Curcuminoids Attenuate Myocardial Ischemia-Reperfusion Injury by Regulating Total RNA M6a Levels: In Vitro Study

Comb Chem High Throughput Screen. 2023;26(10):1848-1855. doi: 10.2174/1386207325666220929141003.

Abstract

Objective: Myocardial ischemia-reperfusion (IR) injury is an unresolved medical problem with a high incidence. This study aims to analyze the novel molecular mechanism by which curcuminoids protect cardiomyocytes from IR injury.

Methods: A IR model In Vitro of rat cardiomyocytes H9c2 cells was structured. Curcumin (CUR) and its derivatives, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) treated H9c2 cells, and reactive oxygen species (ROS) production, viability, apoptosis, mitochondrial membrane potential (MMP), oxidative stress and total RNA m6A levels of H9c2 cells were detected by using DCFH-DA stain, CCK-8, flow cytometry, Hoechst 33342 stain, TMRM stain, ELISA and RTqPCR. FB23 was used in rescue experiments.

Results: IR significantly increased ROS production, decreased cell viability, and induced apoptosis, MMP loss, and oxidative stress. In addition, IR induced an increase in total RNA m6A levels and changes in m6A-related proteins expression. CUR (10 μM), DMC (10 μM) and BDMC (10 μM), significantly inhibited IR-induced ROS production, apoptosis, MMP loss and oxidative stress, and enhanced cell viability. Furthermore, CUR, DMC and BDMC altered the expression pattern of m6A-related proteins and reduced IR-induced total m6A levels. There was no significant difference in the effects of the three. CUR's protective effect was partially reduced by FB23.

Conclusion: Curcuminoids attenuate myocardial IR injury by regulating total RNA m6A levels.

Keywords: Curcumin; FB23; RNA m6A; bisdemethoxycurcumin; demethoxycurcumin; myocardial ischemia-reperfusion.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Curcumin* / pharmacology
  • Diarylheptanoids / metabolism
  • Diarylheptanoids / pharmacology
  • Myocardial Reperfusion Injury* / drug therapy
  • Myocardial Reperfusion Injury* / metabolism
  • Myocytes, Cardiac / metabolism
  • RNA / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Diarylheptanoids
  • Reactive Oxygen Species
  • Curcumin
  • RNA