第一部份
追尋抗氧化、抗衰老的過程中，科學家發現在一些高等植物中所含之天然化合物，具有抗氧化、抗衰老的作用，藉由抗氧化的作用來抑制LDL的氧化修飾，是一種有效預防動脈粥狀硬化發生的方法。本研究之目的為評估由桑葉所分離出的水萃取物(MLE) 與多酚萃取物(MLPE)，其保護LDL避免被氧化及抑制動脈粥狀硬化發生之效果，而進行體外抗氧化實驗與細胞實驗來驗證。本實驗利用新鮮桑葉為材料，以銅離子誘導LDL氧化的模式進行體外抗氧化實驗，並以LDL氧化時其蛋白部分的氧化修飾反應與脂質部分的過氧化反應作為氧化指標。藉由LDL蛋白表面電荷改變的程度與脂質過氧化產物MDA的生成量減少的結果發現，MLE 與MLPE皆具有抑制LDL被氧化的能力，此外也具有清除DPPH 自由基之作用。而在細胞實驗方面，而在給予低濃度的MLE 或MLPE時，即可有效地減少巨噬細胞轉形為泡沫細胞，這些現象都證明MLE 與MLPE 確實具有減緩動脈硬化的發生過程之能力。由上述體外抗氧化實驗與細胞實驗結果顯示，MLE 與MLPE具有極佳的抗氧化活性並能抑制LDL的氧化，此外也透過抑制清除者接受器CD36與SR-A的表現調控巨噬細胞因吞噬過量的ox-LDL而造成的泡沫細胞之形成，進而達到降低動脈粥狀硬化發生。綜合以上結果，我們認為桑葉萃取物具有預防動脈粥狀硬化的作用，而能應用於保健食品的開發。
第二部份
癌症預防已為世界趨勢，因此尋找特殊化學預防物質為現今之重要工作。有許多報告證實荷葉具抗氧化活性、降血脂等作用，目前尚無有關荷葉對於抗癌方面之研究。所以本研究擬以動物實驗模式深入探討台灣之荷葉萃取物抑制腫瘤生長之功效，並進一步探討其中抑制之機制。利用所萃取之荷葉萃取物(NLE)針對動物誘發性腫瘤試驗做評估，結果顯示荷葉萃取物具有降低乳癌發生率、減少乳癌發生之數目、延緩乳癌發生之時間的效果。接著以MCF-7 細胞為實驗模式，處理在不同劑量NLE下，雖未造成有DNA 斷裂與細胞凋亡的情形，但是卻出現NLE 能夠誘導乳癌細胞使其細胞週期停滯在G0/G1 phase 的現象，而探究其分子機轉後，發現是透過PI3K/Akt路徑，影響脂肪酸合成(FAS)之表現進而造成細胞週期停滯作用。再以動物移植性腫瘤試驗證明，NLE確實能夠抑制腫瘤之生長。從以上結果我們可以提出荷葉萃取物可以預防癌症之發生。由於荷葉在國內易種植，因此本研究成果可應用於發展為降低癌症發生率之健康食品。
Part I
Cardiovascular disease has been a major cause of mortality in human and hyperlipidemia plays an important role contributing to atherosclerosis. Oxidated LDL (ox-LDL) has known to damage the endothelial cells and cause endothelial dysfunction. And ox-LDL-mediated foam cell formation by macrophage initiates the cascade of atherosclerosis. This study was to evaluate the anti-oxidative and anti-atherosclerotic effects of the MLE and MLPE by a model of in vitro antioxdation and cell culture. As shown in previous studies Morus alba L. leaves extract is a nature plant containing a lot of pigments that was found to possess antioxidative activity. In this study, we evaluated the antioxidative activity of the Morus alba L. leaves extract (MLE and MLPE) by measuring their effects on LDL oxidation and anti-atherosclerotic abilities. MLE and MLPE possessed the ability of DPPH radical scavenging. The antioxidative activity of the MLE and MLPE on LDL oxidation was defined by relative electrophoretic mobility (REM) and thiobarbituric acid-relative substances (TBARS) assay. Our results showed that MLE and MLPE were able to reduce REM and inhibit TBARS assay in the Cu2+-mediated oxidative LDL. Taken together, low concentration of MLE and MLPE could reduce marked the cellular cholesterol and triglycerides accumulation in macrophage and inhibit the formation of foam cells. MLE inhibits ox-LDL-induced CD36 and SR-A expression. We found MLE also reduced ox-LDL-mediated ROS increased. MLE reduces macrophage phagocytosis by Dil-acLDL. Our study demonstrates the MLE and MLPE can inhibit the oxidation of LDL and has the anti-oxidatic and anti-atherosclerotic properties.
Part II
Over the pass decade, advances in understanding carcinogenesis have made possible the identification of the candidates of chemopreventive agents that are being developed to hit the key molecular targets. Nuciferine Leaf extract (NLE) has been identified a lot of benefit about anti-oxidant and reduced risks of cardiovascular disease. In this study aimed to define the anti-carcinogenesis and the mechanism of NLE reduced chemical-induced cancer in animal model. First we found that NLE extracted from Nuciferine Leaf suppressed the chemical induced incidence, multiplicity and tumor volume of mammary tumors in rats. Next, we observed that NLE caused the cell cycle arrest in the G0/G1 phase in human breast cancer cell line MCF7. The result also revealed that NLE reduced phosphorylation in Akt and expression of fatty acid synthase (FAS) in NLE-treated MCF7 cells. Finally, murine xenograft model also confirmed that NLE inhibited tumor growth rate and tumor weight. Altogether, the findings of the study reveal that NLE should be used to develop a new chemopreventive agent.
