Magnesium lithospermate B reduces myocardial ischemia/reperfusion injury in rats via regulating the inflammation response

Pharm Biol. 2013 Nov;51(11):1355-62. doi: 10.3109/13880209.2013.791324. Epub 2013 Jul 18.

Abstract

Context: Magnesium lithospermate B (MLB), an active polyphenol acid of Danshen [Radix Salviae miltiorrhizae (Labiatae)], showed renoprotective, neuroprotective and myocardial salvage effects. Previous studies demonstrated that MLB could effectively suppress the production of cytokines and their associated signaling pathways in activated human T cells.

Objective: The purpose of this study was to examine the beneficial effects of MLB on myocardial ischemia/reperfusion (MI/R) injury and to explore its potential mechanisms related to anti-inflammation.

Materials and methods: Sprague-Dawley rats were grouped as sham group, model group and MLB-treated (15, 30 and 60 mg/kg) groups. Animals were subjected to MI/R injury by the occlusion of left anterior descending artery for 30 min followed by reperfusion for 3 h. At the end of reperfusion, blood samples were collected to determine the serum levels of cardiac troponin (cTnI), creatine kinase-MB (CK-MB), tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). Hearts were harvested to assess infarct size, histopathological changes and the activity of myeloperoxidase (MPO). The expression of phosphor-IkB-α and phosphor-nuclear factor kappa B (NF-κB) were assayed by western blot.

Results: MLB administration significantly (p < 0.05) reduced: (1) ST-segment elevation (0.23 mv), (2) the infarct size (22.5%), (3) histological scores of myocardial injury (1.67 score), (4) myocardial injury marker enzymes: cTnI (5.64 ng/ml) and CK-MB (49.57 ng/ml) levels, (5) pro-inflammatory cytokines: TNF-α (97.36 pg/ml), IL-1β (93.35 pg/ml) and IL-6 (96.84 pg/ml) levels, (6) MPO activity (1.82 U/mg), (7) phosphor-NF-κB (0.87) and phosphor-IkB-α (0.96) expression.

Discussion and conclusion: Our study provided evidence that MLB ameliorated the inflammatory process associated with MI/R injury via NF-κB inactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Biomarkers / blood
  • Creatine Kinase, MB Form / blood
  • Cytokines / blood
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Electrocardiography
  • I-kappa B Proteins / metabolism
  • Inflammation / blood
  • Inflammation / immunology
  • Inflammation / prevention & control*
  • Inflammation Mediators / blood
  • Male
  • Myocardial Infarction / blood
  • Myocardial Infarction / immunology
  • Myocardial Infarction / pathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / blood
  • Myocardial Reperfusion Injury / immunology
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / immunology
  • Myocardium / metabolism
  • Myocardium / pathology
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • Peroxidase / metabolism
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Time Factors
  • Troponin I / blood

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Cytokines
  • Drugs, Chinese Herbal
  • I-kappa B Proteins
  • Inflammation Mediators
  • NF-kappa B
  • NFKBIA protein, human
  • Nfkbia protein, rat
  • Troponin I
  • lithospermate B
  • NF-KappaB Inhibitor alpha
  • Peroxidase
  • Creatine Kinase, MB Form