探討中國橄欖萃取物之生物活性化合物減緩腸道發炎之機制

Abstract

腸道發炎與發炎性腸道疾病 (inflammatory bowel disease, IBD) 密切相關。IBD 是一種腸道慢性、反覆性持續發炎的疾病，會導致腸道組織的損傷、潰瘍、纖維化以及腸道屏障功能的破壞。我們的研究旨在探索治療 IBD 的天然化合物，我們已經證實中國橄欖 (Canarium album L.) 的果實萃取物 (簡稱 COE) 具有抗發炎功效，可抑制促發炎細胞因子、inducible nitric oxide synthase (iNOS) 和 cyclooxygenase-2 (COX-2) 的表達。COE 也能改善 IBD 的發炎狀況，減輕潰瘍性結腸炎 (ulcerative colitis, UC) 小鼠腸道上皮的損傷和免疫細胞的浸潤，並降低結腸組織中細胞黏附蛋白質 intercellular adhesion molecule-1 (ICAM-1) 和 selectin-E 的表達。謝淑貞教授的實驗室鑑定出 COE 中具有抗發炎作用的生物活性化合物，包括沒食子酸 (gallic acid, GA)、鞣花酸 (ellagic acid, EA)、sitoindoside I (SI)、amentoflavone (AMF) 和原兒茶酸 (protocatechuic acid, PA)。本研究進一步探討這五種化合物對腸道屏障功能及免疫反應的調節作用。結果顯示，這五種化合物能降低脂多醣 (lipopolysaccharide, LPS) 誘導的 RAW264.7 小鼠巨噬細胞中之COX-2 和 iNOS 的蛋白質含量，減少促發炎型的 M1 巨噬細胞並增加抗發炎型的 M2 巨噬細胞，還會改善發炎的腸道上皮細胞 CCD841的屏障功能，和降低單核細胞 THP-1 對 CCD841 細胞的附著。總結來說，我們的研究突顯出 COE中生物活性成分的抗發炎潛力，在保護腸道健康方面具有重要意義，並為進一步研究這些化合物的作用機制及其在臨床的應用開啟了新的方向。

Intestinal inflammation is closely associated with inflammatory bowel disease (IBD), a chronic, recurrent condition causing persistent intestinal inflammation, tissue damage, ulceration, fibrosis, and disrupted barrier function. Our research aims to explore natural compounds for the treatment of IBD. We have demonstrated that Chinese olive (Canarium album L.) fruit extract, known as COE, has anti-inflammatory properties. COE inhibits the expression of pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). COE also alleviates inflammation in IBD by reducing epithelial damage and immune cell infiltration in a mouse model of ulcerative colitis (UC), and decreasing intercellular adhesion molecule-1 (ICAM-1) and selectin-E expression in colon tissues. Professor Su-Chen Hsieh's lab has identified the bioactive compounds in COE with anti-inflammatory effects, including gallic acid (GA), ellagic acid (EA), sitoindoside I (SI), amentoflavone (AMF), and protocatechuic acid (PA). This study further investigates the regulatory effects of these compounds on intestinal barrier function and immune response. The results show that these compounds reduce COX-2 and iNOS protein levels in lipopolysaccharide (LPS)-induced RAW264.7 macrophages, decrease pro-inflammatory M1 macrophages, and increase anti-inflammatory M2 macrophages. They also improve the barrier function of the inflamed intestinal epithelial cells, CCD841, and reduce the adhesion of THP-1 monocyte to CCD841 cells. In summary, our study highlights the anti-inflammatory potential of the bioactive components in COE, which shows significant promise for protecting intestinal health, and paves the way for further research on their mechanisms and clinical applications.