.
Fukao, T., Yap, G., Gadina, M., O''Shea, J.J., Koyasu, S. 2001. Inducible expression of Stat4 in dendritic cells and macrophages and its critical role in innate and adaptive immune responses. J Immunol. 166:4446-4455.
Fukumoto, L., Mazza, G. 2000. Assessing antioxidant and prooxidant activities of phenolic compounds. J Agric Food Chem. 48:3597-604.
Halliwell, B. 1999. Food-derived antioxidants. evaluating their importance in food and in vivo. Food Science and Agricultural Chemistry. 1:67-109.
Halliwell, B., Gutteridge, J.M., Aruoma, O.I. 1987. The deoxyribose method: a simple "test-tube" assay for determination of rate constants for reactionsof hydroxyl radicals. Anal Biochem. 165:215-219.
Hamuro, J., Rollinghoff, M., Wagner, H. 1980. Induction of cytotoxic peritoneal exudate cells by T-cell immune adjuvants of the beta(1 leads to 3) glucan-type lentinan and its analogues. Immunology. 39:551-9.
Hanna, N., Burton, R.C., 1981. Definitive evidence that natural killer (NK) cells inhibit experimental tumor metastases in vivo. J Immunol. 127:1754-1758.
Hassid, W., et al. 1969. Biosynthesis of oligosaccharides andpolysaccharides in plants. Science. 165:137~4.
Hayakawa, K., et al. 1993. Effect of Krestin PSK) as adjuvant treatment on the prognosis after radical radiotherapy in patients with non-smallcell lung cancer. Anticancer Research. 13:1815-1820.
Hirai, R., Oguchi, Y., Sugita, N., Matsunaga, K., Nomoto, K. 1993. Enhancement of T-cell proliferation by PSK. In: Int J Immunopharmacol. 15:745-50.
Hirano, S., and Nagao, N. 1989. Effects of chitosan, pectic acid, lysozyme, and chitinase on the growth of several phytopathogens. Agric. Biol. Chem. 53:3065-3066.
Hotta, T., Yoshikumi, C., Ohara, M., Ueno, S.,. 1981. Protein-bound polysaccharides. US Patent. 4:151.
Hou, WC., H.F., Lee, M.H. 2002. Yam (Dioscorea batatas) tuber mucilage exhibited antioxidant activities in vitro. Planta Medica. 68:1072-6.
Hu, K., Dong, A., Yao, X., Kobayashi, H., and Iwasaki, S. 1996. Antineoplastic agents: three spirostanol glycosidesfrom rhizomes of Dioscorea collettii var. hypoglauca. Planta Med. 62:573-575.
Hu, K, Dong, A.J., Kobayashi, H., Iwasaki, S., Jing, Y.K. 1999. A new pregnane glycoside from dioscorea collettii var. hypoglauca. J Nat Prod. 62:299-301.
Ichikawa, Y., Takahashi, K., Yoshida, M., Moriuchi, J., Takaya, M., Arimori, S. 1989. Lymphocyte subsets of the peripheral blood in Sjogren''s syndrome and rheumatoid arthritis. Clin Exp Rheumatol7. 7:55-61.
Itoh, H., Amano, H., Zhuang, C. 1993. Antitumor activity andimmunological propertiesof marine algal polysaccharides, especially fucoidan, prepared from Sargassum thunbergiiof Phaeophyceae,. Anticancer Research. 13:2045-2052.
Iwu, M.M., Okunji, C.O., Ohiaeri, G.O., Akah, P., Corley, D., Tempesta, M.S. 1990. Hypoglycaemic activity of dioscoretine from tubers of dioscorea dumetorum in normal and alloxan diabetic rabbits. Planta Med. 56:264-267.
Jung M., Kang, S.S., Choi, J.H., Bae, K.S., Choi, J.S. 2003. Antioxidant activity from the stem bark of albizzia julibrissin. Archives of Pharmacal Research. 26:458-62,.
Kelmanson, J.E., Jäger, A.K., and van Staden, J. 2000. Zlul medical plants with antibacterial activity. J. Ethnopharm. 69:241-246.
Kikuchi, Y., Oomori, K., Iwano, I., Kita, T. 1988. Effects of PSK on interleukin-2 production by peripheral lymphocytes of patients with advancedovarian carcinoma during chemotherapy. Jpn J Cancer Res. 79:125-130.
Lee, J.M., Jeong, H., Lee, J.W., Lee, S.Y., Baek, S.J., Surh,Y.J. 2001. Inhibition of lipid peroxidation and oxidative DNA damage by Ganoderma lucidum. Phytother Res. 15:245-249.
Leh, Chang., Douglas, B.W., Chritton, Judith C.Folz, Lauralynn K. Lebeck and Sandra L. Nehlsen-Cannarella. 1993. Rapid flow cytometric assay for the assessment of natural killer cell activity. J Immunol Methods. 166:45-54.
Matsunaga, K., Nyunoya, Y., Hakozaki, M. 1994. Antitumor effect of biological response modifier, PSK, on C57BL/6 mice with syngeneic melanoma B16 and its mode of action. Oncology. 51:303-8.
Mei Zhou, Qian Quyang, Shang-Xi Liu, Zhan-Jun Pang. 2000b. Reduction of the oxidative injury to the rabbits with established atherosclerosis by protein bound polysaccharide from coriolus vesicolor. The American Journal of Chinese Medicine. 28:239-249.
Misaki, A., Ito, T., and Harada, T. 1972. Constitutional studieson themucilage of yamanoimo, Dioscorea batatas Decne, forma Tsukune. Isolation and structure ofa mannan. Agri. Biol. Chem. 51:2557-2561.
Mitomi, T., Iijima, N. 1992. A randomized controlled study on adjuvant immunochen=motherapy with PSK in curatively resected colorectal cancer. Proc Annu Meet Am Soc Clin Oncol. 11:A466.
Mori, T., Matsuura, M., Ueno, K., Tokura, S., Okamoto, Y., Fujinaga, T. 1997. Effect of chitin and its derivatives on the proliferation and cytokine production of fibroblasts in vitro. Biomaterials. 18:947?1.
Mosmann, T.R., Sad, S. 1996. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 17:138-146.
Nagafuchi, S., Nakagawa, E., Takahashi, T., Yajima, T., Yonekubo. 1997. Effects of dietary nucleotides on serum antibody and splenic cytokine production inmice. Nutr Res. 17:1163-1174.
Nakazato, H., Saji, S., Ogawa, N. 1994. Efficacy ofimmunochemotherapy as adjuvanttreatment after curative resection of gastric cancer. Study group of immunochemotherapy with PSK forgastric cancer. Lancet. 343:1122-1126.
Nicola, V., Tarugi, P. 1999. Influence of chondroitin sulfate charge density, sulfate group position, and molecular mass on Cu2+-mediated oxidation of human low-density lipoproteins: effect of normal human plasma-derived chondroitin sulfate. J Biochem (Tokyo). 125:297-304.
Nishikimi, M., Appaji Rao, N., Yagi, K. 1972. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecularoxygen. biochemical and biophysical research commuication. 46:849-54.
Noriko, K., Nachi, H., Hiroaki, N. 2002. A polysaccharide, extract from Grifola frondosa, induces Th-1 dominant responses in carcinoma-bearing BALB/c mice. Jpn. J. Pharmacol. 90:357-360.
Ozmeric, N., Haytac, C.M., Alaaddinoglu, E.E., Sargon, M.F., Senel, S. 2000. Chitosan film enriched with an antioxidant agent, taurine, in fenestration defects. J Biomed Mater Res. 51:500-503.
Pang, Z.J., Chen, Y., Wan, J. 1998. A protein-bound polysaccharide synergistic with lipopolysaccharide induces nitric oxide release and antioxidant enzyme activities in mouse peritoneal macrophages. The American Journal of Chinese Medicine. 26:133-141.
Pang, Z.J., Chen, Y., and Zhou, M. 2000. Polysaccharide krestin enhances manganese superoxide dismutase activity and mRNA expression in mouse peritoneal macrophages. The American Journal of Chinese Medicine. 28:331-341.
Petros, K., Kalogeris, E., Kekos, D., Macris, B.J., Christakopoulos, P. 2003. Enzymic production of a feruloylated oligosaccharide with antioxidant activity from wheat flour arabinoxylan. Eur J Nutr. 42:55-60.
Pilar. R., Ahrazem, O., Leal, J.A. 2002. Potential antioxidant capacity of sulfated polysaccharides from the edible marine brown seaweed Fucus vesiculosus. J Agric Food Chem. 50:840-845.
Piriou, L., Genetet, N., Albina, E. 2000. Design of a flow cytometric assay for the determination of natural killer and cytotoxic T-lymphocyte activity in human and in different animal species. Cytometry. 41:289-297.
Welsh, R.M. 1986. Regulation of virus infections by natural killer cells. Nat Immun Cell Growth Regul. 5:169-199.
Ross, G.D., Vetvicka, V., Yan, J., Xia, Y., and Vetvickova, J. 1999. Therapeutic intervention with complement and b-glucan in cancer. Immunopharmacology. 42:61-74.
Rosser, A. 1985. The day of the yam. Nursing Times. 81:47.
Sakagami, H., Kawazoe, Y. 1990. Novel elucidation of the mechanism of induction of various immunomodulating activities by a protein-bound polysaccharide, PSK. Anticancer Res. 10:1472.
Salin, M. 1988. Toxic oxygen species and protective systems of chloroplast.
Physiol. Plant. Physiol. Plant. 72:681-689.
Saran, M., Michel, C., Bors, W. 1998. Radical functions in vivo: a critical review of current concepts andhypotheses. Z Naturforsch. 53:210-27.
Shan, Y.Y., Kuroda, E., and Yamashita, A.U. 2000. Immunomodulating activity of seaweed extract on human lymphocytesin vitro. Int. J. Immunopharmacol. 21:59-70.
Shieh, D., Liu, L.T., Lin, C.C., 2000. Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin. Anticancer Res. 20 ::2861-5.
Sies, H. 1993. Strategies of antioxidant defense. Eur. J. Biochem. 215:213-219.
Sinclair, N.D. 1998. Chinese herbs: a clinical review of Astragalus, Ligusticum, and Schizandrae. Altern Med Rev. 3:338-44.
Slaga, T.J., A. J. P. Klein-Szanto, L. Triplett, I. P. Yotti and I. F.Tresko:. 1981. Skin tumor promotion activity of benzoylperoxide,widely used free radical generating compound. Science. 213:1023-1025
Sudo, N., Takaki, A., Tanaka, K., Yu, X.N., Oyama, N., Koga, Y., Kubo, C. 2000. Dietary nucleicacids promote a shift in Th1/Th2 balance toward Th1-dominant immunity. ... Clin Exp Allergy. 30:979-987.
Suzuki, I., Oikawa, S., Sato, K., Osawa, M. 1989. Antitumor and immunomodulating activities of a beta-glucan obtained from liquid-cultured Grifola frondosa. Chem Pharm Bull. 37:410-3.
Suzuki, K., et al. 1986a. A antitumor effects of hexa-N-acetyl-chitohexaose and chitohexaose. Carbohydr. Res. 151:403.
Suzuki, K., Tokoro, A., Okawa, Y., Suzuki, S., and Suzuki, M. 1986b. Effect ofN-acetyl-chitooligosaccharides on activation of phagocytes. Microbiol. Immunol. 30:777-787.
Taguchi,T. 1983. Effects of lentinan in advanced or recurrent cases of gastric,
colorectal, and breast cancer. Gan To Kagaku Ryoho. 10:387-393.
Takeshita,K.1991. Diversity of complement activation by lentinan, an antitumor polysaccharide, in gastric cancer patients. Nippon Geka Gakkai Zasshi. 92:5-11.
Tani, M., Amaue, H., Iwahashi, M., Isunoda, T., Tamai, M., Noguchi, K., Arii, K. 1992. In vitro generation of activated natural killer cells andcytotoxic macrophages with lentinan. Eur J Clin Pharmacol. 42:623-627.
Taro, P., Eorgo,Yap., et al.,. 1991. Induction of interleukin-1 production by ligandsbinding to the scavenger receptor in human monocytes and the THP-1 cell line. Immunology. 74::432-438.
Trinchieri, G. 1989. Biology of natural killer cells. Adv Immunol. 47:187-375.
Tsai shi-shun, T.F.-J. 1984. Studies on the mucilge from tuber of yam (Dioscorea alata Linn.). journal of the chinese agriculture chemistry society. 22:88~94.
Tsia, P.L., Huang, H.M. 2003. Free radical scavenging and antioxidative activity of melatonin derivatives. J Pharm Pharmacol. 55:1655-60.
Wagner, C., and Hänsch, G.M. 2004. Genetic deficiency of CD16, the low-affinity receptor for immunoglobulin G, has no impact on the functional capacity of polymorphonuclear neutrophils. European Journal of Clinical Investigation. 34:149-55.
Wakui, A., Konno, K., Abe, R., Kanamuru, R., Takahash, K., Nakai, Y., and Yoshida, Y., Madusa, H. et al. 1986. Randomized study of lentinan on patients with advanced gastric andcolorectal cancer. Jpn J Cancer Chemother. 13:1050-1059.
Wayner, D.D.M., Burton, G.W., Ingold, K.U., Barclay, L.R.C., Locke, S.J. 1987. The relative contribution of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma. Biochimica et Biophysica Acta. 924: 408-419.
Winterbourn, C.a.M., D.,. 1994. The reaction of superoxide withreduced glutathione. Arch Biochem Biophys. 314:284-290.
Xingfeng, B., Jinian, F. 2001. Structural features of an immunostimulating and antioxidant acidic polysaccharide from the seeds of Cuscuta chinensis. Planta Medica. 68:237-243.
Yamaguchi, T., Matoba, T., and Terao, J. 1998. Hplc method for evaluation of the free radical-scavenging activity of food by using 1,1-diphenyl-2-picrylhydarzyl. BioscienceBiotechnology Biochemistry. 62:1201-1204.
Yamamoto, I., Yagi, K., Tominaga, H., and Aoki, M. 1974. Antitumor effects of seaweeds. 1. antitumoreffects of extracts from sargassum and laminaria. Jpn J Exp Med. 44: 543-546.
Yan, L.J., D.-L.M., Packer, L.,. 1995. Ginkgo biloba eXtract ( EG B 761) protects human low density lipoproteins against oxidative modification mediated by copper. biochemical and biophysical research commuication. 212:360-366.
Yeh, S.L., Huey, F.S., Ming, T. L., Wei, J.C. 2004. Effects of glutamine supplementation on innate immune response in rats with gut-derived sepsis. British Journal of Nutrition. 91:423-429.
Yun, H., Hu, Q. 2003. Evaluation of antioxidant potential of aloe vera (Aloe barbadensis miller) extracts. J Agric Food Chem. 51:7788-7791.
Zhou, M., Chen, Y., Quyang, Q., Liu, S.X.., and Pang, Z.J. 2000. Reduction of the Oxidative Injury to the Rabbits with Established Atherosclerosis
by Protein Bound Polysaccharide from Coriolus Vesicolor. The American Journal of Chinese Medicine. 28:239-249.