Astragaloside IV protects rat gastric mucosa against aspirin-induced damage

Int Immunopharmacol. 2016 Dec:41:47-55. doi: 10.1016/j.intimp.2016.10.018. Epub 2016 Nov 2.

Abstract

Aspirin (Asp) is commonly used as an anti-inflammatory drug, but the long-term usage of Asp can lead to severe gastrointestinal damage. Thus the co-administering of Asp with another drug that can suppress its side effect while having no impact on its anti-inflammatory activity would be ideal. Astragaloside IV (AST-IV) is a natural anti-inflammatory compound that has been shown to protect rat gastric mucosa from anhydrous ethanol-inflicted damage. In this study, we investigated whether AST-IV could protect rat gastric mucosa against Asp-induced gastric mucosal damage. Wistar rats administered 150mg/kg Asp showed significant damage to the gastric mucosa, as revealed by gastric damage score and histological evaluation. However, this was largely abolished by co-administering Asp and 25mg/kg or 50mg/kg AST-IV. The protective mechanism of AST-IV involved the suppression of Asp-induced inhibition of cycloxygenase-1 (COX-1) expression, prostaglandin E2 (PGE2) production, superoxide dismutase (SOD) activity and nitric oxide (NO) production. AST-IV blocked Asp-induced inhibition of SOD activity through preventing Asp from inhibiting the expression of SOD-1, both at the mRNA and protein levels. AST-IV did not appear to interfere with the anti-inflammatory activity of Asp since COX-2 level in model gastritis rats treated with Asp plus AST-IV was equally suppressed as in model gastritis rats treated with Asp alone. The results clearly showed that AST-IV could neutralize the toxicity of Asp while having no impact on its anti-inflammatory activity. AST-IV could therefore be considered as a potential drug for relieving the side effect associated with the long-term usage of Asp.

Keywords: Aspirin; Astragaloside IV; Gastric mucosal; Protective effect.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal
  • Apoptosis / drug effects
  • Aspirin
  • Cell Line
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / blood
  • Female
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Humans
  • Lipopolysaccharides
  • Male
  • Membrane Proteins / metabolism
  • Nitric Oxide / blood
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Rats, Wistar
  • Saponins / pharmacology
  • Saponins / therapeutic use*
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / drug therapy*
  • Stomach Ulcer / metabolism
  • Stomach Ulcer / pathology
  • Superoxide Dismutase / blood
  • Superoxide Dismutase / metabolism
  • Triterpenes / pharmacology
  • Triterpenes / therapeutic use*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Lipopolysaccharides
  • Membrane Proteins
  • Protective Agents
  • Saponins
  • Triterpenes
  • Nitric Oxide
  • astragaloside A
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Ptgs1 protein, rat
  • Ptgs2 protein, rat
  • Superoxide Dismutase
  • Dinoprostone
  • Aspirin