研究生: |
陳巧紋 Chen-Ciao-wen |
---|---|
論文名稱: |
山苦瓜葉萃取物對葡聚醣硫酸鈉誘導小鼠腸炎的保護效應與免疫調節之影響 Protective and immunoregulatory effects of wild bitter melon leaf extract on dextran sulfate sodium-induced murine colitis |
指導教授: |
蔡帛蓉
Tsai, Po-Jung 劉俊仁 Liu, Jun-Jen |
學位類別: |
碩士 Master |
系所名稱: |
人類發展與家庭學系 Department of Human Development and Family Studies |
論文出版年: | 2019 |
畢業學年度: | 107 |
語文別: | 中文 |
論文頁數: | 98 |
中文關鍵詞: | 發炎性腸道疾病 、山苦瓜葉 、腸道免疫 、調節型T淋巴細胞 、輔助型T淋巴細胞 、調節免疫 |
英文關鍵詞: | inflammatory bowel disease, wild bitter melon leaf, intestinal immunity, T helper cell, regulatory T cell, DSS-colitis |
DOI URL: | http://doi.org/10.6345/NTNU201900844 |
論文種類: | 學術論文 |
相關次數: | 點閱:120 下載:0 |
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發炎性腸道疾病 (inflammatory bowel disease, IBD)包括克隆氏症與潰瘍性腸炎,為一種慢性反覆發炎的免疫媒介疾病。在腸道免疫系統,輔助型T細胞 (helper T cell, Th)與調節型T細胞(regulatory T cell, Treg)的失衡被認為與IBD有關。山苦瓜葉(wild bitter melon leaf, WBML)具有抗發炎、調節免疫、抗氧化等生理活性。本研究以葡聚醣硫酸鈉(dextran sulfate sodium, DSS)誘導小鼠腸炎模式,探討介入WBML對於腸炎疾病的可能保護功效與其作用機轉。
首先觀察預先給予WBML (4種山苦瓜品系:HL-2、HL-3、#1621、#8123) 預防性減緩腸炎的效應。將C57BL/6J小鼠分為正常控制組、腸炎組(DSS組)和DSS+EE (山苦瓜葉乙醇萃取物, ethanol extract)組,先管餵EE經1週後停止介入,再以3 % DSS誘導急性腸炎經5天後進行犧牲觀察,發現4種品系EE均能顯著降低血液中B cell、T cell以及Th1、Th2、Th17比率,推測WBML具免疫調節和緩解腸炎的潛力,其中以HL-3的效果較佳因此選用該品系進行後續實驗。
實驗二,將小鼠分為正常控制組、DSS組及DSS+WBML組(分別為餵食山苦瓜全葉乾燥粉末(whole leaf, WL)組、EE組和富含三萜類之區分物 (triterpenoid enriched-extract, TEE)組),管餵1週後再以3.5 % DSS 誘導急性腸炎並持續給予WL、EE、TEE經7天後犧牲。結果發現TEE顯著減緩腸炎小鼠體重減輕、疾病活動指數 (DAI)、脾臟重量增加情形和降低糞便lipocalin-2、大腸組織ICAM-1和腸腔沖洗液CCL2 (MCP-1)濃度。從組織病理切片觀察,TEE顯著降低DSS誘導腸炎的嚴重程度。而EE顯著減少腸腔沖洗液TNF-α和CCL2濃度。WL顯著降低腹腔沖洗液(PCW)中neutrophil、B cell 及血液中macrophage比率,EE能顯著減少PCW中neutrophil、macrophage、B cell 及血液中neutrophil、B cell 比率。TEE顯著抑制PCW中B cell及血液中neutrophil比率。進一步分析血液中T細胞次群,發現EE和TEE均顯著抑制 Th1比率,EE 顯著抑制Th2比率,而WL、EE、TEE皆能顯著抑制血液中Th17 比率並提高Treg比率。與DSS組比較,WL、EE、TEE組的腸繫膜淋巴結T-bet (Th) mRNA表現量皆較低,而Foxp3 (Treg) mRNA表現量皆增加,其中TEE組達顯著差異。本研究結果推測WBML可藉由調控DSS誘發腸炎造成之Th/Treg 失衡,具有緩解腸炎的潛力。
Inflammatory bowel disease (IBD), a dysregulated immune inflammatory state of the gastrointestinal tract, is classified into two archetypal phenotypes: Crohn's disease (CD) and ulcerative colitis (UC). A dysregulated intestinal T cell response is presumed in patients with IBD. An altered balance between Treg cells and T effector cells in the intestinal microenvironment might contribute to the pathogenesis of IBD. Wild bitter melon (WBM; Momordica charantia L.var.abbreviata Seringe), a variety of bitter melon, possesses several biological activities. The aim of this study was to investigate the protective potential of WBM leaf (WBML) against dextran sulfate sodium (DSS)-induced murine colitis.
First, C57BL/6 mice were randomly divided into six groups: one normal control (NC) group and five DSS-treated groups, including DSS group (colitis model) and the ethanol extract (EE) of WBML (WBM cultivars: HL-2, HL-3, #1621, and #8123) treatment groups. The results showed that 1-week pre-treatment of all of four EE significantly reduced B cell and T cell populations, and ratios of Th1, Th2, Th17 in blood. Our data suggested that WBML might ameliorate DSS-induced colitis, especially the HL-3 cultivar. Hence, WBML from HL-3 was used for subsequent experiments.
Next, we prepared WBML samples including whole leaf (WL) and its extracts (EE and triterpenoid enriched-extract, TEE). C57BL/6 mice were randomly divided into five groups: one normal control (NC) group and four DSS-treated groups, including DSS group (colitis model), WL group (DSS+ WL), EE group (DSS+EE) and TEE group (DSS+TEE). The DSS-treated groups drank distilled water containing 3.5% DSS for 7 d to induce colitis, while NC group drank distilled water. WL, EE, and TEE groups was respectively administrated by oral gavage with WL (700 mg/kg BW), EE (100 mg/kg BW), and TEE (70 mg/kg BW) for 7 days before DSS-induced colitis and subsequently received WL, EE, or TEE after DSS-induced colitis for 7 days. Our results showed that TEE significantly ameliorated DSS-induced mice weight loss, disease activity index (DAI), colon shortening, colonic CCL2 (MCP-1), colonic intercellular cell adhesion molecule-1 (ICAM-1), and fecal lipocalin-2 levels. In addition, TEE reduced the severity of DSS-induced histopathology in the colon. WL supplementation significantly reduced the proportion of peritoneal neutrophil and B cell and the proportion of macrophage in blood. EE supplementation significantly reduced the proportion of peritoneal neutrophil macrophage, and B cell and the proportion of neutrophil in blood. TEE supplementation significantly reduced the proportion of peritoneal B cell and the proportion of neutrophil and B cell in blood. All three WBM treatments significantly decreased Th17 proportion and enhanced Treg proportion. In addition, TEE significantly lowered Th2. All three groups significantly inhibited T-bet mRNA expression (Th1) in spleen and mesenteric lymph nodes. Moreover, TEE supplementation significantly increased foxp3 mRNA expression (Treg) in spleen and mesenteric lymph nodes.
In conclusion, these results suggested that WBML treatment regulated Th/Treg-mediated immunity and may consequently attenuate inflammatory responses, thus improving the symptoms of colitis in DSS-treated mice.
一、中文文獻
全中和。2001。珍貴種源山苦瓜。花蓮區農業專訊。
宇文靖。2014。這樣吃苦瓜,糖尿病來也不怕。臺北市:人本自然。
財團法人食品工業發展研究所。1998。花蓮1號、花蓮2號及花蓮3號營養成分。
黃文程(2016)。生物活性導向分離鑑定山苦瓜緩解痤瘡丙酸桿菌誘導發炎反應之活性成分。國立臺灣師範大學人類發展與家庭學系博士論文。未出版。
趙涓含(2016)。苦瓜三萜類化合物TCD對人類胃癌AGS細胞的抗腫瘤效應及增加化學治療的敏感性。國立臺灣師範大學人類發展與家庭學系碩士論文。未出版。
石雅欣(2016)。以痤瘡桿菌刺激單核球細胞為模式探討山苦瓜葉萃取物之區分物抑制 IL-8 生成。國立臺灣師範大學人類發展與家庭學系碩士論文,台北市。 取自https://hdl.handle.net/11296/k5ytd9
二、英文文獻
Abegunde, A. T., Muhammad, B. H., &Ali, T. (2016). Preventive health measures in inflammatory bowel disease. World Journal of Gastroenterology, 22(34), 7625. https://doi.org/10.3748/wjg.v22.i34.7625
Alhassan Mohammed, H., Mirshafiey, A., Vahedi, H., Hemmasi, G., Moussavi Nasl Khameneh, A., Parastouei, K., & Saboor‐Yaraghi, A. A. (2017). Immunoregulation of inflammatory and inhibitory cytokines by vitamin D 3 in patients with inflammatory bowel diseases. Scandinavian Journal of Immunology, 85(6), 386-394.
Ananthakrishnan, A. N. (2015). Epidemiology and risk factors for IBD. Nature Reviews Gastroenterology and Hepatology, 12(4), 205. https://doi.org/10.1038/nrgastro.2015.34
Anthony, R. M., Rutitzky, L. I., Urban, J. F., Stadecker, M. J., &Gause, W. C. (2007). Protective immune mechanisms in helminth infection. Nature Reviews Immunology, 7(12), 975. https://doi.org/10.1038/nri2199
Araki, A., Kanai, T., Ishikura, T., Makita, S., Uraushihara, K., Iiyama, R., …Watanabe, M. (2005). MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis. Journal of Gastroenterology, 40(1), 16-23. https://doi.org/10.1007/s00535-004-1492-9
Atreya, I., Atreya, R., &Neurath, M. F. (2008). NF-kappaB in inflammatory bowel disease. Journal of Internal Medicine, 263(6), 591-596. https://doi.org/10.1111/j.1365-2796.2008.01953.x
Baek, H. J., Jeong, Y. J., Kwon, J. E., Ra, J. S., Lee, S. R., & Kang, S. C. (2018). Antihyperglycemic and Antilipidemic Effects of the Ethanol Extract Mixture of Ligularia fischeri and Momordica charantia in Type II Diabetes-Mimicking Mice.Evidence-Based Complementary and Alternative Medicine, 2018. https://doi.org/ 10.1155/2018/3468040.
Bai, J., Zhu, Y., &Dong, Y. (2016). Response of gut microbiota and inflammatory status to bitter melon (Momordica charantia L.) in high fat diet induced obese rats. Journal of Ethnopharmacology, 194, 717-726. https://doi.org/10.1016/j.jep.2016.10.043
Bai, J., Zhu, Y., &Dong, Y. (2017). Bitter Melon Powder Protects against Obesity-associated Fatty Liver Disease by Improving Colonic Microenvironment in Rats with High-fat Diet-induced Obesity .Biomed Environ Sci, 30(8), 611-615. https://doi.org/10.3967/bes2017.081
Bao, B., Chen, Y. G., Zhang, L., Xu, Y. L. N., Wang, X., Liu, J., &Qu, W. (2013). Momordica charantia (Bitter Melon) reduces obesity-associated macrophage and mast cell infiltration as well as inflammatory cytokine expression in adipose tissues. .PLoS One, 8(12), e84075. https://doi.org/10.1371/journal.pone.0084075
Baumann, H., &Gauldie, J. (1994). The acute phase response. Immunology Today, 15(2), 74-80.
Begue, B., Wajant, H., Bambou, J. C., Dubuquoy, L., Siegmund, D., Beaulieu, J. F., …Ruemmele, F. M. (2006). Implication of TNF-Related Apoptosis-Inducing Ligand in Inflammatory Intestinal Epithelial Lesions. Gastroenterology, 130(7), 1962-1974. https://doi.org/10.1053/j.gastro.2006.03.022
Beloin, N., Gbeassor, M., Akpagana, K., Hudson, J., DeSoussa, K., Koumaglo, K., &Arnason, J. T. (2005). Ethnomedicinal uses of Momordica charantia (Cucurbitaceae) in Togo and relation to its phytochemistry and biological activity. Journal of Ethnopharmacology, 96(1-2), 49-55. https://doi.org/10.1016/j.jep.2004.08.009
Ben-Horin, S., Mao, R., & Chen, M. (2015). Optimizing biologic treatment in IBD: objective measures, but when, how and how often?. BMC Gastroenterology, 15(1), 178.
Benchimol, E. I., Mack, D. R., Guttmann, A., Nguyen, G. C., To, T., Mojaverian, N., …Manuel, D. G. (2015). Inflammatory bowel disease in immigrants to Canada and their children: A population-based cohort study. The American Journal of Gastroenterology, 110(4), 553. https://doi.org/10.1038/ajg.2015.52
Bendjelloul, F., Malý, P., Mandys, V., Jirkovská, M., Prokešová, L., Tučková, L., &Tlaskalová-Hogenová, H. (2000). Intercellular adhesion molecule-1 (ICAM-1) deficiency protects mice against severe forms of experimentally induced colitis. Clinical & Experimental Immunology, 119(1), 57-63. https://doi.org/10.1046/j.1365-2249.2000.01090.x
Bernstein, C. N., &Forbes, J. D. (2017). Gut Microbiome in Inflammatory Bowel Disease and Other Chronic Immune-Mediated Inflammatory Diseases. Inflammatory Intestinal Diseases, 2(2), 116-123. https://doi.org/10.1159/000481401
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., …Kuchroo, V. K. (2006). Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature,441(7090), 235. https://doi.org/10.1038/nature04753
Bluestone, J. A., &Abbas, A. K. (2003). Opinion-regulatory lymphocytes: natural versus adaptive regulatory T cells. Nature Reviews Immunology, 3(3), 253. https://doi.org/10.1038/nri1032
Boirivant, M., Fuss, I. J., Chu, A., &Strober, W. (1998). Oxazolone Colitis: A Murine Model of T Helper Cell Type 2 Colitis Treatable with Antibodies to Interleukin 4. Journal of Experimental Medicine, 188(10), 1929-1939. https://doi.org/10.1084/jem.188.10.1929
Bortolotti, M., Mercatelli, D., &Polito, L. (2019). Momordica charantia, a Nutraceutical Approach for Inflammatory Related Diseases. Frontiers in Pharmacology, 10, 486. https://doi.org/10.3389/fphar.2019.00486
Callewaere, C., Banisadr, G., Rostène, W., &Parsadaniantz, S. M. (2007). Chemokines and chemokine receptors in the brain: Implication in neuroendocrine regulation. Journal of Molecular Endocrinology, 38(3), 355-363. https://doi.org/10.1677/JME-06-0035
Celiberto, L. S., Graef, F. A., Healey, G. R., Bosman, E. S., Jacobson, K., Sly, L. M., &Vallance, B. A. (2018). Inflammatory bowel disease and immunonutrition: novel therapeutic approaches through modulation of diet and the gut microbiome. Immunology, 155(1), 36-52. https://doi.org/10.1111/imm.12939
Chanda, J., Mukherjee, P. K., Biswas, R., Malakar, D., & Pillai, M. (2019). Study of pancreatic lipase inhibition kinetics and LC-QTOF-MS-based identification of bioactive constituents of Momordica charantia fruits. Biomedical Chromatography, 33(4), e4463. https://doi.org/10.1002/bmc.4463
Chao, C. Y., Sung, P. J., Wang, W. H., &Kuo, Y. H. (2014). Anti-inflammatory effect of momordica charantia in sepsis mice. Molecules, 19(8), 12777-12788. https://doi.org/10.3390/molecules190812777
Chassaing, B., Aitken, J. D., Malleshappa, M., & Vijay‐Kumar, M. (2014). Dextran sulfate sodium (DSS)‐induced colitis in mice. Current Protocols in Immunology, 104(1), 15-25.
Chassaing, B., Srinivasan, G., Delgado, M. A., Young, A. N., Gewirtz, A. T., &Vijay-Kumar, M. (2012). Fecal Lipocalin 2, a Sensitive and Broadly Dynamic Non-Invasive Biomarker for Intestinal Inflammation. PloS One, 7(9), e44328. https://doi.org/10.1371/journal.pone.0044328
Chen, Y., Liu, W., Sun, T., Huang, Y., Wang, Y., Deb, D. K., ... & Li, Y. C. (2013). 1, 25-Dihydroxyvitamin D promotes negative feedback regulation of TLR signaling via targeting MicroRNA-155–SOCS1 in macrophages. The Journal of Immunology, 190(7), 3687-3695.
Choi, I. Y., Piccio, L., Childress, P., Bollman, B., Ghosh, A., Brandhorst, S., ... & Wei, M. (2016). A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms. Cell Reports, 15(10), 2136-2146.
Colombel, J. F., Sandborn, W. J., Reinisch, W., Mantzaris, G. J., Kornbluth, A., Rachmilewitz, D., ... & Tang, K. L. (2010). Infliximab, azathioprine, or combination therapy for Crohn's disease. New England Journal of Medicine, 362(15), 1383-1395.
Comi, C., Leone, M., Bonissoni, S., DeFranco, S., Bottarel, F., Mezzatesta, C., …Dianzani, U. (2000). Defective T cell Fas function in patients with multiple sclerosis. Neurology, 55(7), 921-927. https://doi.org/10.1212/WNL.55.7.921
Cooper, H. S., Murthy, S. N., Shah, R. S., &Sedergran, D. J. (1993). Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Laboratory Investigation; a Journal of Technical Methods and Pathology, 69(2), 238-249.
Cosnes, J., Gowerrousseau, C., Seksik, P., &Cortot, A. (2011). Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology, 140(6), 1785-1794. https://doi.org/10.1053/j.gastro.2011.01.055
Costabile, A., Kolida, S., Klinder, A., Gietl, E., Bäuerlein, M., Frohberg, C., ... & Gibson, G. R. (2010). A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects. British Journal of Nutrition, 104(7), 1007-1017.
Cherbut, C., Michel, C., & Lecannu, G. (2003). The prebiotic characteristics of fructooligosaccharides are necessary for reduction of TNBS-induced colitis in rats. The Journal of nutrition, 133(1), 21-27.
Chuang, C. Y., Hsu, C., Chao, C. Y., Wein, Y. S., Kuo, Y. H., &Huang, C. J. (2006). Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as an activator of PPARα in bitter gourd (Momordica charantia L.). Journal of Biomedical Science, 13(6), 763-772. https://doi.org/10.1007/s11373-006-9109-3
De Cruz, P., Kamm, M. A., Prideaux, L., Allen, P. B., & Desmond, P. V. (2011). Postoperative recurrent luminal Crohn's disease: a systematic review. Inflammatory Bowel Diseases, 18(4), 758-777.
De Mattos, B. R. R., Garcia, M. P. G., Nogueira, J. B., Paiatto, L. N., Albuquerque, C. G., Souza, C. L., …Simioni, P. U. (2015). Inflammatory bowel disease: An overview of immune mechanisms and biological treatments. Mediators of Inflammation. https://doi.org/10.1155/2015/493012
De Rosa, V., La Cava, A., & Matarese, G. (2017). Metabolic pressure and the breach of immunological self-tolerance. Nature Immunology, 18(11), 1190.
Deng, Y. Y., Yi, Y., Zhang, L. F., Zhang, R. F., Zhang, Y., Wei, Z. C., …Zhang, M. W. (2014). Immunomodulatory activity and partial characterisation of polysaccharides from Momordica charantia. Molecules, 19(9), 13432-13447. https://doi.org/10.3390/molecules190913432
Dubinsky, M., &Braun, J. (2015). Diagnostic and Prognostic Microbial Biomarkers in Inflammatory Bowel Diseases. Gastroenterology, 149(5), 1265-1274 .https://doi.org/10.1053/j.gastro.2015.08.006
Deshmane, S. L., Kremlev, S., Amini, S., & Sawaya, B. E. (2009). Monocyte chemoattractant protein-1 (MCP-1): an overview. Journal of Interferon & Cytokine Research, 29(6), 313-326.
Eastaff-Leung, N., Mabarrack, N., Barbour, A., Cummins, A., &Barry, S. (2010). Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease. Journal of Clinical Immunology, 30(1), 80-89. https://doi.org/10.1007/s10875-009-9345-1
Eichele, D. D., &Kharbanda, K. K. (2017). Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis. World Journal of Gastroenterology, 23(33), 6016. https://doi.org/10.3748/wjg.v23.i33.6016
Elson, C. O., Sartor, R. B., Tennyson, G. S., & Riddell, R. H. (1995). Experimental models of inflammatory bowel disease. Gastroenterology, 109(4), 1344-1367.
Engelhardt, K. R., &Grimbacher, B. (2014). IL-10 in humans: Lessons from the Gut, IL-10/IL-10 receptor deficiencies, and IL-10 polymorphisms. In Interleukin-10 in Health and Disease (pp. 1-18). Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-43492-5_1
Fachinan, R., Yessoufou, A., Nekoua, M. P., &Moutairou, K. (2017). Effectiveness of Antihyperglycemic Effect of Momordica charantia: Implication of T-Cell Cytokines. Evidence-Based Complementary and Alternative Medicine, 2017. https://doi.org/10.1155/2017/3707046
Faria, A. M. C., Mucida, D., McCafferty, D. M., Tsuji, N. M., &Verhasselt, V. (2012). Tolerance and inflammation at the gut mucosa. Clinical and Developmental Immunology. https://doi.org/10.1155/2012/738475
Ferreira, G. B., Vanherwegen, A. S., Eelen, G., Gutiérrez, A. C. F., Van Lommel, L., Marchal, K., ... & Schuit, F. (2015). Vitamin D3 induces tolerance in human dendritic cells by activation of intracellular metabolic pathways. Cell Reports, 10(5), 711-725.
Fiorucci, S., Mencarelli, A., Palazzetti, B., Sprague, A. G., Distrutti, E., Morelli, A., …DeFougerolles, A. R. (2002). Importance of innate immunity and collagen binding integrin α1β1 in TNBS-induced colitis. Immunity, 17(6), 769-780. https://doi.org/10.1016/S1074-7613(02)00476-4
Foersch, S., Waldner, M. J., &Neurath, M. F. (2013). Innate and adaptive immunity in inflammatory bowel diseases. Digestive Diseases, 31(3-4), 317-320.https://doi.org/10.1159/000354685
Frank, P. G., &Lisanti, M. P. (2008). ICAM-1: role in inflammation and in the regulation of vascular permeability. American Journal of Physiology-Heart and Circulatory Physiology, 295(3), H926-H927. https://doi.org/10.1152/ajpheart.00779.2008
Fukata, M. (2005). Toll-like receptor-4 is required for intestinal response to epithelial injury and limiting bacterial translocation in a murine model of acute colitis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 288(5), G1055-G1065. https://doi.org/10.1152/ajpgi.00328.2004
Fukata, M., &Arditi, M. (2013). The role of pattern recognition receptors in intestinal inflammation. Mucosal Immunology, 6(3), 451. https://doi.org/10.1038/mi.2013.13
Gagliani, N., Amezcua Vesely, M. C., Iseppon, A., Brockmann, L., Xu, H., Palm, N. W., …Flavell, R. A. (2015). TH17 cells transdifferentiate into regulatory T cells uring resolution of inflammation. Nature, 523(7559), 221. https://doi.org/10.1038/nature14452
Gálvez, J. (2014). Role of Th17 Cells in the Pathogenesis of Human IBD. ISRN Inflammation. ISRN Inflammation, 2014. https://doi.org/10.1155/2014/928461
Gao, Z., Li, Q., Wu, X., Zhao, X., Zhao, L., &Tong, X. (2017). New Insights into the Mechanisms of Chinese Herbal Products on Diabetes: A Focus on the “bacteria-Mucosal Immunity-Inflammation-Diabetes” Axis. Journal of Immunology Research, 2017. https://doi.org/10.1155/2017/1813086
Generali E Folci M Selmi C Riboldi P. (2017). In The Immunology of Cardiovascular Homeostasis and Pathology (pp. 145-171). Springer, Cham.. https://doi.org/ 10.1007/978-3-319-57613-8_8
Goyal, N., Rana, A., Ahlawat, A., Bijjem, K. R.V., &Kumar, P. (2014). Animal models of inflammatory bowel disease: Inflammopharmacology, 22(4), 219-233. https://doi.org/10.1007/s10787-014-0207-y
Griga, T., Hebler, U., Voigt, E., Tromm, A., &May, B. (2000). Interleukin-4 inhibits the increased production of vascular endothelial growth factor by peripheral blood mononuclear cells in patients with inflammatory bowel disease. Hepato-Gastroenterology, 47(36), 1604-1607.
Guinane, C. M., &Cotter, P. D. (2013). Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ. Therapeutic Advances in Gastroenterology, 6(4), 295-308. https://doi.org/10.1177/1756283X13482996
Hall, L. J., Faivre, E., Quinlan, A., Shanahan, F., Nally, K., & Melgar, S. (2011). Induction and activation of adaptive immune populations during acute and chronic phases of a murine model of experimental colitis. Digestive Diseases and Sciences, 56(1), 79-89
Hanauer, S. B., Feagan, B. G., Lichtenstein, G. R., Mayer, L. F., Schreiber, S., Colombel, J. F., ... & Rutgeerts, P. (2002). Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. The Lancet, 359(9317), 1541-1549.
Han, L., Yang, J., Wang, X., Li, D., Lv, L., &Li, B. (2015). Th17 cells in autoimmune diseases. Frontiers of Medicine, 9(1), 10-19. https://doi.org/10.1007/s11684-015-0388-9
Heller, F., Fuss, I. J., Nieuwenhuis, E. E., Blumberg, R. S., &Strober, W. (2002). Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity, 17(5), 629-638. https://doi.org/10.1016/S1074-7613(02)00453-3
Hendrickson, B. A., Gokhale, R., & Cho, J. H. (2002). Clinical aspects and pathophysiology of inflammatory bowel disease. Clinical Microbiology Reviews, 15(1), 79-94.
Hsu, C., Tsai, T. H., Li, Y. Y., Wu, W. H., Huang, C. J., &Tsai, P. J. (2012). Wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.) extract and its bioactive components suppress Propionibacterium acnes-induced inflammation. Food Chemistry, 135(3), 976-984. https://doi.org/10.1016/j.foodchem.2012.05.045
Hu, D., Notarbartolo, S., Croonenborghs, T., Patel, B., Cialic, R., Yang, T. H., …Weiner, H. L. (2017). Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis. Nature Communications, 8(1), 1600. https://doi.org/10.1038/s41467-017-01571-8
Huang, W. C., Tsai, T. H., Huang, C. J., Li, Y. Y., Chyuan, J. H., Chuang, L.Te, &Tsai, P. J. (2015). Inhibitory effects of wild bitter melon leaf extract on Propionibacterium acnes-induced skin inflammation in mice and cytokine production in vitro. Food & Function, 6(8), 2550-2560. https://doi.org/10.1039/c5fo00550g
Huang, Y., &Chen, Z. (2016). Inflammatory bowel disease related innate immunity and adaptive immunity. American Journal of Translational Research, 8(6), 2490.https://doi.org/10.1103/PhysRevB.77.195421
Huber, S., Gagliani, N., Esplugues, E., O’Connor, W., Huber, F. J., Chaudhry, A., …Flavell, R. A. (2011). Th17 Cells Express Interleukin-10 Receptor and Are Controlled by Foxp3-and Foxp3+Regulatory CD4+T Cells in an Interleukin-10-Dependent Manner. Immunity, 34(4), 554-565. https://doi.org/10.1016/j.immuni.2011.01.020
Hussan, F., Teoh, S. L., Muhamad, N., Mazlan, M., &Latiff, A. A. (2014). Momordica charantia ointment accelerates diabetic wound healing and enhances transforming growth factor-β expression. Journal of Wound Care, 23(8), 400-407.https://doi.org/10.12968/jowc.2014.23.8.400
Ichiyama, K., Yoshida, H., Wakabayashi, Y., Chinen, T., Saeki, K., Nakaya, M., …Kobayashi, T. (2008). Foxp3 inhibits RORγt-mediated IL-17A mRNA transcription through direct interaction with RORγt. Journal of Biological Chemistry, 283(25), 17003-17008. https://doi.org/10.1074/jbc.M801286200
Imam, T., Park, S., Kaplan, M. H., & Olson, M. R. (2018). Effector T helper cell subsets in inflammatory bowel diseases. Frontiers in Immunology, 9.
Jabeen, U., &Khanum, A. (2017). Isolation and characterization of potential food preservative peptide from Momordica charantia L. Arabian Journal of Chemistry, 283(25), 17003-17008. https://doi.org/10.1016/j.arabjc.2014.06.009
Jia, S., Shen, M., Zhang, F., &Xie, J. (2017). Recent advances in momordica charantia: Functional components and biological activities. International Journal of Molecular Sciences, 18(12), 2555. https://doi.org/10.3390/ijms18122555
Jiminez, J. A., Uwiera, T. C., Inglis, G. D., &Uwiera, R. R. E. (2015). Animal models to study acute and chronic intestinal inflammation in mammals. Gut Pathogens, 18(12), 2555. https://doi.org/10.1186/s13099-015-0076-y
Jin, D., Wu, S., Zhang, Y. G., Lu, R., Xia, Y., Dong, H., & Sun, J. (2015). Lack of vitamin D receptor causes dysbiosis and changes the functions of the murine intestinal microbiome. Clinical Therapeutics, 37(5), 996-1009.
Kanazawa, S., Tsunoda, T., Onuma, E., Majima, T., Kagiyama, M., &Kikuchi, K. (2001). VEGF, basic-FGF, and TGF-β in Crohn’s disease and ulcerative colitis: A novel mechanism of chronic intestinal inflammation. American Journal of Gastroenterology, 96(3), 822. https://doi.org/10.1016/S0002-9270(00)02320-0
Kang, J., Zeng, B., Tang, S., Wang, M., Han, X., Zhou, C., …Tan, Z. (2017). Effects of Momordica charantia polysaccharide on in vitro ruminal fermentation and cellulolytic bacteria. Italian Journal of Animal Science, 16(2), 226–233. https://doi.org/10.1080/1828051X.2017.1289825
Kaplan, G. G., Hubbard, J., Korzenik, J., Sands, B. E., Panaccione, R., Ghosh, S., …Villeneuve, P. J. (2010). The inflammatory bowel diseases and ambient air pollution: A novel association. American Journal of Gastroenterology, 105(11), 2412. https://doi.org/10.1038/ajg.2010.252
Kawada, M., Arihiro, A., &Mizoguchi, E. (2007). Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease. World Journal of Gastroenterology, 13(42), 5581. https://doi.org/10.3748/wjg.v13.i42.5581
Kedia, S., & Ahuja, V. (2017). Epidemiology of inflammatory bowel disease in India: the great shift east. Inflammatory Intestinal Diseases, 2(2), 102-115.
Kenny, O., Smyth, T. J., Hewage, C. M., &Brunton, N. P. (2013). Antioxidant properties and quantitative UPLC-MS analysis of phenolic compounds from extracts of fenugreek (Trigonella foenum-graecum) seeds and bitter melon (Momordica charantia) fruit. Food Chemistry, 141(4), 4295-4302. https://doi.org/10.1016/j.foodchem.2013.07.016
Ke, X. I. A., Fang, Y. A. N., Yang, Y. E., & Lin, T. A. N. G. (2007). The effect of the total saponin extract from the seeds of Momordica charantia L. on anti-virus HSV-Ⅰ and RSV activity [J]. Journal of Sichuan University (Natural Science Edition), 1.
Kiesler, P., Fuss, I. J., &Strober, W. (2001). Experimental models of inflammatory bowel diseases. Medecine et Hygiene, 1(2), 154-170. https://doi.org/10.1016/j.jcmgh.2015.01.006
Kim, M. H., &Kim, H. (2017). The roles of glutamine in the intestine and its implication in intestinal diseases. International Journal of Molecular Sciences ,18(5), 1051. https://doi.org/10.3390/ijms18051051
Knights, D., Lassen, K. G., &Xavier, R. J. (2013). Advances in inflammatory bowel disease pathogenesis: Linking host genetics and the microbiome. Gut ,62(10), 1505-1510. https://doi.org/10.1136/gutjnl-2012-303954
Kinoshita H Ogata Y. (2018). Effect of Bitter Melon Extracts on Lipid Levels in Japanese Subjects: A Randomized Controlled Study. Evidence-based complementary and alternative medicine, 2018. https://doi.org/ 10.1155/2018/4915784
Knowles, S., Andrews, J. M., &Porter, A. (2018). Predictors of impaired mental health and support seeking in adults with inflammatory bowel disease. Gastroenterology Nursing, 41(1), 38-46. https://doi.org/10.1097/SGA.0000000000000251
Kobayashi, K., Kaneda, K., &Kasama, T. (2001). Immunopathogenesis of delayed-type hypersensitivity. Microscopy Research and Technique, 53(4), 241-245. https://doi.org/10.1002/jemt.1090
Kubola, J., &Siriamornpun, S. (2008). Phenolic contents and antioxidant activities of bitter gourd (Momordica charantia L.) leaf, stem and fruit fraction extracts in vitro. Food Chemistry, 110(4), 881-890. https://doi.org/10.1016/j.foodchem.2008.02.076
Kwon, S. H., Seo, E. B., Lee, S. H., Cho, C. H., Kim, S. J., Kim, S. J., ... & Ye, S. K. (2018). T Cell-Specific Knockout of STAT3 Ameliorates Dextran Sulfate Sodium-Induced Colitis by Reducing the Inflammatory Response. Immune Network, 18(4).
Larsen, N., Vogensen, F. K., Van DenBerg, F. W. J., Nielsen, D. S., Andreasen, A. S., Pedersen, B. K., …Jakobsen, M. (2010). Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE ,5(2), e9085. https://doi.org/10.1371/journal.pone.0009085
Lawrance, Ian C., Wu, F., Leite, A. Z. A., Willis, J., West, G. A., Fiocchi, C., &Chakravarti, S. (2003). A Murine Model of Chronic Inflammation-Induced Intestinal Fibrosis Down-Regulated by Antisense NF-κB. Gastroenterology ,125(6), 1750-1761. https://doi.org/10.1053/j.gastro.2003.08.027
Lawrance, Ian Craig, Maxwell, L., &Doe, W. (2001). Altered response of intestinal mucosal fibroblasts to profibrogenic cytokines in inflammatory bowel disease. Inflammatory Bowel Diseases, 7(3), 226-236. https://doi.org/10.1097/00054725-200108000-00008
Lee, S. H., eun Kwon, J., & Cho, M. L. (2018). Immunological pathogenesis of inflammatory bowel disease. Intestinal Research, 16(1), 26.
Li, M. O., &Flavell, R. A. (2008). TGF-beta: a master of all T cell trades. Cell, 134(3), 392-404. https://doi.org/10.1016/j.cell.2008.07.025
Limdi, J. K. (2018). Dietary practices and inflammatory bowel disease. Indian Journal of Gastroenterology, 37(4), 284-292. https://doi.org/10.1007/s12664-018-0890-5
Liu, T., Zhang, L., Joo, D., &Sun, S.-C. (2017). NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy, 2, 17023. https://doi.org/10.1038/sigtrans.2017.23
Lu, H. Y., & Lin, B. F. (2016). Wild bitter melon alleviates dextran sulphate sodium-induced murine colitis by suppressing inflammatory responses and enhancing intestinal regulatory T cells. Journal of Functional Foods, 23, 590-600.
Lu, K. H., Tseng, H. C., Liu, C. T., Huang, C. J., Chyuan, J. H., &Sheen, L. Y. (2014). Wild bitter gourd protects against alcoholic fatty liver in mice by attenuating oxidative stress and inflammatory responses. Food and Function, 5(5), 1027-1037. https://doi.org/10.1039/c3fo60449g
Ma, L., Dong, W., Wang, R., Li, Y., Xu, B., Zhang, J., ... & Wang, Y. (2015). Effect of caloric restriction on the SIRT1/mTOR signaling pathways in senile mice. Brain Research Bulletin, 116, 67-72.
Mahmoud, M. F., ElAshry, F. E. Z. Z., ElMaraghy, N. N., &Fahmy, A. (2017). Studies on the antidiabetic activities of Momordica charantia fruit juice in streptozotocin-induced diabetic rats. Pharmaceutical Biology, 55(1), 758-765. https://doi.org/10.1080/13880209.2016.1275026
Manabe, M., Takenaka, R., Nakasa, T., & Okinaka, O. (2003). Induction of anti-inflammatory responses by dietary Momordica charantia L.(bitter gourd). Bioscience, Biotechnology, and Biochemistry, 67(12), 2512-2517.
Manel, N., Unutmaz, D., &Littman, D. R. (2008). The differentiation of human TH-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORγt. Nature Immunology, 9(6), 641. https://doi.org/10.1038/ni.1610
Marek, A., Brodzicki, J., Liberek, A., &Korzon, M. (2002). TGFb (transforming growth factor) in chronic inflammatory conditions - a new diagnostic and prognostic marker. Med Sci Monit, 8(7), 145-151.
Mazmanian, S. K., Cui, H. L., Tzianabos, A. O., &Kasper, D. L. (2005). An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell ,122(1), 107-118. https://doi.org/10.1016/j.cell.2005.05.007
McRorie Jr, J. W., & McKeown, N. M. (2017). Understanding the physics of functional fibers in the gastrointestinal tract: an evidence-based approach to resolving enduring misconceptions about insoluble and soluble fiber. Journal of The Academy of Nutrition and Dietetics, 117(2), 251-264.
Melgar, S., Karlsson, A., &Michaëlsson, E. (2005). Acute colitis induced by dextran sulfate sodium progresses to chronicity in C57BL/6 but not in BALB/c mice: correlation between symptoms and inflammation. American Journal of Physiology-Gastrointestinal and Liver Physiology, 288(6), G1328-G1338. https://doi.org/10.1152/ajpgi.00467.2004
Miles, J. P., Zou, J., Kumar, M. V., Pellizzon, M., Ulman, E., Ricci, M., …Chassaing, B. (2017). Supplementation of Low- and High-fat Diets with Fermentable Fiber Exacerbates Severity of DSS-induced Acute Colitis. Inflammatory Bowel Diseases, 23(7), 1133-1143. https://doi.org/10.1097/MIB.0000000000001155
Monteleone, I., Sarra, M., Pallone, F., &Monteleone, G. (2012). Th17-related cytokines in inflammatory bowel diseases: friends or foes? Current Molecular Medicine, 12(5), 592-597. https://doi.org/10.2174/156652412800620066
Nerurkar, P.V., Johns, L. M., Buesa, L. M., Kipyakwai, G., Volper, E., Sato, R., …Nerurkar, V. R. (2011). Momordica charantia (bitter melon) attenuates high-fat diet-associated oxidative stress and neuroinflammation. Journal of Neuroinflammation, 8(1), 64. https://doi.org/10.1186/1742-2094-8-64
Neuman M. (2017) Immune dysfunction in inflammatory bowel disease. Translational Research, 149(4), 173-186. https://doi.org/10.1016/j.trsl.2006.11.009
Neurath, M. F., Fuss, I., Kelsall, B. L., Stüber, E., Strober, W., &Stuber, E. (1995). Antibodies to interleukin 12 abrogate established experimental colitis in mice. The Journal of Experimental Medicine, 182(5), 1281-1290. https://doi.org/10.1084/jem.182.5.1281
Ng, S. C., Tang, W., Ching, J. Y., Wong, M., Chow, C. M., Hui, A. J., …Chan, F. K. L. (2013). Incidence and phenotype of inflammatory bowel disease based on results from the Asia-Pacific Crohn’s and colitis epidemiology study. Gastroenterology, 145(1), 158-165. https://doi.org/10.1053/j.gastro.2013.04.007
Nguyen, D., &Xu, T. (2008). The expanding role of mouse genetics for understanding human biology and disease. Disease Models and Mechanisms, 1(1), 56-66. https://doi.org/10.1242/dmm.000232
Oikonomopoulos, A., K van Deen, W., & W Hommes, D. (2013). Anti-TNF antibodies in inflammatory bowel disease: do we finally know how it works?. Current Drug Targets, 14(12), 1421-1432.
Okayasu, I., Hatakeyama, S., Yamada, M., Ohkusa, T., Inagaki, Y., &Nakaya, R. (1990). A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology, 98(3), 694-702. https://doi.org/10.1016/0016-5085(90)90290-H
Örtqvist, A. K., Lundholm, C., Halfvarson, J., Ludvigsson, J. F., & Almqvist, C. (2019). Fetal and early life antibiotics exposure and very early onset inflammatory bowel disease: a population-based study. Gut, 68(2), 218-225.
Padmashree, A., Sharma, G. K., Semwal, A. D., &Bawa, A. S. (2011). Studies on the antioxygenic activity of bitter gourd (Momordica charantia) and its fractions using various in vitro models. Journal of the Science of Food and Agriculture, 91(4), 776-782. https://doi.org/10.1002/jsfa.4251
Patel, S., Patel, T., Parmar, K., Bhatt, Y., Patel, Y., &Patel, N. M. (2010). Isolation, characterization and antimicrobial activity of charantin from Momordica Charantia Linn. fruit. International Journal of Drug Development and Research, 2(3), 0975-9344. https://doi.org/10.1016/j.gie.2007.06.009
Perše, M., &Cerar, A. (2012). Dextran sodium sulphate colitis mouse model: Traps and tricks. Journal of Biomedicine and Biotechnology. https://doi.org/10.1155/2012/718617
Piccirillo, C. A., Letterio, J. J., Thornton, A. M., McHugh, R. S., Mamura, M., Mizuhara, H., &Shevach, E. M. (2002). CD4 + CD25 + Regulatory T Cells Can Mediate Suppressor Function in the Absence of Transforming Growth Factor β1 Production and Responsiveness. The Journal of Experimental Medicine, 196(2), 237-246. https://doi.org/10.1084/jem.20020590
Picornell, Y., Mei, L., Taylor, K., Yang, H., Targan, S. R., &Rotter, J. I. (2007). TNFSF15 is an ethnic-specific IBD gene. Inflammatory Bowel Diseases, 13(11), 1333-1338. https://doi.org/10.1002/ibd.20223
Poritz, L. S., Garver, K. I., Green, C., Fitzpatrick, L., Ruggiero, F., &Koltun, W. A. (2007). Loss of the Tight Junction Protein ZO-1 in Dextran Sulfate Sodium Induced Colitis. Journal of Surgical Research, 140(1), 12-19. https://doi.org/10.1016/j.jss.2006.07.050
Puri, M., Kaur, I., Kanwar, R., Gupta, R., Chauhan, A., &Kanwar, J. (2009). Ribosome Inactivating Proteins (RIPs) from Momordica charantia for Anti Viral Therapy. Current Molecular Medicine, 9(9), 1080-1094. https://doi.org/10.2174/156652409789839071
Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., …Wang, J. (2012). A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 490(7418), 55. https://doi.org/10.1038/nature11450
Raish, M. (2017). Momordica charantia polysaccharides ameliorate oxidative stress, hyperlipidemia, inflammation, and apoptosis during myocardial infarction by inhibiting the NF-κB signaling pathway. International Journal of Biological Macromolecules, 97, 544-551. https://doi.org/10.1016/j.ijbiomac.2017.01.074
Raish, M., Ahmad, A., Ansari, M. A., Alkharfy, K. M., Aljenoobi, F. I., Jan, B. L., …Ali, N. (2018). Momordica charantia polysaccharides ameliorate oxidative stress, inflammation, and apoptosis in ethanol-induced gastritis in mucosa through NF-kB signaling pathway inhibition. International Journal of Biological Macromolecules, 111, 193-199. https://doi.org/10.1016/j.ijbiomac.2018.01.008
Raman, A., &Lau, C. (1996). Anti-diabetic properties and phytochemistry of Momordica charantia L. (Cucurbitaceae). Phytomedicine, 2(4), 349-362. https://doi.org/10.1016/S0944-7113(96)80080-8
Raza, H., Ahmed, I., John, A., &Sharma, A. K. (2000). Modulation of xenobiotic metabolism and oxidative stress in chronic streptozotocin-induced diabetic rats fed withMomordica charantia fruit extract. Journal of Biochemical and Molecular Toxicology, 14(3), 131-139.
Renna, S., Cottone, M., & Orlando, A. (2014). Optimization of the treatment with immunosuppressants and biologics in inflammatory bowel disease. World Journal of Gastroenterology: WJG, 20(29), 9675.
Rosales, C. (2018). Neutrophil: a cell with many roles in inflammation or several cell types?. Frontiers in Physiology, 9, 113.
Ruan, Q., &Chen, Y. H. (2012). Nuclear factor-κB in immunity and inflammation: The Treg and Th17 connection. In Current topics in innate immunity II (pp. 207-221). Springer, New York. https://doi.org/10.1007/978-1-4614-0106-3_12
Ryz, N. R., Patterson, S. J., Zhang, Y., Ma, C., Huang, T., Bhinder, G., ... & Dutz, J. P. (2012). Active vitamin D (1, 25-dihydroxyvitamin D3) increases host susceptibility to Citrobacter rodentium by suppressing mucosal Th17 responses. American Journal of Physiology-Gastrointestinal and Liver Physiology, 303(12), G1299-G1311.
Saeed, S., &Tariq, P. (2005). Antibacterial activities of Mentha piperita, Pisum sativum and Momordica charantia. Pakistan Journal of Botany, 37(4), 997–1001. https://doi.org/doi:10.1016/j.arabjc.2011.01.019
Sharma, S., Sharma, M. C., &Kohli, D.V. (2010). Wound healing activity of the Ether-Chloroform extract of momordica charantia fruits s in rats. Digest Journal of Nanomaterials and Biostructures, 5, 123-126.
Shoaf, K., Mulvey, G. L., Armstrong, G. D., & Hutkins, R. W. (2006). Prebiotic galactooligosaccharides reduce adherence of enteropathogenic Escherichia coli to tissue culture cells. Infection and Immunity, 74(12), 6920-6928.
Sarkar N., Mukherjee A., Barik A. (2013). Olfactory responses of Epilachna dodecastigma (Coleoptera: Coccinellidae) to long-chain fatty acids from Momordica charantia leaves. Arthropod-Plant Interact, 7(3), 339-348. doi: 10.1007/s11829-013-9249-0.
Silva, F. A. R., Rodrigues, B. L., Ayrizono, M. D. L. S., &Leal, R. F. (2016). The Immunological Basis of Inflammatory Bowel Disease. Gastroenterology Research and Practice, 2016. https://doi.org/10.1155/2016/2097274
Skonieczna-Żydecka, K., Marlicz, W., Misera, A., Koulaouzidis, A., &Łoniewski, I. (2018). Microbiome—The Missing Link in the Gut-Brain Axis: Focus on Its Role in Gastrointestinal and Mental Health. Journal of Clinical Medicine, 7(12), 521. https://doi.org/10.3390/jcm7120521
Slavin, J. L. (2008). Position of the American Dietetic Association: health implications of dietary fiber. Journal of the American Dietetic Association, 108(10), 1716-1731.
Stallmach, A., Hagel, S., & Bruns, T. (2010). Adverse effects of biologics used for treating IBD. Best Practice & Research Clinical Gastroenterology, 24(2), 167-182.
Stallhofer, J., Friedrich, M., Konrad-Zerna, A., Wetzke, M., Lohse, P., Glas, J., …Brand, S. (2015). Lipocalin-2 Is a Disease Activity Marker in Inflammatory Bowel Disease Regulated by IL-17A, IL-22, and TNF-α and Modulated by IL23R Genotype Status. Inflammatory Bowel Diseases, 21(10), 2327-2340. https://doi.org/10.1097/MIB.0000000000000515
Stevceva, L., Pavli, P., Husband, A. J., &Doe, W. F. (2001). The inflammatory infiltrate in the acute stage of the dextran sulphate sodium induced colitis: B cell response differs depending on the percentage of DSS used to induce it. BMC Clinical Pathology, 1(1), 3. https://doi.org/10.1186/1472-6890-1-1
Stevens, B. R., Goel, R., Seungbum, K., Richards, E. M., Holbert, R. C., Pepine, C. J., &Raizada, M. K. (2018). Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression. Gut, 67(8), 1555-1557. https://doi.org/10.1136/gutjnl-2017-314759
Su, H.-J., Chiu, Y.-T., Chiu, C.-T., Lin, Y.-C., Wang, C.-Y., Hsieh, J.-Y., &Wei, S.-C. (2018). Inflammatory bowel disease and its treatment in 2018: Global and Taiwanese status updates. Journal of the Formosan Medical Association, 118(7), 1083-1092. https://doi.org/10.1016/j.jfma.2018.07.005
Smids, C., Horjus Talabur Horje, C. S., Drylewicz, J., Roosenboom, B., Groenen, M. J., van Koolwijk, E., ... & Wahab, P. J. (2017). Intestinal T cell profiling in inflammatory bowel disease: linking T cell subsets to disease activity and disease course. Journal of Crohn's and Colitis, 12(4), 465-475.
Sun, X., He, S., Lv, C., Sun, X., Wang, J., Zheng, W., &Wang, D. (2017). Analysis of murine and human Treg subsets in inflammatory bowel disease. Molecular Medicine Reports, 16(3), 2893-2898. https://doi.org/10.3892/mmr.2017.6912
Takahashi, I., Iijima, H., Katashima, R., Itakura, M., &Kiyono, H. (1999). Clonal expansion of CD4+ TCR betabeta+ T cells in TCR alpha-chain- deficient mice by gut-derived antigens. Journal of Immunology, 162(3), 1843-1850.
Takiishi, T., Fenero, C. I. M., &Câmara, N. O. S. (2017). Intestinal barrier and gut microbiota: Shaping our immune responses throughout life. Tissue Barriers, 5(4), e1373208. https://doi.org/10.1080/21688370.2017.1373208
Tan, H. F., &Gan, C. Y. (2016). Polysaccharide with antioxidant, α-amylase inhibitory and ACE inhibitory activities from Momordica charantia. International Journal of Biological Macromolecules, 85, 487-496.. https://doi.org/10.1016/j.ijbiomac.2016.01.023
Tan, M. J., Ye, J. M., Turner, N., Hohnen-Behrens, C., Ke, C. Q., Tang, C. P., …Ye, Y. (2008). Antidiabetic Activities of Triterpenoids Isolated from Bitter Melon Associated with Activation of the AMPK Pathway. Chemistry and Biology, 15(3), 263-273. https://doi.org/10.1016/j.chembiol.2008.01.013
Tanaka, T. (2012). Development of an Inflammation-Associated Colorectal Cancer Model and Its Application for Research on Carcinogenesis and Chemoprevention. International Journal of Inflammation, 2012. https://doi.org/10.1155/2012/658786
Tian, T., Wang, Z., &Zhang, J. (2017). Pathomechanisms of Oxidative Stress in Inflammatory Bowel Disease and Potential Antioxidant Therapies,2017. Oxidative Medicine and Cellular Longevity. https://doi.org/10.1155/2017/4535194
Tilg, H., &Kaser, A. (2011). Gut microbiome, obesity, and metabolic dysfunction. Journal of Clinical Investigation, 121(6), 2126-2132. https://doi.org/10.1172/JCI58109
Torres, J., Burisch, J., Riddle, M., Dubinsky, M., &Colombel, J. F. (2016). Preclinical disease and preventive strategies in IBD: perspectives, challenges and opportunities. Gut, 65(7), 1061-1069. https://doi.org/10.1136/gutjnl-2016-311785
Tsai, T. H., Huang, W. C., Ying, H. T., Kuo, Y. H., Shen, C. C., Lin, Y. K., &Tsai, P. J. (2016). Wild Bitter Melon Leaf Extract Inhibits Porphyromonas gingivalis-Induced Inflammation: Identification of Active Compounds through Bioassay-Guided Isolation. Molecules, 21(4), 454. https://doi.org/10.3390/molecules21040454
Yousefi, N., Sotoodehnejadnematalahi, F., Heshmati-Fakhr, N., Sayyah, M., Hoseini, M., Ghassemi, S., ... & Pourbadie, H. G. (2019). Prestimulation of Microglia Through TLR4 Pathway Promotes Interferon Beta Expression in a Rat Model of Alzheimer’s Disease. Journal of Molecular Neuroscience, 67(4), 495-503. https://doi.org/ 10.1007/s12031-018-1249-1
Vendrame, F., Santangelo, C., Misasi, R., Dionisi, S., Gizzi, C., Realacci, M., …Dotta, F. (2005). Defective lymphocyte caspase-3 expression in type 1 diabetes mellitus. European Journal of Endocrinology,152(1), 119-125. https://doi.org/10.1530/eje.1.01813
Vighi, G., Marcucci, F., Sensi, L., DiCara, G., &Frati, F. (2008). Allergy and the gastrointestinal system. Clinical and Experimental Immunology, 153, 3-6. https://doi.org/10.1111/j.1365-2249.2008.03713.x
Vincken, J. P., Heng, L., deGroot, A., &Gruppen, H. (2007). Saponins, classification and occurrence in the plant kingdom. Phytochemistry, 68(3), 275-297. https://doi.org/10.1016/j.phytochem.2006.10.008
Wadwa, M., Klopfleisch, R., Adamczyk, A., Frede, A., Pastille, E., Mahnke, K., …Westendorf, A. M. (2016). IL-10 downregulates CXCR3 expression on Th1 cells and interferes with their migration to intestinal inflammatory sites. Mucosal Immunology, 9(5), 1263. https://doi.org/10.1038/mi.2015.132
Wallace, K. L. (2014). Immunopathology of inflammatory bowel disease. World Journal of Gastroenterology, 20(1), 6. https://doi.org/10.3748/wjg.v20.i1.6
Wang, L. H., Yang, Y. J., Cheng, W. C., Wang, W. M., Lin, S. H., &Shieh, C. C. (2016). Higher Risk for Hematological Malignancies in Inflammatory Bowel Disease: A Nationwide Population-based Study in Taiwan. American Journal of Gastroenterology, 111(9), 1313. https://doi.org/10.1038/ajg.2016.239
Waterston, R. H., Lindblad-Toh, K., Birney, E., Rogers, J., Abril, J. F., Agarwal, P., …Lander, E. S. (2002). Initial sequencing and comparative analysis of the mouse genome. Nature,420(6915), 520. https://doi.org/10.1038/nature01262
Wei, S.-C., Chang, T.-A., Chao, T.-H., Chen, J.-S., Chou, J.-W., Chou, Y.-H., …Wong, J.-M. (2017). Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease. Intestinal Research, 15(3), 266. https://doi.org/10.5217/ir.2017.15.3.266
Wei, S. C., Lin, M. H., Tung, C. C., Weng, M. T., Kuo, J. S., Shieh, M. J., …Chen, P. C. (2013). A nationwide population-based study of the inflammatory bowel diseases between 1998 and 2008 in Taiwan. BMC Gastroenterology, 13(1), 166. https://doi.org/10.1186/1471-230X-13-166
Wéra, O., Lancellotti, P., & Oury, C. (2016). The dual role of neutrophils in inflammatory bowel diseases. Journal of Clinical Medicine, 5(12), 118.
Winkler, J., Butler, R., & Symonds, E. (2007). Fructo-oligosaccharide reduces inflammation in a dextran sodium sulphate mouse model of colitis. Digestive Diseases and Sciences, 52(1), 52-58.
Winter, R. W., Collins, E., Cao, B., Carrellas, M., Crowell, A. M., & Korzenik, J. R. (2017). Higher 25‐hydroxyvitamin D levels are associated with greater odds of remission with anti‐tumour necrosis factor‐α medications among patients with inflammatory bowel diseases. Alimentary Pharmacology & Therapeutics, 45(5), 653-659.
Xu, X., Shan, B., Liao, C. H., Xie, J. H., Wen, P. W., &Shi, J. Y. (2015). Anti-diabetic properties of Momordica charantia L. polysaccharide in alloxan-induced diabetic mice. International Journal of Biological Macromolecules 81, 538-543. https://doi.org/10.1016/j.ijbiomac.2015.08.049
Yan, Y., Kolachala, V., Dalmasso, G., Nguyen, H., Laroui, H., Sitaraman, S.V., &Merlin, D. (2009). Temporal and spatial analysis of clinical and molecular parameters in dextran sodium sulfate induced colitis. PLoS ONE, 4(6), e6073. https://doi.org/10.1371/journal.pone.0006073
Yang, F., Wang, D., Li, Y., Sang, L., Zhu, J., Wang, J., ... & Sun, X. (2017). Th1/Th2 balance and Th17/Treg-mediated immunity in relation to murine resistance to dextran sulfate-induced colitis. Journal of Immunology Research, 2017.
Yang, L., Xie, L., Xue, B., Goodwin, P. H., Quan, X., Zheng, C., …Wu, C. (2015). Comparative transcriptome profiling of the early infection of wheat roots by Gaeumannomyces graminis var. Tritici. PLoS ONE, 10(4), e0120691. https://doi.org/10.1371/journal.pone.0120691
Yang, X. O., Nurieva, R., Martinez, G. J., Kang, H. S., Chung, Y., Pappu, B. P., …Dong, C. (2008). Molecular Antagonism and Plasticity of Regulatory and Inflammatory T Cell Programs. Immunity, 29(1), 44-56. https://doi.org/10.1016/j.immuni.2008.05.007
Yu, Y., Zhang, X. H., Ebersole, B., Ribnicky, D., &Wang, Z. Q. (2013). Bitter melon extract attenuating hepatic steatosis may be mediated by FGF21 and AMPK/Sirt1 signaling in mice. Scientific Reports, 3, 3142. https://doi.org/10.1038/srep03142
Zhang, Min, Hettiarachchy, N. S., Horax, R., Chen, P., &Over, K. F. (2009). Effect of maturity stages and drying methods on the retention of selected nutrients and phytochemicals in bittermelon (momordica charantia) Leaf. Journal of Food Science, 74(6), C441-C448. https://doi.org/10.1111/j.1750-3841.2009.01222.x
Zhang, Ming, Sun, K., Wu, Y., Yang, Y., Tso, P., &Wu, Z. (2017). Interactions between Intestinal microbiota and host immune response in inflammatory bowel disease. Frontiers in Immunology, 8, 942. https://doi.org/10.3389/fimmu.2017.00942
Zhou, L., Chong, M. M. W., &Littman, D. R. (2009). Plasticity of CD4+ T Cell Lineage Differentiation. Immunity, 30(5), 646-655. https://doi.org/10.1016/j.immuni.2009.05.001
Zhou, L., Ivanov, I. I., Spolski, R., Min, R., Shenderov, K., Egawa, T., …Littman, D. R. (2007). IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nature Immunology, 8(9), 967. https://doi.org/10.1038/ni1488
Zhou, G. X., & Liu, Z. J. (2017). Potential roles of neutrophils in regulating intestinal mucosal inflammation of inflammatory bowel disease. Journal of Digestive Diseases, 18(9), 495-503.
Zhang H Dai Y Liu Y Wu T Li J Wang X Wang W. (2018). Helicobacter pylori Colonization Protects Against Chronic Experimental Colitis by Regulating Th17/Treg Balance. Inflammatory bowel diseases, 24(7), 1481-1492. https://doi.org/10.1093/ibd/izy107
Zhang L.Y., Wang Y.T., Geng L.J. (2011). Bacteriostatic Activity of Total Saponins fromBalsam Pear (Momordica charantia) against Staphylococcus aureus. J. Microbiol, 1, 012.
Zhang M Sun K Wu Y Yang Y Tso P et. al. (2017). Interactions between Intestinal Microbiota and Host Immune Response in Inflammatory Bowel Disease. Frontiers in Immunology, 8, 942. https://doi.org/10.3389/fimmu.2017.00942