Mulberry water extracts inhibit rabbit atherosclerosis through stimulation of vascular smooth muscle cell apoptosis via activating p53 and regulating both intrinsic and extrinsic pathways.
Previous studies have shown that mulberry water extracts (MWEs), which contain polyphenolic compounds, have an antiatherosclerotic effect in rabbits. Apoptosis of vascular smooth muscle cells (VSMCs) is the key determinant of the number of VSMCs in remodeling. To improve the recovery from atherosclerosis pathology, it would be ideal to induce regression of atherosclerotic plaques and apoptosis of VSMCs. In this study, we treated high-cholesterol-diet-fed (HCD-fed) rabbits with MWEs, and we found that the MWEs effectively inhibited HCD-fed-induced intimal hyperplasia of vessel walls. We also found that MWEs initially activate JNK/p38 and p53, which in turn activate both Fas-ligand and mitochondria pathways, thereby causing mitochondria translocation of Bax and the reduction of Bcl-2 that trigger the cleavage of procaspases, finally resulting in apoptosis of VSMCs. In addition, 2.5-5.0 g/day of MWEs for humans may be enough to prevent atherosclerosis.
Department of Internal Medicine, Chung-Shan Medical University Hospital , No. 110, Sec. 1, Jianguo N. Road, Taichung 402, Taiwan.
Kuei-Chuan
KC
Chan
Hsieh-Hsun
HH
Ho
Ming-Cheng
MC
Lin
Cheng-Hsun
CH
Wu
Chien-Ning
CN
Huang
Wen-Chun
WC
Chang
Chau-Jong
CJ
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D049109:Cell Proliferation; D015536:Down-Regulation / Q000187:drug effects; D005638:Fruit / Q000737:chemistry; D006801:Humans; D031625:Morus / Q000737:chemistry*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein