臺灣博碩士論文加值系統

中文摘要
這項研究探討朝鮮薊薊花（WAF）和葉子（WAL）的水萃取物在突變和氧化損傷的抑制作用。結果顯示， WAF 和 WAL 的濃度範圍在1-10 mg/plate內在安氏試驗，抑制了Salmonella typhimurium TA 98和TA 100在間接型突變劑 (2-aminoanthracene, 2-AA) 和直接型的突變劑 (4-nitroquinoline-N-oxide, 4-NQO) 所引發的突變作用。另一方面， WAF和 WAL 在濃度50-200 µg/mL的範圍內表現出自由基清除活性、還原力活性、脂質體保護以及減少脂多醣體 (LPS) 在誘導巨噬細胞的氧化發炎毒性。高效能液相層析儀（HPLC）分析顯示，在 WAF 和 WAL 的活性分析中，酚類和類黃酮化合物被分析出洋薊酸 (cynarin) 、綠原酸 (chlorogenic acid) 和木犀草素-7-O-葡萄糖苷 (luteolin-7-O-glucoside) 。這些活性酚類及黃酮類成分可能有助於 WAF 和 WAL 在不同的模式下對生物分子的保護作用。這些結果顯示，WAF和WAL表現生物活性，可應用於抗突變以及抗氧化損傷。

Abstract
This study investigated the inhibitory effects of water extracts from Artichoke flowers (WAF) and leaves (WAL) on mutation and oxidative damage. The results showed that WAF and WAL in the range of 1–10 mg/plate inhibited the mutagenicity of 2-aminoanthracene (2-AA), an indirect mutagen, and 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen toward Salmonella typhimurium TA 98 and TA 100 in Ames test. On the other hand, WAF and WAL in the range of 50–200 µg/ml showed radical scavenging, reducing activities, liposome protection as 孔盤 as decreased lipopolysaccharides (LPS) induced inflammatory oxidative cytotoxicity in RAW264.7 cells. High performance liquid chromatography (HPLC) analysis suggested that the active phenolic and flavonoids constituents in WAF and WAL are cynarin, chlorogenic acid and luteolin-7-O-glucoside. These active phenolic and flavonoid components may contribute to the biological protection effects of WAF and WAL in different models. The data suggest that WAF and WAL exhibiting biological activities can be applied to antimutation as 孔盤 as anti-oxidative damage.

目錄
謝誌 I
摘要 II
Abstract III
目錄 IV
表目錄 X
圖目錄 XI
第一章 前言 1
一、 自由基 (Free radical) 與活性氧之介紹 1
(一)、 自由基與活性氧定義 1
(二)、 自由基的種類與來源 1
(三)、 自由基對人體的影響 3
二、 抗氧化物作用與種類 6
(一)、 抗氧化作用機制 6
(二)、 抗壞血酸 (Ascorbic acid) 6
(三)、 生育醇 (Tocopherol) 7
(四)、 酚類化合物 (Phenolic compounds) 7
(五)、 類黃酮化合物 (Flavonoid compounds) 8
三、 膳食與環境中的突變物質 9
(一)、 為何造成基因突變 9
(二)、 突變物質的來源與影響 11
(三)、 抗致基因突變機制 13
(四)、 基因突變檢驗測試—安氏試驗 (Ames test) 13
四、 發炎（Inflammation）與巨噬細胞（Macrophage） 16
(一)、 免疫系統（Immune system） 16
(二)、 自由基 (Free radical) 對發炎（Inflammation）的影響 17
(三)、 環氧合酶 (COX) 與發炎的關係 18
(四)、 誘導型一氧化氮合成酶 （iNOS） 與巨噬細胞 （Macrophage） 19
(五)、 NF-κB pathway 對炎症的重要性 20
五、 朝鮮薊 (Artichoke) 24
(一)、 朝鮮薊介紹 24
(二)、 朝鮮薊之保健功能 25
六、 研究動機與目的 26
第二章 材料與方法 27
一、 實驗樣品 27
二、 使用藥品與溶劑 27
三、 設備儀器 30
四、 樣品製備與實驗架構 33
(一)、 樣品處理 33
(二)、 實驗架構圖 33
五、 抗氧化含量測定試驗 34
(一)、 總多酚含量測定 34
(二)、 總黃酮含量測定 34
六、 抗氧化能力測定試驗 35
(一)、 DPPH自由基清除能力測定 35
(二)、 TEAC總抗氧化能力測定 35
(三)、 還原力能力測定 35
(四)、 脂質過氧化抑制能力測定 36
(五)、 酪胺酸酶活性抑制測定 37
七、 高效能液相層析 (HPLC) 分析 38
(一)、 內標準品配製 38
(二)、 指標成分溶液製備及檢量線製作 38
八、 安氏試驗 (Ames test) 41
(一)、 藥品製備 41
(二)、 挑選試驗菌株 44
(三)、 菌株保存方式 45
(四)、 主要培養皿 ( Master plate ) 45
(五)、 組胺酸需要性（Histidine requirement）測定 45
(六)、 rfa 突變（rfa mutation）測試 46
(七)、 R-因子 （R-factor）之測試 46
(八)、 uvrB 突變（uvrB mutation）之測試 46
(九)、 毒性試驗 47
(十)、 致突變試驗 ( Mutagenicity test ) 47
(十一)、 抗致突變試驗 ( Anti-mutagenicity test ) 48
九、 細胞培養及分析項目 49
(一)、 RAW264.7細胞株培養及處理 49
(二)、 細胞株保存方式 49
(三)、 RAW264.7細胞存活率試驗 49
(四)、 RAW264.7細胞一氧化氮 (NO) 生成量試驗 51
(五)、 西方墨點法 (Western blotting assay) - 分析iNOS, COX-2之表現量 52
第三章 結果與討論 56
一、 HPLC成分分析 56
二、 抗氧化成分定量 57
三、 抗氧化能力測定 57
四、 Ames test 59
(一)、 毒性試驗 59
(二)、 致突變試驗 59
(三)、 抗致突變試驗 60
五、 細胞試驗 63
(一)、 朝鮮薊水萃取物對RAW264.7細胞存活率之影響 63
(二)、 朝鮮薊水萃取物對RAW264.7細胞一氧化氮 (NO) 生成量之影響 63
(三)、 朝鮮薊水萃取物對RAW264.7細胞內 iNOS, COX-2 蛋白質表現量之影響 64
第四章 結論 65
參考文獻 67
附表 80
附圖 87


表目錄

表1、朝鮮薊花及葉子水萃取物之指標成分含量。 80
表2、朝鮮薊花及葉子水萃取物總黃酮及總多酚含量。 81
表3、朝鮮薊花及葉子水萃取物對 Salmonella typhimurium TA98 及TA100 之毒性試驗。 82
表4、朝鮮薊花及葉子水萃取物對 Salmonella typhimurium TA98 和TA100 之致突變試驗。 83
表5、朝鮮薊花及葉子水萃取物對Salmonella typhimurium TA98 和TA100 之抗致突變試驗。 84
表6、朝鮮薊花與葉子水萃取物對巨噬細胞 RAW 264.7的細胞存活率試驗 。 85
表7、朝鮮薊花與葉子水萃取物在脂多醣體 (LPS) 刺激巨噬細胞 RAW 264.7對一氧化氮 (NO) 的影響 86

圖目錄

圖1. 朝鮮薊花水萃取物指標成分HPLC 87
圖2. 朝鮮薊葉子水萃取物指標成分HPLC 88
圖3. 朝鮮薊花與葉子水萃取物之 DPPH 自由基清除能力測定 89
圖4. 朝鮮薊花與葉子水萃取物之 ABTS自由基清除能力測定 90
圖5. 朝鮮薊花與葉子水萃取物之還原力能力測定 91
圖6 朝鮮薊花與葉子水萃取物之脂質氧化抑制能力測定 92
圖7. 朝鮮薊花與葉子水萃取物之酪胺酸酶活性抑制能力測定 93
圖8. 朝鮮薊花與葉子水萃取物對 RAW264.7細胞在24小時 iNOS 及 COX-2蛋白質表現量之影響 94

參考文獻
1.Sies H. Strategies of antioxidant defense. Eur J Biochem. 1993; 215:213-219.
2.Zhang QA, Shen Y, Fan Xh, Martin JFG, Wang X, Song Y. Free radical generation induced by ultrasound in red wine and model wine: An EPR spin-trapping study. Ultrason Sonochem. 2015; 27:96-101.
3.Filipovic M, Markovic Z, Dorovic J, Markovic JD, Lucic B, Amic D. QSAR of the free radical scavenging potency of selected hydroxybenzoic acids and simple phenolics. C R Chim. 2015; 18:492-498.
4.Doonan R, McElwee JJ, Matthijssens F, et al. Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev. 2008; 22:3236-3241.
5.Atrous H, Benbettaieb N, Hosni F, et al. Effect of γ-radiation on free radicals formation, structural changes and functional properties of wheat starch. Int J Biol Macromol. 2015; 80:64-76.
6.Ramya R, Kalaiselvi M, Narmadha R, et al. Secondary metabolite credentials and in vitro free radical scavenging activity of Alpinia calcarata. JACME. 2015; 5:33-37.
7.Kim HS, Kim JA, Karadeniz F, Ahn BN, Kong CS. Radical scavenging and anti-inflammatory effects of the halophyte Spergularia marina Griseb. Z Naturforsch C. 2014; 69:425-433.
8.Shchepin R, Moller MN, Kim HH, et al. Tyrosine-Lipid Peroxide Adducts from Radical Termination: Para-Coupling and Intramolecular Diels-Alder Cyclization. J Am Chem Soc. 2010; 132:17490-17500.
9.Sikora A, Zielonka J, Lopez M, et al. Reaction between peroxynitrite and boronates: EPR spin-trapping, HPLC analyses, and quantum mechanical study of the free radical pathway. Chem Res Toxicol. 2011; 24:687-697.
10.Ghosh S, Derle A, Ahire M, et al. Phytochemical Analysis and Free Radical Scavenging Activity of Medicinal Plants Gnidia glauca and Dioscorea bulbifera. PLoS One. 2013; 8:82529.
11.Liang SS, Shiue YL, Kuo CJ, Guo SE, Liao WT, Tsai EM. Online Monitoring Oxidative Products and Metabolites of Nicotine by Free Radicals Generation with Fenton Reaction in Tandem Mass Spectrometry. Int J Mol Sci. 2013; 15:20770-20788.
12.Gomez Mejiba SE, Zhai Z, Akram H, et al. Immuno-spin trapping of protein and DNA radicals: “tagging” free radicals to locate and understand the redox process. Free Radic Biol Med. 2009; 46:853-865.
13.Valavanidis A, Vlachogianni T, Fiotakis K. Tobacco Smoke: Involvement of Reactive Oxygen Species and Stable Free Radicals in Mechanisms of Oxidative Damage, Carcinogenesis and Synergistic Effects with Other Respirable Particles. Int J Environ Res Public Health. 2009; 6:445-462.
14.Ramirez DC, Gomez Mejiba SE, Corbett JT, Deterding LJ, Tomer KB, Mason RP. Cu, Zn-Superoxide Dismutase-driven Free Radical Modifications: Copper- and Carbonate Radical Anion-initiated Protein Radical Chemistry. Biochem J. 2009; 417:341-353.
15.Cadet J, Wagner JR, Shafirovich V, Geacintov NE. One-electron oxidation reactions of purine and pyrimidine bases in cellular DNA. Int J Radiat Biol. 2014; 90:423-432.
16.Crean C, Geacintov NE, Shafirovich V. Intrastrand G-U cross-links generated by the oxidation of guanine in 5'-d(GCU) and 5'-r(GCU). Free Radic Biol Med. 2008; 45:1125-1134.
17.Bhattacharjee S, Chatterjee S, Jiang JJ, Sinha BK, Mason RP. Detection and imaging of the free radical DNA in cells—Site-specific radical formation induced by Fenton chemistry and its repair in cellular DNA as seen by electron spin resonance, immuno-spin trapping and confocal microscopy. Nucleic Acids Res. 2012; 40:5477-5486.
18.Kidane D, Chae WJ, Czochor J, et al. Interplay between DNA repair and inflammation, and the link to cancer. Crit Rev Biochem Mol Biol. 2014; 49:116-139.
19.Borodkina A, Shatrova A, Abushik P, Nikolsky N, Burova E. Interaction between ROS dependent DNA damage, mitochondria and p38 MAPK underlies senescence of human adult stem cells. Aging (Albany NY). 2014; 6:481-495.
20.Poljsak B, Fink R. The Protective Role of Antioxidants in the Defence against ROS/RNS-Mediated Environmental Pollution. Oxid Med Cell Longev. 2014;20:1467-1539
21.Leopold JA, Loscalzo J. Oxidative Risk for Atherothrombotic Cardiovascular Disease. Free Radic Biol Med. 2009; 47:1673-1706.
22.Sung CC, Hsu YC, Chen CC, Lin YF, Wu CC. Oxidative Stress and Nucleic Acid Oxidation in Patients with Chronic Kidney Disease. Oxid Med Cell Longev. 2013; 20:1330-1982
23.Fillmore N, Mori J, Lopaschuk GD. Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy. Br J Pharmacol. 2014; 171:2080-2090.
24.Rahal A, Kumar A, Singh V, et al. Oxidative Stress, Prooxidants, and Antioxidants: The Interplay. Biomed Res Int. 2014; 2014: 761264.
25.Hercberg S, Galan P, Preziosi P, Alfarez MJ, Vazquez C. The potential role of antioxidant vitamins in preventing cardiovascular diseases and cancers. Nutrition. 1998; 14:513-520.
26.Wambi C, Sanzari J, Wan XS, et al. Dietary Antioxidants Protect Hematopoietic Cells and Improve Animal Survival after Total-Body Irradiation. Radiat Res. 2008; 169:384-396.
27.Chalamaiah M, Dinesh kumar B, Hemalatha R, Jyothirmayi T. Fish protein hydrolysates: Proximate composition, amino acid composition, antioxidant activities and applications: A review. Food Chemistry. 2012; 135:3020-3038.
28.Raseetha S, Leong SY, Burritt DJ, Oey I. Understanding the degradation of ascorbic acid and glutathione in relation to the levels of oxidative stress biomarkers in broccoli (Brassica oleracea L. italica cv. Bellstar) during storage and mechanical processing. Food Chemistry. 2013; 138:1360-1369.
29.Yen GC, Wu JY. Antioxidant and radical scavenging properties of extracts from Ganoderma tsugae. Food Chemistry. 1999; 65:375-379.
30.Yao X, Zhu L, Chen Y, Tian J, Wang Y. In vivo and in vitro antioxidant activity and α-glucosidase, α-amylase inhibitory effects of flavonoids from Cichorium glandulosum seeds. Food Chemistry. 2013; 139:59-66.
31.Michotte D, Rogez H, Chirinos R, Mignolet E, Campos D, Larondelle Y. Linseed oil stabilisation with pure natural phenolic compounds. Food Chemistry. 2011; 129:1228-1231.
32.Chang YZ, Lin HC, Chan ST, Yeh SL. Effects of quercetin metabolites on the enhancing effect of β-carotene on DNA damage and cytochrome P1A1/2 expression in benzo[a]pyrene-exposed A549 cells. Food Chemistry. 2012; 133:445-450.
33.Hidalgo M, Sanchez Moreno C, de Pascual Teresa S. Flavonoid–flavonoid interaction and its effect on their antioxidant activity. Food Chemistry. 2010; 121:691-696.
34.Guo W, Wei X, Wu S, et al. Antagonistic effect of flavonoids on NSC-741909-mediated antitumor activity via scavenging of reactive oxygen species. Eur J Pharmacol. 2010; 649:51-58.
35.Erickson RP. Somatic gene mutation and human disease other than cancer: An update. Mutat Res Rev Mutat Res. 2010; 705:96-106.
36.Donko A, Morand S, Korzeniowska A, et al. Hypothyroidism-associated missense mutation impairs NADPH oxidase activity and intracellular trafficking of Duox2. Free Radic Biol Med. 2014; 73:190-200.
37.Weyemi U, Dupuy C. The emerging role of ROS-generating NADPH oxidase NOX4 in DNA-damage responses. Mutat Res Rev Mutat Res. 2012; 751:77-81.
38.An G, Kulkarni S. An agent-based modeling framework linking inflammation and cancer using evolutionary principles: Description of a generative hierarchy for the hallmarks of cancer and developing a bridge between mechanism and epidemiological data. Math Biosci. 2015; 260:16-24.
39.Baena Ruiz R, Salinas Hernandez P. Diet and cancer: Risk factors and epidemiological evidence. Maturitas. 2014; 77:202-208.
40.Tedesco I, Russo M, Russo P, et al. Antioxidant effect of red wine polyphenols on red blood cells. J Nutr Biochem. 2000;11:114-119.
41.Wu Y, Antony S, Meitzler JL, Doroshow JH. Molecular mechanisms underlying chronic inflammation-associated cancers. Cancer Letters. 2014; 345:164-173.
42.Kanamura S, Watanabe J Cell biology of cytochrome P-450 in the liver. In: Kwang WJ, ed. Int Rev Cytol. 2000;198:109-52.
43.Oleary KA, Beck TW, Kasper CB. NADPH Cytochrome P-450 Oxidoreductase Gene: Identification and Characterization of the Promoter Region. Arch Biochem Biophys. 1994; 310:452-459.
44.Truan G, Epinat JC, Rougeulle C, Cullin C, Pompon D. Cloning and characterization of a yeast cytochrome b5-encoding gene which suppresses ketoconazole hypersensitivity in a NADPH-P-450 reductase-deficient strain. Gene. 1994; 142:123-127.
45.Fahrig R. Metabolic activation of aryldialkyltriazenes in the mouse: induction of mitotic gene conversion in Saccharomyces cerevisiae in the host-mediated assay. Mutat Res. 1971; 13:436-439.
46.Schober W, Pusch G, Oeder S, Reindl H, Behrendt H, Buters JTM. Metabolic activation of phenanthrene by human and mouse cytochromes P450 and pharmacokinetics in CYP1A2 knockout mice. Chem Biol Interact. 2010; 183:57-66.
47.Sumida K, Ooe N, Nagahori H, et al. An in Vitro Reporter Gene Assay Method Incorporating Metabolic Activation with Human and Rat S9 or Liver Microsomes. Biochem Biophys Res Commun. 2001; 280:85-91.
48.Wang G, Humayun MZ, Taylor DE. Mutation as an origin of genetic variability in Helicobacter pylori. Trends Microbiol. 1999; 7:488-493.
49.Wakabayashi K, Sugimura T. Heterocyclic amines formed in the diet: carcinogenicity and its modulation by dietary factors. J Nutr Biochem. 1998; 9:604-612.
50.Koide N, Ito H, Mu MM, et al. Inhibition of extracellular signal-regulated kinase 1/2 augments nitric oxide production in lipopolysaccharide-stimulated RAW264.7 macrophage cells. FEMS Immunol Med Microbiol. 2005; 45:213-219.
51.Lee SA, Kim EY, Jeon WK, et al. The inhibitory effect of raloxifene on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells is mediated through a ROS/p38 MAPK/CREB pathway to the up-regulation of heme oxygenase-1 independent of estrogen receptor. Biochimie. 2011; 93:168-174.
52.Mohan IK, Das UN. Effect of l-arginine–nitric oxide system on chemical-induced diabetes mellitus. Free Radic Biol Med. 1998; 25:757-765.
53.Ohshima H, Yoshie Y, Auriol S, Gilibert I. Antioxidant and pro-oxidant actions of flavonoids: effects on DNA damage induced by nitric oxide, peroxynitrite and nitroxyl anion. Free Radic Biol Med. 1998; 25:1057-1065.
54.Wolfle U, Esser PR, Simon-Haarhaus B, Martin SF, Lademann J, Schempp CM. UVB-induced DNA damage, generation of reactive oxygen species, and inflammation are effectively attenuated by the flavonoid luteolin in vitro and in vivo. Free Radic Biol Med. 2011; 50:1081-1093.
55.Anderson D. Antioxidant defences against reactive oxygen species causing genetic and other damage. Mutat Res Rev Mutat Res. 1996; 350:103-108.
56.Halliwell B. Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutat Res Genet Toxicol Environ Mutagen. 1999; 443:37-52.
57.Weisburger JH. Actual carcinogens and promoters involved in colon cancer causation and development. Nutrition. 2000; 16:164.
58.Porta M, Crous Bou M, Wark PA, et al. Cigarette smoking and K-ras mutations in pancreas, lung and colorectal adenocarcinomas: Etiopathogenic similarities, differences and paradoxes. Mutat Res Rev Mutat Res. 2009; 682:83-93.
59.Song MK, Park YK, Ryu JC. Polycyclic aromatic hydrocarbon (PAH)-mediated upregulation of hepatic microRNA-181 family promotes cancer cell migration by targeting MAPK phosphatase-5, regulating the activation of p38 MAPK. Toxicol Appl Pharmacol. 2013; 273:130-139.
60.Yu XJ, Yang MJ, Zhou B, et al. Characterization of Somatic Mutations in Air Pollution-Related Lung Cancer. EBioMedicine. 2015; 2:583-590.
61.Ramel C, Alekperov UK, Ames BN, Kada T, Wattenberg LW. Inhibitors of mutagenesis and their relevance to carcinogenesis: Report by ICPEMC expert group on antimutagens and desmutagens. Mutat Res Genet Toxicol Environ Mutagen. 1986; 168:47-65.
62.David Josephy P, Gruz P, Nohmi T. Recent advances in the construction of bacterial genotoxicity assays. Mutat Res Rev Mutat Res. 1997; 386:1-23.
63.Kim BS, Margolin BH. Statistical methods for the Ames Salmonella assay: a review. Mutat Res Rev Mutat Res. 1999; 436:113-122.
64.De Raat WK, Willems MI, de Meijere FA. Effects of amount and type of agar on the number of spontaneous revertants in the Ames test. Mutat Res Genet Toxicol Environ Mutagen. 1984; 137:33-37.
65.Baggiolini M, Loetscher P. Chemokines in inflammation and immunity. Immunol Today. 2000; 21:418-420.
66.Y Ando I, Tsukumo Y, Wakabayashi T, et al. Safflower polysaccharides activate the transcription factor NF-κB via Toll-like receptor 4 and induce cytokine production by macrophages. Int Immunopharmacol. 2002; 2:1155-1162.
67.Brown AJ, Mander EL, Gelissen IC, Kritharides L, Dean RT, Jessup W. Accumulation of oxidised esters in lysosomes of macrophage foam cells. J Lipid Res. 2000; 151:291.
68.Mander EL, Dean RT, Stanley KK, Jessup W. Apolipoprotein B of oxidized LDL accumulates in the lysosomes of macrophages. Biochim Biophys Acta. 1994; 1212:80-92.
69.Linda R. Watkins , Steven F. Maier , Lisa E. Goehler. Oxygen Free Radicals, Nitric Oxide and Cytokines in Inflammation. Free Radical Biology and Medicine. 2004; 36, 39-40.
70.Goldstein IM, Perez HD, Weksler BB. Oxygen-derived free radicals and inflammation: Role of arachidonic acid. Semin Arthritis Rheum. 1981; 11:99-101.
71.Newman A. Free Radical Biology & Medicine: The last 20 years: The most highly cited papers. Free Radic Biol Med. 2005; 39:1265-1290.
72.Arias JI, Aller MA, Sanchez Patan F, Arias J. Inflammation and cancer: Is trophism the link? Surg Oncol. 2006; 15:235-242.
73.Onuma K, Suenaga Y, Sakaki R, et al. Development of a quantitative bioassay to assess preventive compounds against inflammation-based carcinogenesis. Nitric Oxide. 2011; 25:183-194.
74.Chen H, Ma F, Hu X, Jin T, Xiong C, Teng X. Elevated COX2 expression and PGE2 production by downregulation of RXRα in senescent macrophages. Biochem Biophys Res Commun. 2013; 440:157-162.
75.Lau FC, Joseph JA, McDonald JE, Kalt W. Attenuation of iNOS and COX2 by blueberry polyphenols is mediated through the suppression of NF-κB activation. J Funct Foods. 2009; 1:274-283.
76.McNeill E, Crabtree MJ, Sahgal N, et al. Regulation of iNOS function and cellular redox state by macrophage Gch1 reveals specific requirements for tetrahydrobiopterin in NRF2 activation. Free Radic Biol Med. 2015; 79:206-216.
77.Yang YZ, Tang YZ, Liu YH. Wogonoside displays anti-inflammatory effects through modulating inflammatory mediator expression using RAW264.7 cells. J Ethnopharmacol. 2013; 148:271-276.
78.El Achkar GA, Jouni M, Mrad MF, et al. Thiazole derivatives as inhibitors of cyclooxygenases in vitro and in vivo. Eur J Pharmacol. 2015; 750:66-73.
79.Huang WC, Tsai PJ, Huang YL, Chen SN, Chuang LT. PGE2 production is suppressed by chemically-synthesized 7-eicosatrienoic acid in macrophages through the competitive inhibition of COX-2. Food Chem Toxicol. 2014; 66:122-133.
80.Xiong H, Cheng Y, Zhang X, Zhang X. Effects of taraxasterol on iNOS and COX-2 expression in LPS-induced RAW 264.7 macrophages. J Ethnopharmacol. 2014; 155:753-757.
81.Yang LM, Chang SF, Lin WK, et al. Oxygenated compounds from the bioconversion of isostevic acid and their inhibition of TNF-α and COX-2 expressions in LPS-stimulated RAW 264.7 cells. Phytochemistry. 2012; 75:90-98.
82.Dai Y, Zhang X, Peng Y, Wang Z. The expression of cyclooxygenase-2, VEGF and PGs in CIN and cervical carcinoma. Gynecol Oncol. 2005; 97:96-103.
83.Jung KH, Ha E, Kim MJ, et al. Suppressive effects of nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by Citrus reticulata extract in RAW 264.7 macrophage cells. Food Chem Toxicol. 2007; 45:1545-1550.
84.Berka V, Liu W, Wu G, Tsai AL. Comparison of oxygen-induced radical intermediates in iNOS oxygenase domain with those from nNOS and eNOS. J Inorg Biochem. 2014; 139:93-105.
85.Kim AR, Lee MS, Shin TS, et al. Phlorofucofuroeckol A inhibits the LPS-stimulated iNOS and COX-2 expressions in macrophages via inhibition of NF-κB, Akt, and p38 MAPK. Toxicology in Vitro. 2011; 25:1789-1795.
86.Su YW, Chiou WF, Chao SH, Lee MH, Chen CC, Tsai YC. Ligustilide prevents LPS-induced iNOS expression in RAW 264.7 macrophages by preventing ROS production and down-regulating the MAPK, NF-κB and AP-1 signaling pathways. Int Immunopharmacol. 2011; 11:1166-1172.
87.Koppula S, Kumar H, Kim IS, Choi DK. Reactive Oxygen Species and Inhibitors of Inflammatory Enzymes, NADPH Oxidase, and iNOS in Experimental Models of Parkinson's Disease. Mediators Inflamm. 2012; 2012:823902.
88.Bast A, Erttmann SF, Walther R, Steinmetz I. Influence of iNOS and COX on peroxiredoxin gene expression in primary macrophages. Free Radic Biol Med. 2010; 49:1881-1891.
89.Park SG, Lee T, Kang HY, Park K, Cho KH, Jung G. The influence of the signal dynamics of activated form of IKK on NF-κB and anti-apoptotic gene expressions: A systems biology approach. FEBS Letters. 2006; 580:822-830.
90.Picard C, Puel A, Bustamante J, et al. 36 - Inherited disorders of IFN-γ-, IFN-α/β/λ-, and NF-κB-mediated immunity. In: Weyand RRRAFTSWSJFM, ed. Clinical Immunology (Fourth Edition). 2013: 454-464.
91.De Martin R, Schmid JA, Hofer Warbinek R. The NF-κB/Rel family of transcription factors in oncogenic transformation and apoptosis. Mutat Res Rev Mutat Res. 1999; 437:231-243.
92.Leung TH, Hoffmann A, Baltimore D. One Nucleotide in a κB Site Can Determine Cofactor Specificity for NF-κB Dimers. Cell. 2004; 118: 453-464.
93.Wang Vivien YF, Huang W, Asagiri M, et al. The Transcriptional Specificity of NF-κB Dimers Is Coded within the κB DNA Response Elements. Cell Reports. 2012; 2:824-839.
94.Erstad DJ, Cusack Jr JC. Targeting the NF-κB Pathway in Cancer Therapy. Surg Oncol Clin N Am. 2013; 22:705-746.
95.Sethi G, Tergaonkar V. Potential pharmacological control of the NF-κB pathway. Trends Pharmacol Sci. 2009; 30:313-321.
96.Fu H. Subunit interaction maps for the regulatory particle of the 26S proteasome and the COP9 signalosome. EMBO J. 2001; 20:7096-7107.
97.Magne N, Toillon RA, Bottero V, et al. NF-κB modulation and ionizing radiation: mechanisms and future directions for cancer treatment. Cancer Letters. 2006; 231:158-168.
98.Sfikas A, Batsi C, Tselikou E, et al. The canonical NF-κB pathway differentially protects normal and human tumor cells from ROS-induced DNA damage. Cellular Signalling. 2012; 24:2007-2023.
99.Castrillo A, Pennington DJ, Otto F, Parker PJ, Owen MJ, Bosca L. Protein Kinase: Is Required for Macrophage Activation and Defense Against Bacterial Infection. J Exp Med. 2001; 194:1231-1242.
100.Vella L, Markworth JF, Peake JM, Snow RJ, Cameron‐Smith D, Russell AP. Ibuprofen supplementation and its effects on NF‐κB activation in skeletal muscle following resistance exercise. Physiol Rep. 2014; 2:12172.
101.Li Q, Withoff S, Verma IM. Inflammation-associated cancer: NF-κB is the lynchpin. Trends Immunol. 2005; 26:318-325.
102.Banner KH, De Jonge H, Elborn S, et al. Highlights of a workshop to discuss targeting inflammation in cystic fibrosis. J Cyst Fibros. 2009; 8:1-8.
103.Piscioneri I, Sharma N, Baviello G, Orlandini S. Promising industrial energy crop, Cynara cardunculus: a potential source for biomass production and alternative energy. Energy Convers Manage. 2000; 41:1091-1105.
104.Baker RG, Hayden MS, Ghosh S. NF-κB, Inflammation, and Metabolic Disease. Cell Metabolism. 2011; 13:11-22.
105.Yang L, He QS, Corscadden K, Udenigwe CC. The prospects of Jerusalem artichoke in functional food ingredients and bioenergy production. Biotechnology Reports. 2015; 5:77-88.
106.Saenz Rodriguez T, Garcia Gimenez D, de la Puerta Vazquez R. Choleretic activity and biliary elimination of lipids and bile acids induced by an artichoke leaf extract in rats. Phytomedicine. 2002; 9:687-693.
107.Raccuia SA, Melilli MG. Seasonal dynamics of biomass, inulin, and water-soluble sugars in roots of Cynara cardunculus L. Field Crops Research. 2010; 116:147-153.
108.Lattanzio V, Kroon PA, Linsalata V, Cardinali A. Globe artichoke: A functional food and source of nutraceutical ingredients. J Funct Foods. 2009; 1:131-144.
109.Ogasa T, Arawo Y. Studies on Jerusalem Artichoke (Helianthus tuberosus L.), I. Process of the Growth and Tuberization and Changes in the Content of Main Constituents. Jpn J Crop Sci. 1940; 12:31-40.
110.Chen F, Long X, Yu M, Liu Z, Liu L, Shao H. Phenolics and antifungal activities analysis in industrial crop Jerusalem artichoke (Helianthus tuberosus L.) leaves. Ind Crops Prod. 2013; 47:339-345.
111.Li L, Wu LL. Chapter Fourteen - Adiponectin and Interleukin-6 in Inflammation-Associated Disease. In: Gerald L, ed. Vitamins & Hormones. 2012; 90:375-395.
112.Gupta S, Gambhir JK, Kalra OP, et al. Association of biomarkers of inflammation and oxidative stress with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population. J Diabetes Complications. 2013; 27:548-552.
113.Yuan X, Gao M, Xiao H, Tan C, Du Y. Free radical scavenging activities and bioactive substances of Jerusalem artichoke (Helianthus tuberosus L.) leaves. Food Chemistry. 2012; 133:10-14.
114.Pereira C, Calhelha RC, Barros L, Queiroz MJRP, Ferreira ICFR. Synergisms in antioxidant and anti-hepatocellular carcinoma activities of artichoke, milk thistle and borututu syrups. Ind Crops Prod. 2014; 52:709-713.
115.Pereira C, Calhelha RC, Barros L, Ferreira ICFR. Antioxidant properties, anti-hepatocellular carcinoma activity and hepatotoxicity of artichoke, milk thistle and borututu. I Ind Crops Prod. 2013; 49:61-65.
116.Trouillas P, Calliste CA, Allais DP, et al. Antioxidant, anti-inflammatory and antiproliferative properties of sixteen water plant extracts used in the Limousin countryside as herbal teas. Food Chemistry. 2003; 80:399-407.
117.Amoateng P, Assumeng Koffuor G, Sarpong K, Oteng Agyapong K. Free Radical Scavenging and Anti-lipid Peroxidative Effects of a Hydro-ethanolic Extract of the Whole Plant of Synedrella nodiflora (L.) Gaertn (Asteraceae). Free Radicals and Antioxidants. 2011; 1:70-78.
118.Hossain MA, Kalbani MSAA, Farsi SAJA, Weli AM, Al Riyami Q. Comparative study of total phenolics, flavonoids contents and evaluation of antioxidant and antimicrobial activities of different polarities fruits crude extracts of Datura metel L. Asian Pacific Journal of Tropical Disease. 2014; 4:378-383.
119.Riesz P, Kondo T. Free radical formation induced by ultrasound and its biological implications. Free Radic Biol Med. 1992; 13:247-270.
120.Rice Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med. 1996; 20:933-956.
121.Kumar V, Rani A, Dixit AK, Pratap D, Bhatnagar D. A comparative assessment of total phenolic content, ferric reducing-anti-oxidative power, free radical-scavenging activity, vitamin C and isoflavones content in soybean with varying seed coat colour. Food Research International. 2010; 43:323-328.
122.Dmitriev LF, Ivanova MV, Lankin VZ. Interaction of tocopherol with peroxyl radicals does not lead to the formation of lipid hydroperoxides in liposomes. Chem Phys Lipids. 1994; 69:35-39.
123.Hunter EPL, Desrosiers MF, Simic MG. The effect of oxygen, antioxidants, and superoxide radical on tyrosine phenoxyl radical dimerization. Free Radic Biol Med. 1989; 6:581-585.
124.Stevens MG, Olsen SC. Comparative analysis of using MTT and XTT in colorimetric assays for quantitating bovine neutrophil bactericidal activity. J Immunol Methods. 1993; 157:225-231.
125.Bryan NS, Calvert JW, Gundewar S, Lefer DJ. Dietary nitrite restores NO homeostasis and is cardioprotective in endothelial nitric oxide synthase-deficient mice. Free Radic Biol Med. 2008; 45:468-474.
126.Amano F, Noda T. Improved detection of nitric oxide radical (NO•) production in an activated macrophage culture with a radical scavenger, cary PTIO, and Griess reagent. FEBS Letters. 1995; 368:425-428.
127.Cummings PJ. Simulated western blot for the science curriculum. Biochemical Education. 1997; 25:39-40.
128.Kido T, Yook HY, Ueda K. Ligand western blotting for specific detection of active forms of proteases. Clinica Chimica Acta. 1995; 237:31-41.
129.Kirchhoff R, Beckers CH, Kirchhoff GM, Trinczek Gartner H, Petrowicz O, Reimann HJ. Increase in choleresis by means of artichoke extract. Phytomedicine. 1994; 1:107-115.
130.Hammerschmidt R. Chlorogenic acid: A versatile defense compound. Physiol Mol Plant Pathol. 2014; 88:3-4.
131.Morishita H, Ohnishi M. Absorption, metabolism and biological activities of chlorogenic acids and related compounds. In: Atta ur R, ed. Free Radic Biol Med. 2001; 25:919-953.
132.Albayrak S, Aksoy A, Sagdic O, Hamzaoglu E. Compositions, antioxidant and antimicrobial activities of Helichrysum (Asteraceae) species collected from Turkey. Food Chemistry. 2010; 119:114-122.
133.Jung HA, Jin SE, Min BS, Kim BW, Choi JS. Anti-inflammatory activity of Korean thistle Cirsium maackii and its major flavonoid, luteolin 5-O-glucoside. Food Chem Toxicol. 2012; 50:2171-2179.
134.Turkyılmaz M, Tagı S, Dereli U, Ozkan M. Effects of various pressing programs and yields on the antioxidant activity, antimicrobial activity, phenolic content and colour of pomegranate juices. Food Chemistry. 2013; 138:1810-1818.
135.Floegel A, Kim DO, Chung SJ, Koo SI, Chun OK. Comparison of ABTS/DPPH assays to measure antioxidant capacity in popular antioxidant-rich US foods. J Food Compost Anal. 2011; 24:1043-1048.
136.Gliszczynska Swigło A. Antioxidant activity of water soluble vitamins in the TEAC (trolox equivalent antioxidant capacity) and the FRAP (ferric reducing antioxidant power) assays. Food Chemistry. 2006; 96:131-136.
137.Odabasoglu F, Aslan A, Cakir A, et al. Antioxidant activity, reducing power and total phenolic content of some lichen species. Fitoterapia. 2005; 76:216-219.
138.Bajpai VK, Sharma A, Kang SC, Baek KH. Antioxidant, lipid peroxidation inhibition and free radical scavenging efficacy of a diterpenoid compound sugiol isolated from Metasequoia glyptostroboides. Asian Pac J Trop Med. 2014; 7:9-15.
139.Saini AS, Kumar J, Melo JS. Microplate based optical biosensor for l-Dopa using tyrosinase from Amorphophallus campanulatus. Anal Chim Acta. 2014; 849:50-56.
140.Venitt S. The use of short-term tests for the detection of genotoxic activity in body fluids and excreta. Mutat Res Genet Toxicol Environ Mutagen. 1988; 205:331-353.
141.Franke SIR, Ckless K, Silveira JD, et al. Study of antioxidant and mutagenic activity of different orange juices. Food Chemistry. 2004; 88:45-55.
142.Sarac N, Sen B. Antioxidant, mutagenic, antimutagenic activities, and phenolic compounds of Liquidambar orientalis Mill. var. orientalis. Ind Crops Prod. 2014; 53:60-64.
143.Yang HL, Chen SC, Lin KY, et al. Antioxidant activities of aqueous leaf extracts of Toona sinensis on free radical-induced endothelial cell damage. J Ethnopharmacol. 2011; 137:669-680.