| Abstract: | 諾麗(noni)，學名為 Morinda citrifolia，含有豐富類黃酮 (flavonoids)、配苷 (glycosides)、維生素、及多元不飽和脂肪酸等，其中以抗氧化成份最為廣泛研究。近幾 年本土栽種 noni 在台南市學甲區至少栽種約 10公頃。 肝纖維化是一個動態、進行性的過程，在某些階段為可逆的，而肝臟星狀細胞的活 化是肝纖維化的成因，其導致的肝硬化是肝癌的高風險因素之一。故如何阻延或逆轉肝 纖維化為預防肝硬化、肝癌的重要課題。 計畫申請人預計花 2年時間，探討諾麗果汁抑制肝纖維化的保健功效及機轉： 第一年將先分析並判定本土自然發酵一年後諾麗果汁中主要的多酚系抗氧化物質 與礦物質含量分析，及探討諾麗果汁萃取物與其主要多酚系成分是否可誘導 HO-1與 STAT1的表現(具抗發炎與抗腫瘤的特性)，建立篩選的平台；再以 TGF-β 或 LPS 來誘 導肝臟星狀細胞株，來探討諾麗果汁萃取物是否具有抑制星狀細胞活化、抗發炎或氧化 壓力的能力，並分析其訊息傳遞途徑例如轉錄因子 NFB、MAPKs (ERK1/2、JNK、p38)、 STAT1、STAT3..等蛋白表現情形，最後探討是否會調控細胞凋亡。 第二年以 TAA誘導肝纖維化的動物模式，探討諾麗果汁是否具有減緩肝纖維化現 象產生，分析肝臟中膠原蛋白與 α-SMA含量、發炎因子表現量或是促纖維化相關因子 的表現量等是否具有相關性，另外也對肝臟抗氧化相關酵素(GSH、CAT、ADH、CYP2E1 與 ALDH)活性、血清生化指標(AST, ALT, ALP, and γ-GTP)做一完整性調查及肝切片中 細胞凋亡程度等。 並依第一年的結果來探討其訊息傳遞途徑是否一致? 計畫申請人預期利用科學方式，明確了解國產諾麗果汁主要的酚系抗氧化物質/含量 與礦物質成分，並藉由一系列動物模式的探討下，提供諾麗果汁所具有的保健功能之依 據。希望能建立一個篩選的模式，來尋找具抗氧化、發炎反應與抑制肝纖維化的天然物。
The bioactive compounds in noni (Morinda citrifolia) juice were indentified as flavonoids, glycosides, vitamins, and polyunsaturated fatty acids. Noni juice (NJ) is also announced to own several health functionalities, especially its antioxidant capacity. Recently, noni originates in southern Taiwan and has been commercially planted about 10 hectares in Syuejia District, Tainan City. The major culprit of liver fibrosis is activation of hepatic stellate cells (HSCs), characterized by transformation from a quiescent phenotype to a proliferative, contractile and secretory phenotype. No clinically efficacious anti-fibrotic drugs and current study is directed to lessening or reversing fibrosis. The first year, we will do a comprehensive investigation of antioxidative phytochemicals and mineral profiles in local noni juice, which is commercially fermented for one year and explore whether noni juice extract and its major polyphenol components can induce HO-1 and STAT1 expression (with anti-inflammatory and anti-tumor properties), the establishment of a platform for screening. Use LPS or TGF- to induce hepatic stellate cell lines to investigate whether noni juice extract has the ability to inhibit the activation of stellate cells, anti-inflammatory or oxidative stress, and analyze their signaling pathways (e.g., NF-B, MAP kinases-ERK/JNK/p38, STAT1, STAT3, HO-1) or apoptotic pathways (caspases 3, 8, or 9). Therefore, in the second year we will investigate the role of protective effect against TAA-induced liver fibrosis. In the animal trial, major analyses will include 1) serum biochemical values, 2) quantitation of hepatic collagens and α-smooth muscle actin (α-SMA), 3) liver function indexes (AST, ALT, ALP, and γ-GTP), 4) oxidative stress: MDA and GSH contents, TEAC levels, and CAT, ADH, CYP2E1, ALDH gene expressions and activities, 5) hepatic gene expression, protein level, or activities of cytokines and enzymes, i.e. COX-2, iNOS, TNF-α, IL-1β, IL-10, KLF-6, TGF-β1, MMPs, and TIMPs, 6) gene and protein levels of apoptosis signals in hepatic cells, 7) levels of hepatic cell death: TUNEL assay, and 8) histological assessments of livers. Via this study, the healthy compounds and effects of NJ on the life-related diseases, i.e. hyperlipidemia and liver damage can be clearly investigated and understood. Meanwhile, the principle investigator hopes that the vital data from this project could be a reference for further NJ studies and also offer scientific evidences for further healthy NJ products; and to set up a screening platform of natural products against liver fibrosis. |
