Mulberry leaf extract inhibits vascular smooth muscle cell migration involving a block of small GTPase and Akt/NF-kappaB signals.
Mulberry, the fruit of Morus alba, is commonly used in Chinese medicines because of its many pharmacologic effects. Mulberry leaves contain many phenolic antioxidants that can reduce cardiovascular disease. Atherosclerosis involves proliferation and migration of vascular smooth muscle cell (VSMC). Thus, we investigated the mechanisms by which mulberry leaf extract (MLE) might inhibit migration of VSMC. MLE was rich in polyphenols (44.82%), including gallic acid, protocatechuic acid, catechin, gallocatechin gallate, caffeic acid, epicatechin, rutin, and quercetin. MLE could inhibit the migration of A7r5 cells in a dose- and time-dependent manner. MLE also inhibited the activities of matrix metalloproteinases (MMPs) MMP-2 and MMP-9, protein expressions, and phosphorylation of FAK and Akt, and protein expressions of small guanosine triphosphatases (GTPases: c-Raf, Ras, Rac1, Cdc42, and RhoA) in a dose-dependent manner. NF-kappaB expression was also inhibited by MLE. MLE could effectively inhibit the migration of VSMC by blocking small GTPase and Akt/NF-kappaB signals.
Chan
Kuei-Chuan
KC
Department of Internal Medicine, Chung-Shan Medical University Hospital, School of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
Ho
Hsieh-Hsun
HH
Huang
Chien-Ning
CN
Lin
Ming-Cheng
MC
Chen
Hsiang-Mei
HM
Wang
Chau-Jong
CJ
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000032:analysis; D061965:Matrix Metalloproteinase Inhibitors; D020559:Monomeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D031625:Morus / Q000737:chemistry*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010636:Phenols / Q000032:analysis; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D059808:Polyphenols; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D051057:Proto-Oncogene Proteins c-akt; D020559:Monomeric GTP-Binding Proteins