Natural therapeutic magnesium lithospermate B potently protects the endothelium from hyperglycaemia-induced dysfunction

So Hun Kim, Soo Hyun Kim, Minah Choi, Yongho Lee, Young Ook Kim, Duck Sun Ahn, Young Ho Kim, Eun Seok Kang, Eun Jig Lee, Mankil Jung, Jin Won Cho, Darren R. Williams, Hyun Chul Lee

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Aims We have investigated the effects of magnesium lithospermate B (MLB), the active compound of the Oriental herbal remedy, Salvia miltiorrhizae, on endothelial dysfunction associated with diabetes mellitus using cultured endothelial cells and an animal model of type 2 diabetes mellitus. Methods and results The effect of MLB on vasodilatory function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats was assessed. MLB treatment for 20 weeks starting at 12 weeks attenuated the decrease in endothelium-dependent vasodilation in OLETF rats. MLB treatment also increased serum nitrite level and reduced serum advanced glycation end products concentration. The effect of MLB was greater than an equivalent dose of-lipoic acid (LA), a popular antioxidant treatment. MLB rescued the inhibition of endothelial nitric oxide synthase (eNOS) activity and eNOS phosphorylation in endothelial cells cultured in hyperglycaemia. This effect was dependent on Akt phosphorylation and associated with decreased O-linked N-acetylglucosamine protein modification of eNOS. MLB also increased nuclear factor erythroid 2-related factor-2 (Nrf-2) activation in a phosphoinositide 3-kinase/Akt pathway dependent manner. MLB treatment induced the expression of the Nrf-2-regulated antioxidant enzyme, heme oxygenase-1. The antioxidant LA could not produce this effect. Moreover, MLB decreased oxidative stress and endothelial cell apoptosis caused by hyperglycaemia. Conclusion MLB is a naturally occurring, new generation antioxidant that activates eNOS and ameliorates endothelial dysfunction in diabetes by enhancing vasodilation in addition to reducing oxidative stress. The relative strong performance of MLB makes it an ideal candidate for further, expanded trials as a new generation of antioxidant to treat diabetes-related complications.

Original languageEnglish
Pages (from-to)713-722
Number of pages10
JournalCardiovascular Research
Volume87
Issue number4
DOIs
Publication statusPublished - 2010 Sep 1

Bibliographical note

Funding Information:
This work was supported by the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A085136) and a faculty research grant from Yonsei University College of Medicine (6-2008-0172).

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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