Mulberry extracts inhibit LDL oxidation, vascular smoothmuscle cell migration and proliferation.

• Main Authors: Hsieh-Hsun, 何協勳
• Other Authors: Chau-Jong Wang
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/50297242974612340685

博士 === 中山醫學大學 === 生化暨生物科技研究所 === 98 === Atherosclerosis, a disease occurring in arteries, is one of the primary causes of heart diseases and is often the cause of death. Previous studies have shown that atherosclerosis is closely r elated to oxidative low-density lipoprotein dk3u3d. The oxidative modification hypothesis proposes that low density lipoprotein (LDL) oxidation and foam cell formation. Mulberry, a local edible fruit of Morus alba L., is used effectively in traditional medicines against fever, hepatic damage, rheumatic arthritis and hypertension. But few studies have investigated in detail the mechanism and effects of the mulberry fruit against atherosclerosis. In recent studies, the oxidative modification of LDL plays a key role in the pathogenesis of atherosclerosis. In this study, we evaluated two extracts, MWEs (mulberry water extracts) and MPEs (mulberry polyphenol-rich extracts ), which exhibited antioxidative ability in vitro. The antioxidative activity of the mulberry extracts on LDL oxidation was defined by relative electrophoretic mobility (REM), fragmentation of Apo B, thiobarbituric acid reaction substances (TBARS), and radical scavenging assay. Our results showed that low doses of MPEs were able to reduce the REM, Apo B fragmentation, and MDA formation in Cu2+-mediacted LDL oxidation model. MWEs and MPEs also had strong ability of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging. Further, we demonstrated that mulberry extracts could inhibit the foam cell formation and inhibit the expression of the macrophages scavenger receptors (CD36, SR-A) expression induced by oxLDL. Mulberry extracts showed strong potency for scavenging radical, and inhibiting the LDL oxidation and foam cell formation. We have demonstrated that the mulberry water extracts (MWEs) can effectively inhibit LDL oxidation and reduce the development of atherosclerosis in cholesterol-fed rabbits, suggesting that these extracts may prevent atherosclerosis by reducing early atherogenesis. The mechanisms by which mulberry extracts reduce the development of atherosclerosis are not yet fully understood. In these experiments, MWEs and MPEs could inhibit the migration and proliferation of ASMCs (A7r5 cells) by down regulation of Ras/PI3K/Akt pathway. MWEs and MPEs caused cell cycle arrest by inducing AMPK activation and attenuating of cyclin D/CDK and p53/Mdm2 complexes. At highly concentration of the extracts, MWEs and MPEs induced apoptosis by down regulation anti-apoptosis proteins strongly.In conclusion, we not only evaluated the strong antioxidative activity of the polyphenol extracts, but also observed MWEs and MPEs can inhibit proliferation and migration of ASMCs by decreace the transcription activity of NF-κB, FAK, small GTPase, and Ras protein, which were facilitated by integrin receptor. Therefore, it is suggested that the mulberry could be a healthy food to prevent individuals from atherosclerosis .