The synergy of diammonium glycyrrhizinate remarkably reduces the toxicity of oxymatrine in ICR mice

Biomed Pharmacother. 2018 Jan:97:19-25. doi: 10.1016/j.biopha.2017.09.039. Epub 2017 Nov 6.

Abstract

Most traditional Chinese medicine prescription dosages are imprecise. This study analyzes the toxicities and adverse effects of a combination the active ingredients of licorice and Kushen medicine: oxymatrine (OMT) and diammonium glycyrrhizinate (DG). The median lethal dose (LD50) and mortality were analyzed in single-dose OMT (or DG) intraperitoneally injected mice with or without combination DG (or OMT). Body weight changes as well as levels of serum sodium and potassium, alanine transaminase (ALT), aspartate transaminase (AST), creatinine, and urea were measured in mice treated with a daily dose of OMT and/or DG for 14days. This study showed that the LD50 of OMT for males and females were 347.44 and 429.15mg/kg, respectively. The LD50 of DG were 525.10 and 997.26mg/kg for males and females, respectively. DG significantly decreased the mice LD50-induced mortality of the OMT, however OMT did not succeed in reducing the LD50-induced mortality rate of DG. The combination of OMT and DG obviously attenuated the changes of the body weight, serum sodium, and potassium induced by DG or OMT alone. These results suggested that toxicity and adverse effects of the OMT was significantly attenuated by DG. The OMT neutralized the adverse effects of the DG, but not the toxicity.

Keywords: Combination; Diammonium glycyrrhizinate; Oxymatrine; Toxicological effect.

MeSH terms

  • Alanine Transaminase / antagonists & inhibitors
  • Alanine Transaminase / blood
  • Alkaloids / administration & dosage*
  • Alkaloids / antagonists & inhibitors
  • Alkaloids / toxicity*
  • Animals
  • Anti-Arrhythmia Agents / administration & dosage
  • Anti-Arrhythmia Agents / toxicity
  • Anti-Inflammatory Agents / administration & dosage*
  • Aspartate Aminotransferases / antagonists & inhibitors
  • Aspartate Aminotransferases / blood
  • Body Weight / drug effects
  • Body Weight / physiology
  • Female
  • Glycyrrhizic Acid / administration & dosage*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mortality / trends
  • Quinolizines / administration & dosage*
  • Quinolizines / antagonists & inhibitors
  • Quinolizines / toxicity*
  • Random Allocation

Substances

  • Alkaloids
  • Anti-Arrhythmia Agents
  • Anti-Inflammatory Agents
  • Quinolizines
  • Glycyrrhizic Acid
  • oxymatrine
  • Aspartate Aminotransferases
  • Alanine Transaminase