ABSTRACT
Ligusticum chuanxiong (LC) and Angelica sinensis (AS) have been widely used as traditional Chinese medicine to treat some pathological settings such as atherosclerosis and hypertension. The aim of this paper is to determine the effects of the extract of LC and AS (ELCAS) on serum-induced vascular smooth muscle cell (VSMC) proliferation, cell cycle and nitric oxide production. The results show that ELCAS significantly inhibited proliferation and protein synthesis of VSMC in a dose and time dependent manner. The cell population assessed by flow cytometry in the G(0)/G(1) phase increased 74% versus 79.8%, concomitant with a decrease in the S phase, 7.4% versus 4.2%, for control versus ELCAS (300 microg/ml). On the other hand, ELCAS significantly increased nitric oxide production of VSMC. The data suggest that ELCAS markedly inhibited VSMC proliferation by arresting G(1) to S progression, which may be associated with nitric oxide production.
Subject(s)
Angelica sinensis/chemistry , Cell Proliferation/drug effects , Drugs, Chinese Herbal/pharmacology , Muscle, Smooth, Vascular/drug effects , Animals , Cell Cycle/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/chemistry , Ligusticum , Male , Muscle, Smooth, Vascular/cytology , Protein Biosynthesis/drug effects , Rats , Rats, WistarABSTRACT
The aim of this study was to determine the effects of ferulic acid on the proliferation and molecular mechanism in cultured vascular smooth muscle cell (VSMC) induced by angiotensin II. It was shown that ferulic acid significantly inhibited angiotensin II-induced VSMC proliferation in a dose-dependent manner. Western blotting analyses suggest that the antiproliferative effect of ferulic acid was involved in the mitogen-activated protein kinases (MAPKs) pathway. While no effect on p38, ferulic acid markedly inactivated the extracellular signal-regulated kinases (ERK1/2) and c-Jun N-terminal kinases (JNK), indicating that the inhibition of ferulic acid on VSMC proliferation was associated with ERK1/2 and JNK rather than p38 pathway. On the expression of cell cycle regulatory proteins, ferulic acid elevated the protein content of p21(waf1/cip1), decreased expression of cyclin D1 and inhibited phosphorylation of retinoblastoma protein, suggesting that ferulic acid inhibited VSMC proliferation by regulating the cell progression from G1 to S phase. The inactivation of MAPKs and modulation of cell cycle proteins of ferulic acid may be of importance in preventing cardiovascular disease.
Subject(s)
Angiotensin II/pharmacology , Cell Proliferation/drug effects , Coumaric Acids/pharmacology , Muscle, Smooth, Vascular/drug effects , Animals , Blotting, Western , Cell Cycle Proteins/metabolism , Cells, Cultured , Cyclin D1/metabolism , Cyclin-Dependent Kinase Inhibitor p21 , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Male , Mitogen-Activated Protein Kinases/metabolism , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/metabolism , Rats , Rats, Wistar , Retinoblastoma Protein/metabolismABSTRACT
Ligusticum chuanxiong and Angelica sinensis have been widely used in traditional Chinese medicine to treat some pathological settings such as atherosclerosis and hypertension. We determined the protective effect of the extract of Ligusticum chuanxiong and Angelica sinensis (ELCAS) on human umbilical vein endothelial cells (ECV304) damage induced by hydrogen peroxide. ECV304 cells were pre-treated with ELCAS and exposed to 5 mM hydrogen peroxide. The results show that ELCAS dose- and time-dependently protected ECV304 cells against hydrogen peroxide damage and suppressed the production of reactive oxygen species (ROS). The decrement of ROS may be associated with increased activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). Western blot analysis revealed that ELCAS significantly increased the phosphorylation of ERK and promoted eNOS expression. These observations indicate that ELCAS protected ECV304 cells against hydrogen peroxide damage by enhancing the antioxidative ability, activating ERK and eNOS signaling pathway. Our data also provide new evidence of Ligusticum chuanxiong and Angelica sinensis in preventing both cardiovascular and cerebrovascular diseases.
