桑椹（mulberry）是一種天然植物桑科落葉喬木”桑”（Morus alba L.）的果實，具有豐富的色素成分，而許多色素的成分已被證實是一種很好的抗氧化物質，如awobanin及許多flavonoids，可能有抑制心血管病變的功能，因此本研究探討（1）桑椹水萃取物（MEs）降血脂及抑制低密度脂蛋白氧化及心血管病變等作用；進一步探討（2）抑制氧化型低密度脂蛋白（ox-LDL）誘導巨噬細胞apoptosis （可能與atherosclerotic pathogenesis 有關）；及（3）探討抑制 aortic smooth muscle cell （ASMC）增生之作用是否與cell cycle arrest 及apoptosis 有關。 第一年之計劃擬探討MEs抑制血脂肪及抗LDL之氧化作用，分別在cell free system 及endothelial cell中以thiobarbituric acid reactive substances （TBARS）及electrophoretic mobility（EM）觀察LDL氧化情形；進一步以老鼠及兔子動物模式誘導之atherosclerosis來確認MEs降血脂及降低ox-LDL形成；由於ox-LDL誘導巨噬細胞apoptosis，可能與atherosclerosis或thrombosis相關，因此第二年的工作我們擬探討MEs是否抑制ox-LDL-induced apoptosis，並研究相關的機轉；第三年的工作，我們擬探討MEs對ASMC細胞抗增生，抑制細胞週期，促進凋謝死亡及相關的分子機轉。 從以上的結果，我們預期MEs有（1）降血脂、抗LDL氧化作用；（2）抑制ox-LDL-induced atherosclerosis是經由anti-apoptosis in macrophage cells；（3）抑制ASMC細胞增生是經由MEs造成cell cycle arrest 及apoptosis。因此，從以上的研究，MEs可發展為一種預防心血管疾病之保健食品。
Mulberry has been reported to contain awobanin and number of flavonoids including gossypetin, hibiscetin and quercetin. In vitro experimental studies have shown that administration of those components produce anti-inflammation, hypotensive and hypocholesterolemic. In spite of the wide use of Mulberry extracts (MEs) in folk medicine for treatment of various diseases, there are no reports in the literature on their anti-atherosclerosis activity. The aim of this study was to evaluate the effects of an aqueous extract obtained from Mulberry extracts (MEs) on the (1) susceptibility of LDL to oxidation and on plasma lipid in rabbits affected by experimental atherosclerosis induced by the intake of high levels of saturated fat and cholesterol; (2) inhibition of ox-LDL-induced apoptosis in cultured macrophages, the mechanisms of anti-apoptosis of MEs in macrophages would be studied to determine whether the apoptotic signals and gene expression are involved; (3) inhibition of proliferation and cell cycle progression and induced cell apoptosis in aortic smooth muscle cells (ASMC). The molecular mechanisms of the anti-proliferative and apoptotic effects of MEs in ASMC would be investigated. The results of the these studies may be used to demonstrate the effects of MEs on the preventive cardiovascular diseases by (1) antilipidemia and inhibit LDL-oxidation; (2)inhibit ox-LDL-induced apoptosis in macrophages; (3) anti-proliferation in ASMC. These results also provide MEs as a health food for preventing cardiovascular disease.
