中國橄欖萃取物減緩葡聚醣硫酸鈉誘導小鼠潰瘍性結腸炎之功效

Abstract

發炎性腸道疾病 (inflammatory bowel disease, IBD) 近年來在亞洲的發生率及盛行率有逐年上升的趨勢，但造成此疾病之確切原因仍然不明。目前的治療藥物主要目標為控制腸道之發炎反應與症狀，但長期服用這些抗發炎藥物或生物製劑可能會對病患造成嚴重的副作用。因此，開發新穎、有效且副作用少的天然療法就顯得非常重要。我們過去的研究發現，中國橄欖 (Canarium album L.) 果實甲醇萃取物中的乙酸乙酯區分層 (簡稱COE) 具有抑制腫瘤生長與抗發炎的效果，本論文進一步探討 COE 對葡聚醣硫酸鈉 (dextran sulfate sodium, DSS) 誘導小鼠之潰瘍性結腸炎 (ulcerative colitis, UC) 的改善作用，以評估其緩解發炎性腸道疾病的功效。動物實驗結果顯示，COE 改善了腸炎小鼠體重下降、腸道縮短與疾病活動指數 (disease activity index, DAI) 上升的現象，並有效減少了結腸組織中免疫細胞的浸潤，與上皮組織的損傷程度。COE 也降低了小鼠結腸組織中促發炎細胞激素如介白素-6 (interleukin-6, IL-6) 的 mRNA 表現量與環氧合酶-2 (cyclooxygenase-2, COX-2) 的蛋白質含量；並減少小鼠近端結腸組織中 ICAM-1 (intercellular adhesion molecule-1) 與 Selectin-E 等黏附分子的 mRNA 與蛋白質表現量。而且，COE 也顯著地抑制了人類單核球細胞 THP-1 於人類結腸癌上皮細胞 HCT116 上的附著能力。總的來說，本次研究結果除了證實中國橄欖萃取物 COE 具有緩解 DSS 誘導小鼠之潰瘍性結腸炎之功效，也發現 COE 可以降低發炎性單核球細胞之附著能力，說明了 COE 可作為發炎性腸道疾病的天然療法。

The incidence and prevalence of inflammatory bowel disease (IBD) have been increasing in Asia in recent years, but the underlying causes of this disease are still unclear. Currently, most of the commonly-used treatments for IBD mainly aim to control the inflammation in the gastrointestinal tract, but long-term usage of the anti-inflammatory drugs or biologics could bring critical side effects to the patient. Thus, the exploration of new efficient natural treatment with less side effects is urgently needed. Our previous study has revealed that the methanol-ethyl acetate partitioned fraction from Chinese olive (Canarium album L.) fruit extracts (COE) are able to inhibit tumor growth and also exhibit anti-inflammatory effect. In this study, to evaluate the ameliorating effects of COE on IBD, we investigated the relieving effect of COE on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. The in vivo results indicated that COE treatment reduced weight loss, colon shortening and disease activity index (DAI) in colitis mice. Moreover, histological analysis of colon tissues showed that COE treatment decreased the infiltration level of immune cells and the severity of epithelial damage that caused by DSS. COE treatment also significantly reduced the mRNA expression of pro-inflammatory cytokine interleukin-6 (IL-6) as well as the protein abundance of cyclooxygenase-2 (COX-2). In addition, the mRNA and protein levels of adhesion molecules ICAM-1 (intercellular adhesion molecule-1) and selectin-E in proximal colon tissues were reduced after COE treatment. COE treatment also reduced the adhesion ability of human leukemia monocytic cells THP-1 on human colon cancer cells HCT116. In sum, our results demonstrate that COE ameliorates colonic inflammatory responses in DSS-induced UC in mice and decreases the inflammatory monocyte adhesion in vitro, suggesting the potential of COE as a natural therapeutic for IBD.