Therapeutic effect of magnesium lithospermate B on neointimal formation after balloon-induced vascular injury

Kyu Yeon Hur, Hye Jun Seo, Eun Seok Kang, Soo Hyun Kim, Seungjeong Song, Eun Hee Kim, Soyeon Lim, Chulhee Choi, Ji Hoe Heo, Ki Chul Hwang, Chul Woo Ahn, Bong Soo Cha, Mankil Jung, Hyun Chul Lee

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Vascular smooth muscle cell (VSMC) proliferation and migration in response to platelet-derived growth factor (PDGF) play an important role in the development of atherosclerosis and restenosis. Recent evidence indicates that PDGF increases intracellular levels of reactive oxygen species in VSMCs and that both PDGF-induced VSMC proliferation and migration are reactive oxygen species-dependent. Danshen is a representative oriental medicine used for the treatment of vascular disease. Previously, we reported that magnesium lithospermate B, an active component of Danshen, is a potent antioxidant. Thus we investigated the therapeutic potential of magnesium lithospermate B in neointimal formation after carotid artery injury in rats along with its effects on the PDGF signaling pathway for stimulating VSMC proliferation and migration in vitro. PDGF is dimeric glycoprotein composed of two A or two B chains. In this study, we used PDGF-BB, which is one of the isoforms of PDGF (i.e., PDGF-AA, PDGF-BB, and PDGF-AB). Our results demonstrated that magnesium lithospermate B directly scavenged reactive oxygen species in a xanthine/xanthine oxidase system and reduced PDGF-BB-induced intracellular reactive oxygen species generation in VSMCs. In a rat carotid artery balloon injury model, magnesium lithospermate B treatment (10 mg/kg/day, i.p) showed a significant effect on the prevention of neointimal formation compared with vehicle treatment. In cultured VSMCs, magnesium lithospermate B significantly attenuated PDGF-BB-induced cell proliferation and migration as measured by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide (MTT) assay and transwell migration assays, respectively. Further, magnesium lithospermate B inhibited PDGF-BB-induced phosphorylation of phospatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways by scavenging reactive oxygen species. Together, these data indicated that magnesium lithospermate B, a potent reactive oxygen species scavenger, prevented both injury-induced neointimal formation in vivo and PDGF-BB-induced VSMC proliferation and migration in vitro, suggesting that magnesium lithospermate B may be a promising agent to prevent atherosclerosis and restenosis following angioplasty.

Original languageEnglish
Pages (from-to)226-233
Number of pages8
JournalEuropean Journal of Pharmacology
Volume586
Issue number1-3
DOIs
Publication statusPublished - 2008 May 31

Bibliographical note

Funding Information:
We thank Professor Chun Sik Park for his constructive criticism in preparing our manuscript. This work was supported by the Brain Korea 21 Project for Medical Science, Yonsei University. This work was supported by grants from the Oriental Medicine R&D Project, Ministry of Health & Welfare, Republic of Korea (0405-OD00-0815-0013) and from the Department of Internal Medicine, Yonsei University College of Medicine (2005).

All Science Journal Classification (ASJC) codes

  • Pharmacology

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