臺灣博碩士論文加值系統

慢性發炎(Chronic inflammation)為造成許多慢性疾病的主要原因，已知許多中草藥可藉由其具有抗氧化和抗發炎活性的二次代謝物來改善由發炎所造成的慢性疾病。中國橄欖為常見之中藥材及食材，具有優良的抗氧化及肝保護之作用，本研究室過往的研究指出中國橄欖的甲醇萃取物之乙酸乙酯區分層具有很好的抗發炎效果。本次研究目的是以細胞平台為導向，利用不同的化學分離方式，篩選出具有抗發炎效果的活性物質。本研究所使用之生物平台係以本實驗室已建構於RAW 264.7 細胞中可以偵測NF-κB活性及COX-2表現量的兩種與發炎相關之冷光報導基因平台，利用極性沉澱之溶解度分離，發現上清液層具有較好的抗發炎效果，將上清液層以矽膠管柱分離提升次區分層抗發炎效果，顯示在D次區分層具有抗發炎效果，但卻同時伴隨著細胞毒性。將D次區分層再以矽膠管柱分離，發現D-11次區分層具有較佳的抗發炎效果，但同樣也伴隨著細胞毒性，且具有劑量效應，將D-11次區分層以薄層層析(Thin layer chromatography)大量收集具有螢光之條帶，並再以LH-20純化後以核磁共振(nuclear magnetic resonance )鑑定成分，發現主要成分應為Scoparone，HPLC定量結果顯示Scoparone含量的確會隨分離純化層數增加而增加。以發炎平台驗證Scoparone的抗發炎功效，卻發現Scoparone無法抑制由LPS誘導的發炎反應。以回添試驗探討Scoparone與萃取基質的協同作用，結果仍是無提升抗發炎效果，而在單以LPS誘導的發炎模式下，Scoparone對於一氧化氮生成的抑制效果較文獻中以INF-γ/LPS誘導發炎的抑制效果弱，代表Scoparone並非中國橄欖甲醇萃取乙酸乙酯區分層抗發炎功效的主要成分，必須分離純化在D-11次區分層中的其他次要成分方可找出其抗發炎的主要成分。

Chronic inflammation is one of the factors causing chronic disorders. Many secondary metabolites extracted from herbs exhibit both anti-oxidative and anti-inflammatory activities, and may have potential against inflammation-induced chronic diseases.

Canarium album is a common herb and food with excellent anti-oxidative and hepatoprotective effects. Its ethyl acetate fraction from methanol extract has been proved to exhibit good anti-inflammatory potential in our previous work.The objective of this research is to use different isolation techniques to screen bioactive fractions guided by bioassays to obtain anti-inflammatory compounds. The bioassay is a luciferase reporter assay built by our lab using the cell line RAW 264.7 that has been constructed with either NF-κB binding site or COX-2 promoter. First, the fraction was separated based on polarity differences, and the supernatant was found to have better anti-inflammatory action than the precipitate. It was then isolated with silica gel chromatography, and the anti-inflammatory action was concentrated in sub-fraction D, which also showed substantial cytotoxicity. When sub-fraction D was subjected to isolation again with silica gel chromatography, sub-fraction D-11 was found to have better anti-inflammatory action, but also with dose-dependent cytotoxicity.After isolation and purification by thin-layer chromatography and LH-20 column, the active compound from sub-fraction D-11 was identified to be scoparone by nuclear magnetic resonance. Quantification by HPLC showed that scoparone increases as purification steps increase. However, scoparone was unable to inhibit LPS-induced inflammation in the luciferase reporter assay. When spiking scoparone into the extract to explore whether there is synergy between the two, the result was negative. Furthermore, scoparone exhibited a weaker effect of inhibiting NO-induced inflammation than INF-γ/LPS-induced inflammation in literature, indicating scoparone was not the active anti-inflammatory factor in ethyl acetate fraction of methanol extract of C. album. Identification of other components in sub-fraction D-11 is required to reveal the active compound..

口委審定書 i
謝誌 ii
Abstract iv
摘要 v
目錄 vi
圖目錄 viii
表目錄 iix
縮寫表 x
第一章、 前言 1
第二章、 文獻回顧 2
第一節、 發炎與調控路徑 2
(一) 發炎反應 2
(二) 慢性發炎與慢性疾病 3
(三)發炎調控路徑 5
第二節、 中國橄欖與相關文獻 9
(一)中國橄欖簡介 9
(二)橄欖功效與其應用之模式 9
(三)中國橄欖化學成分及其功能研究 12
(四)目前橄欖抗發炎探討 23
第三章、 研究動機與實驗架構 24
第一節、 研究動機 24
第二節、 實驗架構與流程圖 25
第四章、 材料與方法 27
第一節、 實驗材料 27
(一) 中國橄欖甲醇萃取物乙酸乙酯區分層 27
(二) 試驗藥品 27
(三) 儀器設備 28
(四) 細胞來源與培養 29
第二節、 實驗方法 29
(一) 有效次區分層之溶劑分離 29
(二) 分離產物之次區分層分離 29
(三) 次區分層分離與純化 30
(四) COE-sup-D 11之主要成分純化與化合物鑑定 30
(五) 有效區分層之濱篙內酯(Scoparone)含量分析 31
(六) 細胞培養與冷光報導基因平台 32
第五章、 結果 34
第一節、 以溶劑效應作中國橄欖甲醇萃取物乙酸乙酯區分層之次區分層分離及其抗發炎效果之分析 34
第二節、 溶劑分離之上清液與矽膠管柱層析次區分層之抗發炎效果 41
第三節、 COE-sup-D與其經50% 乙酸乙酯/正己烷矽膠管柱分離之抗發炎效果 51
第四節、 COE-sup-D-no.11之主要成分純化與化合物鑑定結果 59
第五節、 有效區分層之濱篙內酯(Scoparone)含量分析 62
第六節、 純化產物的抗發炎功效驗證 67
第六章、 討論 73
(一)乙酸乙酯區分層之分離純化策略其產率與抗發炎效果比較 73
(二)中國橄欖甲醇萃取乙酸乙酯區分層已知成分之抗發炎機制 75
(三)有效區分層的細胞毒性 77
(四)濱篙內酯抗發炎途徑 78
(五)可能候選的抗發炎成分 79
第七章、 結論 80
第八章、 參考文獻 81

方麗娜，吳文珊，黃美麗，劉亮。2009。‘長營’橄欖果實揮發性成分分析。亞熱帶植物科學(02)。
王秀琦。2007。鞣花酸對於脂多醣體（LPS）誘導之小鼠巨噬細胞的抗發炎作用研究。亞洲大學碩士論文。台中市。
曲中堂，項昭保，趙志強。2010。橄欖總黃酮抑菌作用研究。中國釀造(04)，62-64。
朱良，趙冠欣，沈耀威，陳震。2010。橄欖總黃酮對小鼠急性酒精性肝損傷的保護作用。食品與機械(03)。
何穎，楊桂林，胡祥宇，袁葉飛。2012。青果總黃酮的抗炎作用研究。安徽農業科學(05)。
徐富翠，劉明華，孫玉紅，李茂，肖順漢。2014。青果抗炎鎮痛活性部位的篩選研究。中藥藥理與臨床(06) 。
邱詩婷。2011。建立並評估生物技術平台篩選具抗發炎效果食品。國立國立臺灣大學食品科技研究所碩士論文。台北市。
陳奕安。2012。利用細胞平台的評估進行中國橄欖萃取物中具抗發炎或抗腫瘤功效成分的分析與分離。國立國立臺灣大學食品科技研究所碩士論文。台北市。
陳榮，梁敬鈺，盧海英，楊洋，劉睿。2007。青橄欖葉的化學成分研究。林產化學與工業(02)。
楊潔，孫魏，楊旭銳，陳偉健，呂琳，段文軍。2008。青果抗人免疫缺陷病毒活性部位的篩選研究。中國藥房(21)。
葉昱德。2013。中國橄欖之抗增生活性因子的純化及鑑定暨其生理活性之研究。 國立國立臺灣大學食品科技研究所碩士論文。台北市。
張羽秀。2014。以活性導向方式分離中國橄欖果實內具抑制癌細胞增生之成分。國立國立臺灣大學食品科技研究所碩士論文。台北市。
Aggarwal, B. B., Shishodia, S., Sandur, S. K., Pandey, M. K., & Sethi, G. (2006). Inflammation and cancer: how hot is the link? Biochem Pharmacol, 72(11), 1605-1621.
Barton, G. M. (2008). A calculated response: control of inflammation by the innate immune system. Journal of Clinical Investigation, 118(2), 413-420.
Bellik, Y., Boukraa, L., Alzahrani, H. A., Bakhotmah, B. A., Abdellah, F., Hammoudi, S. M., & Iguer-Ouada, M. (2012). Molecular mechanism underlying anti-inflammatory and anti-allergic activities of phytochemicals: an update. Molecules, 18(1), 322-353.
Ben-Neriah, Y., & Karin, M. (2011). Inflammation meets cancer, with NF-κB as the matchmaker. Nature Immunology, 12(8), 715-723.
Bhoj, V. G., & Chen, Z. J. (2009). Ubiquitylation in innate and adaptive immunity. Nature, 458(7237), 430-437.
Calder, P. C. (2006). n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr, 83(6 Suppl), 1505s-1519s.
Calixto, J. B., Campos, M. M., Otuki, M. F., & Santos, A. R. (2004). Anti-inflammatory compounds of plant origin. Part II. modulation of pro-inflammatory cytokines, chemokines and adhesion molecules. Planta Med, 70(2), 93-103.
Calixto, J. B., Otuki, M. F., & Santos, A. R. (2003). Anti-inflammatory compounds of plant origin. Part I. Action on arachidonic acid pathway, nitric oxide and nuclear factor kappa B (NF-kappaB). Planta Med, 69(11), 973-983.
Carter, A. B., Knudtson, K. L., Monick, M. M., & Hunninghake, G. W. (1999). The p38 Mitogen-activated Protein Kinase Is Required for NF- B-dependent Gene Expression: THE ROLE OF TATA-BINDING PROTEIN (TBP). Journal of Biological Chemistry, 274(43), 30858-30863.
Chae, H. S., Kang, O. H., Choi, J. G., Oh, Y. C., Lee, Y. S., Brice, O. Kwon, D. Y. (2010). Methyl gallate inhibits the production of interleukin-6 and nitric oxide via down-regulation of extracellular-signal regulated protein kinase in RAW 264.7 cells. Am J Chin Med, 38(5), 973-983.
Chih-Chien, L. (2011). Antimicrobial, anti-tyrosinase and antioxidant activities of aqueous aromatic extracts from forty-eight selected herbs. Journal of Medicinal Plants Research, 5(26).
Choi, K. C., Lee, Y. H., Jung, M. G., Kwon, S. H., Kim, M. J., Jun, W. J., . . . Yoon, H. G. (2009). Gallic Acid Suppresses Lipopolysaccharide-Induced Nuclear Factor-kappa B Signaling by Preventing RelA Acetylation in A549 Lung Cancer Cells. Molecular Cancer Research, 7(12), 2011-2021.
Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420(6917), 860-867.
Dennis, L. K., Lynch, C. F., & Torner, J. C. (2002). Epidemiologic association between prostatitis and prostate cancer. Urology, 60(1), 78-83.
Donath, M. Y., & Shoelson, S. E. (2011). Type 2 diabetes as an inflammatory disease. Nat Rev Immunol, 11(2), 98-107.
Drexler, S. K., & Foxwell, B. M. (2010). The role of toll-like receptors in chronic inflammation. Int J Biochem Cell Biol, 42(4), 506-518.
Duan, W. J., Tan, S. Y., Chen, J., Liu, S. W., Jiang, S. B., Xiang, H. Y., & Xie, Y. (2013). Isolation of Anti-HIV Components from Canarium album Fruits by High-Speed Counter-Current Chromatography. Analytical Letters, 46(7), 1057-1068.
Dubois, R. N., Abramson, S. B., Crofford, L., Gupta, R. A., Simon, L. S., Van De Putte, L. B., & Lipsky, P. E. (1998). Cyclooxygenase in biology and disease. Faseb j, 12(12), 1063-1073.
Edderkaoui, M., Odinokova, I., Ohno, I., Gukovsky, I., Go, V. L. W., Pandol, S. J., & Gukovskaya, A. S. (2008). Ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells. World Journal of Gastroenterology : WJG, 14(23), 3672-3680.
Eisinger, A. L., Prescott, S. M., Jones, D. A., & Stafforini, D. M. (2007). The role of cyclooxygenase-2 and prostaglandins in colon cancer. Prostaglandins & Other Lipid Mediators, 82(1–4), 147-154.
Fan, Y., Mao, R., & Yang, J. (2013). NF-kappaB and STAT3 signaling pathways collaboratively link inflammation to cancer. Protein Cell, 4(3), 176-185.
Freund, A., Orjalo, A. V., Desprez, P. Y., & Campisi, J. (2010). Inflammatory networks during cellular senescence: causes and consequences. Trends in Molecular Medicine, 16(5), 238-246.
G.Eliopoulos, A., Dumitru, C. D., Wang, C.-C., Cho, J., & Tsichlis, P. N. (2002). Induction of COX-2 by LPS in macrophages is regulated by Tpl2-dependent CREB activation signals. The EMBO Journal, 21(18), 4831-4840.
Giang, P. M., Konig, W. A., & Son, P. T. (2006). Chemical composition of the resin essential oil of Canarium album from Vietnam. Chemistry of Natural Compounds, 42(5), 523-524.
Gil, J., & Esteban, M. (2000). Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): Mechanism of action. Apoptosis, 5(2), 107-114.
Grivennikov, S. I., Greten, F. R., & Karin, M. (2010). Immunity, Inflammation, and Cancer. Cell, 140(6), 883-899.
Guo, D. J., Cheng, H. L., Chan, S. W., & Yu, P. H. (2008). Antioxidative activities and the total phenolic contents of tonic Chinese medicinal herbs. Inflammopharmacology, 16(5), 201-207.
Hansson, G. K. (2005). Mechanisms of disease - Inflammation, atherosclerosis, and coronary artery disease. New England Journal of Medicine, 352(16), 1685-1695.
He, Z., & Xia, W. (2007a). Analysis of phenolic compounds in Chinese olive (Canarium album L.) fruit by RPHPLC–DAD–ESI–MS. Food Chemistry, 105(3), 1307-1311.
He, Z., & Xia, W. (2007b). Nutritional composition of the kernels from Canarium album L. Food Chemistry, 102(3), 808-811.
He, Z., Xia, W., & Chen, J. (2007). Isolation and structure elucidation of phenolic compounds in Chinese olive (Canarium album L.) fruit. European Food Research and Technology, 226(5), 1191-1196.
He, Z., Xia, W., Liu, Q., & Chen, J. (2008). Identification of a new phenolic compound from Chinese olive (Canarium album L.) fruit. European Food Research and Technology, 228(3), 339-343.
Held, T. K., Xiao, W. H., Liang, Y., Kalvakolanu, D. V., & Cross, A. S. (1999). Gamma interferon augments macrophage activation by lipopolysaccharide by two distinct mechanisms, at the signal transduction level and via an autocrine mechanism involving tumor necrosis factor alpha and interleukin-1. Infection and Immunity, 67(1), 206-212.
Hong, S. H., Jeong, H. K., Han, M. H., Park, C., & Choi, Y. H. (2014). Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-kappa B translocation in RAW 264.7 macrophages. Molecular Medicine Reports, 10(6), 3241-3246.
Ito, M., Shimura, H., Watanabe, N., Tamai, M., Hanada, K., Takahashi, A., . . . Wang, Y. L. (1990). HEPATOPROTECTIVE COMPOUNDS FROM CANARIUM-ALBUM AND EUPHORBIA-NEMATOCYPHA. Chemical & Pharmaceutical Bulletin, 38(8), 2201-2203.
Jang, S. I., Kim, Y. J., Lee, W. Y., Kwak, K. C., Baek, S. H., Kwak, G. B., . . . Chai, K. Y. (2005). Scoparone from Artemisia capillaris inhibits the release of inflammatory mediators in RAW 264.7 cells upon stimulation cells by interferon-gamma plus LPS. Archives of Pharmacal Research, 28(2), 203-208.
Kaminska, B. (2005). MAPK signalling pathways as molecular targets for anti-inflammatory therapy--from molecular mechanisms to therapeutic benefits. Biochim Biophys Acta, 1754(1-2), 253-262.
Kang, J. W., Kim, D. W., Choi, J. S., Kim, Y. S., & Lee, S. M. (2013). Scoparone attenuates D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure through inhibition of toll-like receptor 4 signaling in mice. Food and Chemical Toxicology, 57, 132-139.
Kim, E. K., Kwon, K. B., Lee, J. H., Park, B. H., Park, J. W., Lee, H. K., . . . Yang, J. Y. (2007). Inhibition of cytokine-mediated nitric oxide synthase expression in rat insulinoma cells by scoparone. Biological & Pharmaceutical Bulletin, 30(2), 242-246.
Kim, H. J., Jang, S. I., Kim, Y. J., Chung, H. T., Yun, Y. G., Kang, T. H., . . . Kim, Y. C. (2004). Scopoletin suppresses pro-inflammatory cytokines and PGE(2) from LPS-stimulated cell line, RAW 264.7 cells. Fitoterapia, 75(3-4), 261-266.
Kuan, N., Passaro, & Jr, E. (1998). Apoptosis: Programmed cell death. Archives of Surgery, 133(7), 773-775.
Kundu, J. K., & Surh, Y.-J. (2012). Emerging avenues linking inflammation and cancer. Free Radical Biology and Medicine, 52(9), 2013-2037.
Kuo, C. T., Liu, T. H., Hsu, T. H., Lin, F. Y., & Chen, H. Y. (2015). Antioxidant and antiglycation properties of different solvent extracts from Chinese olive (Canarium album L.) fruit. Asian Pacific Journal of Tropical Medicine, 8(12), 987-995.
Li, M. D., & Yang, X. Y. (2011). A Retrospective on Nuclear Receptor Regulation of Inflammation: Lessons from GR and PPARs. Ppar Research.
Libby, P. (2002). Inflammation in atherosclerosis. Nature, 420(6917), 868-874. Liu, H. Y., Qiu, N. X., Ding, H. H., & Yao, R. Q. (2008). Polyphenols contents and antioxidant capacity of 68 Chinese herbals suitable for medical or food uses. Food Research International, 41(4), 363-370.
Mühl, H., & Pfeilschifter, J. (2003). Anti-inflammatory properties of pro-inflammatory interferon-γ. International Immunopharmacology, 3(9), 1247-1255.
Ma, C. H., Ke, W., Sun, Z. L., Peng, J. Y., Li, Z. X., Zhou, X., . . . Huang, C. G. (2006). Large-scale isolation and purification of scoparone from Herba artemisiae scopariae by high-speed counter-current chromatography. Chromatographia, 64(1-2), 83-87.
Mantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008). Cancer-related inflammation. Nature, 454(7203), 436-444.
McInnes, I. B., & Schett, G. (2007). Cytokines in the pathogenesis of rheumatoid arthritis. Nature Reviews Immunology, 7(6), 429-442.
Mita, Y., Dobashi, K., Shimizu, Y., Nakazawa, T., & Mori, M. (2001). Toll-like receptor 2 and 4 surface expressions on human monocytes are modulated by interferon-gamma and macrophage colony-stimulating factor. Immunology Letters, 78(2), 97-101.
Monteiro, R., & Azevedo, I. (2010). Chronic inflammation in obesity and the metabolic syndrome. Mediators Inflamm, 2010.
Niu, N., Li, B., Hu, Y., Li, X., Li, J., & Zhang, H. (2014). Protective effects of scoparone against lipopolysaccharide-induced acute lung injury. International Immunopharmacology, 23(1), 127-133.
O''Connor, P. M., Lapointe, T. K., Beck, P. L., & Buret, A. G. (2010). Mechanisms by Which Inflammation May Increase Intestinal Cancer Risk in Inflammatory Bowel Disease. Inflammatory Bowel Diseases, 16(8), 1411-1420.
Patel, P. S., Buras, E. D., & Balasubramanyam, A. (2013). The role of the immune system in obesity and insulin resistance. J Obes, 2013, 616193.
Piccinini, A. M., & Midwood, K. S. (2010). DAMPening inflammation by modulating TLR signalling. Mediators Inflamm, 2010.
Rabtti, E. H. M. A., Natic, M. M., Milojkovic-Opsenica, D. M., Trifkovic, J. D., Tosti, T., Vuckovic, I. M., . . . Tesic, Z. L. (2012). Quantitative structure-toxicity relationship study of some natural and synthetic coumarins using retention parameters. Journal of the Serbian Chemical Society, 77(10), 1443-1456.
Raetz, C. R. H., & Whitfield, C. (2002). Lipopolysaccharide endotoxins. Annual Review of Biochemistry, 71, 635-700.
Ramana, C. V., Gil, M. P., Schreiber, R. D., & Stark, G. R. (2002). Stat1-dependent and -independent pathways in IFN-gamma-dependent signaling. Trends in Immunology, 23(2), 96-101.
Reilkoff, R. A., Bucala, R., & Herzog, E. L. (2011). Fibrocytes: emerging effector cells in chronic inflammation. Nature Reviews Immunology, 11(6), 427-435.
Sattar, N., McCarey, D. W., Capell, H., & McInnes, I. B. (2003). Explaining how "high-grade" systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation, 108(24), 2957-2963.
Schetter, A. J., Heegaard, N. H., & Harris, C. C. (2010). Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways. Carcinogenesis, 31(1), 37-49.
Schroder, K., Hertzog, P. J., Ravasi, T., & Hume, D. A. (2004). Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol, 75(2), 163-189.
Scott, D. L., Wolfe, F., & Huizinga, T. W. J. (2010). Rheumatoid arthritis. Lancet, 376(9746), 1094-1108.
Surh, Y. J., Chun, K. S., Cha, H. H., Han, S. S., Keum, Y. S., Park, K. K., & Lee, S. S. (2001). Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 480, 243-268.
Takeda, K., & Akira, S. (2004). TLR signaling pathways. Seminars in Immunology, 16(1), 3-9.
Tamai, M., Watanabe, N., Someya, M., Kondoh, H., Omura, S., Ling, Z. P., . . . Ming, C. W. (1989). NEW HEPATOPROTECTIVE TRITERPENES FROM CANARIUM-ALBUM. Planta Medica(1), 44-47.
Umesalma, S., & Sudhandiran, G. (2010). Differential inhibitory effects of the polyphenol ellagic acid on inflammatory mediators NF-kappaB, iNOS, COX-2, TNF-alpha, and IL-6 in 1,2-dimethylhydrazine-induced rat colon carcinogenesis. Basic Clin Pharmacol Toxicol, 107(2), 650-655.
Vichai, V., & Kirtikara, K. (2006). Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat. Protocols, 1(3), 1112-1116.
Waltz, P., Carchman, E. H., Young, A. C., Rao, J., Rosengart, M. R., Kaczorowski, D., & Zuckerbraun, B. S. (2011). Lipopolysaccaride induces autophagic signaling in macrophages via a TLR4, heme oxygenase-1 dependent pathway. Autophagy, 7(3), 315-320.
Wang, Y. C., & Huang, T. L. (2005). Screening of anti-Helicobacter pylori herbs deriving from Taiwanese folk medicinal plants. FEMS Immunol Med Microbiol, 43(2), 295-300.
Wei, H., Peng, W., Mao, Y., Liu, B., & Li, S. (1999). [Studies on chemical constituents in the fruit of Canarium album Raeusch]. Zhongguo Zhong Yao Za Zhi, 24(7), 421-423, 447.
Xiang, Z. B., Chen, H. S., Jin, Y. S., Wang, G. L., Xiang, L. X., & Chen, W. (2010). PHENOLIC CONSTITUENTS OF Canarium album. Chemistry of Natural Compounds, 46(1), 119-120.
Xu, H. Y., Barnes, G. T., Yang, Q., Tan, Q., Yang, D. S., Chou, C. J., . . . Chen, H. (2003). Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Journal of Clinical Investigation, 112(12), 1821-1830.
Yao, X. J., Ding, Z. Q., Xia, Y. F., Wei, Z. F., Luo, Y. B., Feleder, C., & Dai, Y. (2012). Inhibition of monosodium urate crystal-induced inflammation by scopoletin and underlying mechanisms. International Immunopharmacology, 14(4), 454-462.
Yoon, C. H., Chung, S. J., Lee, S. W., Park, Y. B., Lee, S. K., & Park, M. C. (2013). Gallic acid, a natural polyphenolic acid, induces apoptosis and inhibits proinflammatory gene expressions in rheumatoid arthritis fibroblast-like synoviocytes. Joint Bone Spine, 80(3), 274-279.
Zhang, L. L., & Lin, Y. M. (2008). Tannins from Canarium album with potent antioxidant activity. J Zhejiang Univ Sci B, 9(5), 407-415.
Zhao, B. X., Guang, H. J., Zhong, T. Q., Xing, G., & Lin, S. H. (2012). Chemical Constituents of Canarium album. Asian Journal of Chemistry, 24(10), 4829-4830.
박완수. (2010a). Inhibitory Effect of Gallic acid on Production of Chemokine and Growth Factor in Mouse Macrophage Stimulated by Lipopolysaccharide. [Gallic acid가 Lipopolysaccharide로 활성화된 마우스 대식세포의 케모카인과 성장인자 생성에 미치는 영향]. Korean Journal of Oriental Physiology & Pathology, 24(4), 586-591.
박완수. (2010b). Inhibitory Effect of Gallic acid on Production of Interleukins in Mouse Macrophage Stimulated by Lipopolysaccharide. [Gallic acid가 Lipopolysaccharide로 활성화된 마우스 대식세포의 인터루킨 생성에 미치는 영향]. Journal of Pharmacopuncture, 13(3), 63-71.