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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 
 CARDIOVASCULAR RESEARCH, Vol.87(4) : 713-722, 2010 
Journal Title
Issue Date
Animals ; Antioxidants/pharmacology* ; Apoptosis/drug effects ; Cell Adhesion/drug effects ; Cells, Cultured ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy* ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/physiopathology ; Diabetic Angiopathies/drug therapy* ; Diabetic Angiopathies/etiology ; Diabetic Angiopathies/metabolism ; Diabetic Angiopathies/physiopathology ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology* ; Endothelium, Vascular/drug effects* ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/pathology ; Endothelium, Vascular/physiopathology ; Glucose/metabolism* ; Glycation End Products, Advanced/blood ; Glycosylation ; Heme Oxygenase-1/metabolism ; Humans ; Leukocytes/drug effects ; NF-E2-Related Factor 2/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Nitrites/blood ; Oxidative Stress/drug effects ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Protein Processing, Post-Translational ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Rats, Inbred OLETF ; Rats, Long-Evans ; Reactive Oxygen Species/metabolism ; Time Factors ; Vasodilation/drug effects*
Diabetes ; Endothelial function ; Nitric oxide ; Antioxidant ; Magnesium lithospermate B
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 alpha-lipoic acid (alphaLA), 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 alphaLA 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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Kim, Soo Hyun(김수현)
Ahn, Duk Sun(안덕선) ORCID logo https://orcid.org/0000-0001-9351-6951
Lee, Yong Ho(이용호) ORCID logo https://orcid.org/0000-0002-6219-4942
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
Lee, Hyun Chul(이현철)
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