Panax quinquefolius saponins combined with dual antiplatelet drug therapy alleviate gastric mucosal injury and thrombogenesis through the COX/PG pathway in a rat model of acute myocardial infarction

PLoS One. 2018 Mar 27;13(3):e0194082. doi: 10.1371/journal.pone.0194082. eCollection 2018.

Abstract

Objectives: Previous studies have found that Panax quinquefolius saponins (PQS) combined with dual antiplatelet therapy (DAPT) of aspirin and clopidogrel enhances antithrombotic effects while reducing gastric mucosal injury induced by DAPT. We investigated the effects of the combined drug therapy (PQS+DAPT) through the COX/PG pathways.

Methods: Acute myocardial infarction (AMI) was induced in Wistar rats by ligation of the left anterior descending (LAD) coronary artery, and the animals were randomly divided into Model, DAPT, and PQS+DAPT groups. Rats in the sham group did not undergo artery ligation. They were intragastrically treated for 14 days. Myocardial infarct size; myocardial pathology; platelet aggregation rate, CD62p activation, concentrations of thromboxane B2 (TXB2), 6-keto-PGF1α, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI), the TXB2/6-keto-PGF1α ratio were measured. The ultrastructure of the gastric mucosa was observed by scanning electron microscopy. The expression of PGE2 and 6-keto-PGF1α in gastric mucosa was measured by radioimmunoassay, and levels of COX-1, COX-2, and VEGF in gastric mucosa were assessed using immunohistochemistry.

Results: The addition of Panax quinquefolius saponins (PQS+DAPT) to standard DAPT therapy significantly decreased the myocardial infarct area, degree of myocardial lesions, TXB2 and PAI levels, and the TXB2/6-keto-PGF1α ratio, while increasing 6-keto-PGF1α and t-PA levels and reducing the degree of gastric mucosal injury. Expression of PGE2, 6-keto-PGF1α, COX-2, and VEGF in the gastric mucosa was upregulated in the PQS+DAPT group compared with the standard DAPT group.

Conclusion: PQS increases the degree of DAPT inhibition of myocardial necrosis and antiplatelet effects in AMI rats, as well as reducing damage to the gastric mucosa caused by DAPT. The mechanism may be related to inhibition of TXB2 and PAI activity and elevation of 6-keto-PGF1α and t-PA levels in blood, and may be associated with upregulated expression of COX-2, PGE2, PGI2, and VEGF in gastric tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / metabolism
  • Animals
  • Aspirin / pharmacology
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Clopidogrel
  • Cyclooxygenase 2 / metabolism*
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / metabolism
  • Male
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / metabolism
  • Myocardium / metabolism
  • Panax / chemistry*
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Rats
  • Rats, Wistar
  • Saponins / pharmacology*
  • Thromboxane B2 / metabolism
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / pharmacology
  • Tissue Plasminogen Activator / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Platelet Aggregation Inhibitors
  • Saponins
  • Vascular Endothelial Growth Factor A
  • Thromboxane B2
  • 6-Ketoprostaglandin F1 alpha
  • Clopidogrel
  • Cyclooxygenase 2
  • Tissue Plasminogen Activator
  • Ticlopidine
  • Aspirin

Grants and funding

This work was supported by the National Natural Science Foundation of China (81273933 and 81102722), and International Science and Technology Cooperation Program of China (2014DFG32700). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript