Wogonin Alleviates Cisplatin-induced Cardiotoxicity in Mice Via Inhibiting Gasdermin D-mediated Pyroptosis

J Cardiovasc Pharmacol. 2021 Jun 16;78(4):597-603. doi: 10.1097/FJC.0000000000001085.

Abstract

Cardiotoxicity has been well documented as a side effect of cisplatin (CDDP) treatment. The inflammatory response plays a crucial role in the pathological process of CDDP-induced cardiotoxicity. Wogonin is a natural flavonoid compound that possesses cardioprotective and anti-inflammatory qualities. Knowledge of the pharmacological effect and mechanism of wogonin could reveal an efficient way to identify therapeutic strategies. In this study, the potential of wogonin to antagonize CDDP-induced cardiotoxicity was evaluated in C57BL/6 mice in vivo and in H9c2 cells in vitro. The results showed that wogonin protected against CDDP-induced cardiac dysfunction, myocardial injury, and pyroptosis in vivo. Using a Gasdermin D expression plasmid, we revealed that wogonin dramatically reduced CDDP-induced pyroptosis by modulating the Gasdermin D protein in H9c2 cells. In conclusion, wogonin has great potential in attenuating CDDP-induced cardiotoxicity. In addition, greater emphasis should be placed on the antipyroptotic effects of wogonin for the treatment of other diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiotoxicity
  • Cell Line
  • Cisplatin
  • Disease Models, Animal
  • Flavanones / pharmacology*
  • Heart Diseases / chemically induced
  • Heart Diseases / metabolism
  • Heart Diseases / pathology
  • Heart Diseases / prevention & control*
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Phosphate-Binding Proteins / antagonists & inhibitors*
  • Phosphate-Binding Proteins / metabolism
  • Pore Forming Cytotoxic Proteins / antagonists & inhibitors*
  • Pore Forming Cytotoxic Proteins / metabolism
  • Protective Agents / pharmacology*
  • Pyroptosis / drug effects*
  • Rats
  • Signal Transduction

Substances

  • Flavanones
  • Gsdmd protein, mouse
  • IL1B protein, human
  • Interleukin-18
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Phosphate-Binding Proteins
  • Pore Forming Cytotoxic Proteins
  • Protective Agents
  • wogonin
  • Cisplatin