Abstract
Aim:
To understand the effects of lithospermic acid (LA), a potent antioxidant from the water-soluble extract of Salvia miltiorrhiza, on the migration and proliferation of rat thoracic aorta vascular smooth muscle cells (VSMCs).
Methods:
VSMC migration, proliferation, DNA synthesis and cell cycle progression were investigated by transwell migration analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, bromodeoxyuridine (BrdU) incorporation assay, and flow cytometric detection, respectively. Intracellular reactive oxygen species (ROS) generation was detected using 2′,7′-dichlorofluorescin diacetate (DCFH-DA). The expression of cyclin D1 protein and matrix metalloproteinase-9 (MMP-9) protein, as well as the phosphorylation state of ERK1/2, were determined using Western blots. The activity of MMP-9 and the expression of MMP-9 mRNA were assessed by gelatin zymography analysis and RT-PCR, respectively.
Results:
LA (25−100 μmol/L) inhibited both lipopolysaccharide (LPS)- and fetal bovine serum (FBS)-induced ROS generation and ERK1/2 phosphorylation. By down-regulating the expression of cyclin D1 and arresting cell cycle progression at the G1 phase, LA inhibited both VSMC proliferation and DNA synthesis as induced by 5% FBS. Furthermore, LA attenuated LPS-induced VSMC migration by inhibiting MMP-9 expression and its enzymatic activity.
Conclusion:
LA is able to inhibit FBS-induced VSMC proliferation and LPS-induced VSMC migration, which suggests that LA may have therapeutic effects in the prevention of atherosclerosis, restenosis and neointimal hyperplasia.
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This work was supported by National Basic Research Program of China (No 2009CB930300)
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Chen, L., Wang, Wy. & Wang, Yp. Inhibitory effects of lithospermic acid on proliferation and migration of rat vascular smooth muscle cells. Acta Pharmacol Sin 30, 1245–1252 (2009). https://doi.org/10.1038/aps.2009.122
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DOI: https://doi.org/10.1038/aps.2009.122
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