Evaluate the Liver Protective Efficacy of Combine Bioactive Compounds of Freshwater Clams and Chlorella pyrenoidosa (I)

View Statistics Email Alert RSS Feed

Information

Details

Project title

Code/計畫編號

NSC98-2321-B022-001

Translated Name/計畫中文名

養殖貝類與綠藻的保健功效與有效成分之研究---綠藻萃取物合併蜆萃取物之保肝功效評估(I)

Funding Organization/主管機關

National Science and Technology Council

Co-Investigator(s)/共同執行人

潘敏雄(計畫主持人)

Department/Unit

Department of Food Science

Website

https://www.grb.gov.tw/search/planDetail?id=1902502

Year

2009

Start date/計畫起

01-08-2009

Expected Completion/計畫迄

31-07-2010

Co-Investigator(s)

Yeuk-Chuen Liu

Bugetid/研究經費

1700千元

ResearchField/研究領域

食品科技(農)
漁業
基礎醫學

許多研究指出纖維化是一種慢性的肝臟病理變化，亦是肝硬化與肝癌形成與發展的重要病症。肝臟病變是相當複雜的症候群，包含了許多細胞的參與與機制調控，然而有許多研究與實驗證實，肝臟中星狀細胞的活化轉型是造成肝臟纖維化的主要原因，活化的星狀細胞並藉由表現促纖維化分子與分泌纖維化膠原蛋白，導致肝臟組織異常的膠原蛋白沉積而導致肝臟的生理功能受損並漸漸發展成肝硬化與肝癌。在目前的臨床研究與治療模式中，皆以抗肝纖維化作為抑制或預防肝硬化與肝癌發展的主要策略，期望藉由以調控纖維化分子的表現、抑制星狀細胞轉型活化或誘導活化型星狀細胞凋亡等不同角度達到預防、降低、減緩或逆轉肝硬化與肝癌的發生，因此也賦予許多抗纖維化試劑在保肝與抗纖維化活性上的研究與開發潛力。台灣地區水產資源豐盛，水產養殖業亦是我國經濟的主要來源，其中蜆與綠藻養殖業甚為活躍，亦帶動許多相關產業的發展；此外蜆的保肝功效於民間流傳甚久，亦有文獻指出綠藻抗病毒與護肝的生理活性；而在我們先前的研究結果中發現，蜆的萃取物具有誘導癌細胞凋亡的能力，亦具有抑制 TGF-β誘發星狀細胞表現促纖維化分子表現的活性，此外在動物實驗中亦發現以餵食的方式給予蜆萃取物，可有效的抑制DMN 誘發大鼠肝臟纖維化的功效；這些研究數據顯示出蜆在調控星狀細胞活化與抑制肝纖維化的高度活性與研究潛力。此外我們分離鑑定出蜆萃取物中的活性成分TNHD 後發現，此活性成分可能來自於蜆濾食之綠藻，或經由濾食後經蜆代謝轉換所產生的生理活性物質；這些研究結果與推論促使我們進一步探討蜆的活性成分TNHD 與綠藻組合的可能功效與機制以及此活性成分的來源與途徑。基於先前的文獻與我們的研究數據，我們擬以三年研究計畫，（一）合成TNHD 並確定抗老鼠肝纖維化的功效。（二）藉由in vitro（TGF-β誘導星狀細胞活化）和 iv vivo（DMN 誘導大鼠肝纖維化）模式探討TNHD 或與綠藻組合的抗老鼠肝纖維化活性與分子機制；（三）並進一步釐清蜆的活性成分TNHD 的來源與途徑及其在生物體內的分布。（四）確定其它綠藻抑制老鼠肝纖維化的活性成分及分子機轉及經蜆攝食後的生物轉換。基於疾病預防與食品保健的立場，希望這些研究能提供飲食攝取蜆與綠藻作為保肝與抗纖維化的科學證據，並提供蜆與綠藻組合產品，於未來開發成為抗纖維化相關之護肝健康食品的評估與參考。 Liver fibrosis is a chronic and progressive disease for development of irreversible liver cirrhosis and cancer. The pathological mechanism of liver disease is very complicated process including different cell types. Previous study reported that the activation and transdifferentiation is the major mechanism of liver fibrosis, which through up-regulation of fibrogenetic mediators and production of ECM component thus result in formation of fibrous scar tissue and dysfunction of liver. The strategies for the prevention and treatment of liver fibrosis including regulate the expression of fibrosis molecules, inhibit the activation of stellate cells or induce the apoptosis of activated-stellate cells. Based on the principles of chemoprevention，targeting the fibrosis should be more beneficial for preventive strategy of progression of liver cirrhosis and cancer. Freshwater clams is the most important cultured clams in Taiwan and also a traditional material exerts liver protective activity. Recently, some studies also suggest Chlorella pyrenoidosa with anti-viral activity and liver protective effect. Our previous studies found that treatment of extract of freshwater clams induced apoptosis in human cancer cells. Furthermore, the extracts of freshwater clam also showed the inhibitory activity on TGF-β -induced HSC activation. In vivo study, treatment with the extracts of freshwater clams also reduces DMN-induced liver fibrosis, by inhibiting the expression of 　α-SMA and accumulation of collagen. These results indicated the strongly efficacy of freshwater clam on targeting fibrosis. Moreover, we also identified the bioactivite compound, TNHD from freshwater clams and with higher inhibitory effect on HSC activation than crude extracts of freshwater clams. However, based on the molecular structure of TNHD, we hypothesize the possible source of TNHD could be biotransformation or bioaccumulation process in freshwater clams. Therefore, these background information and our pervious studies, promote us to investigate the anti-fibrosis efficacy of TNHD and Chlorella pyrenoidosa as well as the molecular mechanisms. Therefore, during the three-year, (一) we will aim to synthesize and evaluate the activities and molecular mechanism of TNHD and Chlorella pyrenoidosa on liver protective activity and anti-liver fibrosis. ( 二) We will use the in vitro (TGF-β-induced activation and transdifferentiation of stellate cells) and in vivo (DMN-induced liver fibrosis) model to examine the liver protective effect and associated molecular mechanisms on dietary administration of TNHD and Chlorella pyrenoidosa. (三) Moreover, identify the distribution and the source of TNHD and Chlorella pyrenoidosa will be further explored during the third year of this proposal. (四) To identify and investigate the anti-fibrosis activities of others bioactive compounds of Chlorella pyrenoidosa and its biotransformation in freshwater clams. We hope could provide the scientific evidence and possible roles of TNHD and Chlorella pyrenoidosa on targeting liver fibrosis improvement and further potential application of TNHD and Chlorella pyrenoidosa as healthy food.

Keyword(s)

蜆
綠藻
星狀細胞
肝纖維化
Freshwater clams
Chlorella pyrenoidosa
stellate cells
liver fibrosis

DSpace CRIS

Evaluate the Liver Protective Efficacy of Combine Bioactive Compounds of Freshwater Clams and Chlorella pyrenoidosa (I)

Details

Description