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Cachexia Ameliorating Effect of Oral Supplement with Fucoxanthin Brown Algae Extract in Colitis-associated Colon Cancer
|Authors: ||Jia-yuan Hu|
|Contributors: ||NTOU:Department of Food Science|
|Issue Date: ||2011-11-25T07:38:08Z
|Abstract: ||大腸直腸癌是一種全球常見的消化道惡性腫瘤，主要發生在西方國家，但最近因國人飲食習慣逐漸西化，導致國人在大腸直腸癌的罹患率上逐年增加。已有文獻發現發炎性腸炎的患者，會大大地增加大腸直腸癌的發生率。發炎性腸炎是一種令人衰弱的疾病而特徵為免疫細胞浸潤和免疫介導破壞胃腸道。許多研究證實，褐藻提取物具有抗氧化和抗發炎的特性，其中的墨角藻黃素最為有效。然而，墨角藻黃素萃取物的抗發炎作用，在發炎性腸炎中還沒有得到證實。本論文一開始先從Sargassum glaucescens萃取墨角藻黃素萃取物 (BAE) ，以脂多醣 LPS誘導老鼠巨噬細胞 RAW 264.7 發生發炎反應為細胞模式。在以 BAE 進行處理，觀察其一氧化氮 (NO)、介白素1β (IL -1β) 和環氧合酶-2 (COX - 2) 的mRNA 表現、腫瘤壞死因子-α (TNF –α) 和介白素6 (IL – 6) 的產生量、核內NF-κB 的表現量，可發現墨角藻黃素萃取物皆可降低發炎反應的物質，並呈現劑量依賴的方式。IBD模式，以雄性C57BL / 6小鼠利用硫酸葡聚醣鈉 (5％ DSS, w/v) 在飲用水連續十四天，會造成腸道萎縮，腸道粘膜水腫和便血，並計算其疾病活動指數 (DAI)。在連續七天 5% DSS飲水後，以管餵 BAE 七天，可發現腸道萎縮的情形改善、死亡率下降、疾病指數下降、腸道內 NO、脂質過氧化和細胞激素的產生量降低。而在結腸炎相關的大腸癌 (CAC) 模式中，以腹腔注射致癌劑 azoxymethane (AOM) ，再以 DSS重複誘導腸道發炎，在實驗過程中每兩天管餵薑黃素與 不同濃度之BAE，結果發現可以減少 CAC 的發生率、腫瘤數目、死亡率、增加脾臟細胞增生、惡病質。這些結果表明，墨角藻黃素萃取物為一個具有抗發炎潛力的物質。|
Colorectal cancer (CRC) is one of the most common gastrointestinal tract malignancies worldwide, principally in the western and westernized countries. Patients with inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn’s colitis, are at increased risk of developing colorectal cancer (CRC). intestinal inflammation (ulcerative colitis and Crohn’s disease) also drastically increases the risk of developing colon cancer and the degree of inflammation correlates with cancer risk. IBD is a widespread and debilitating disease characterized by inflammation and immune cell infiltration and immune- mediated destruction of the gastrointestinal tract. Many studies have confirmed that brown algae extracts have antioxidant and anti-inflammatory properties, especially in fucoxanthin. However, anti-inflammatory effects of fucoxanthin in IBD have not been investigated. This study that we use fucoxanthin brown algae extract (BAE) from Sargassum glaucescens was assessed via inhibitory effect of nitric oxide (NO) production in lipopolysaccharide (LPS) induced RAW 264.7 macrophage cells. Moreover, the release of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and the mRNA expression levels of interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) were reduced by the addition of fucoxanthin in a dose-dependent manner. IBD model was induced by administration of dextran sulfate sodium (DSS) (5% W/V) in drinking water to male C57BL/6 mice for seven consecutive days and estimated disease activity index (DAI). DSS produced shrinkage of colon length and increased the relative colon weight/length ratio accompanied by mucosal edema and bloody stool. In IBD model we were oral administration of BAE for seven consecutive days after DSS challenge. In the colitis-associated colorectal cancer (CAC) model, mice were treated with DSS for acute colitis and azoxymethane (AOM), BAE was tested in prevention of colitis-associated colorectal cancer in the AOM-DSS model. BAE mitigated the injurious effects of DSS and ameliorated all the altered biochemical parameters. These results suggest that fucoxanthin brown algae extract could possibly have improve injurious effects of DSS and that it may have therapeutic value in the setting of IBD and CAC.
|Appears in Collections:||[食品科學系] 博碩士論文|
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