Berberine blocks inflammasome activation and alleviates diabetic cardiomyopathy via the miR‑18a‑3p/Gsdmd pathway

Int J Mol Med. 2023 Jun;51(6):49. doi: 10.3892/ijmm.2023.5252. Epub 2023 Apr 28.

Abstract

Diabetic cardiomyopathy (DCM) is a cardiovascular disease which has been reported as a major cause of mortality worldwide for several years. Berberine (BBR) is a natural compound extracted from a Chinese herb, with a clinically reported anti‑DCM effect; however, its molecular mechanisms have not yet been fully elucidated. The present study indicated that BBR markedly alleviated DCM by inhibiting IL‑1β secretion and the expression of gasdermin D (Gsdmd) at the post‑transcriptional level. Considering the importance of microRNAs (miRNAs/miRs) in the regulation of the post‑transcriptional process of specific genes, the ability of BBR to upregulate the expression levels of miR‑18a‑3p by activating its promoter (‑1,000/‑500) was examined. Notably, miR‑18a‑3p targeted Gsdmd and abated pyroptosis in high glucose‑treated H9C2 cells. Moreover, miR‑18a‑3p overexpression inhibited Gsdmd expression and improved biomarkers of cardiac function in a rat model of DCM. On the whole, the findings of the present study indicate that BBR alleviates DCM by inhibiting miR‑18a‑3p‑mediated Gsdmd activation; thus, BBR may be considered a potential therapeutic agent for the treatment of DCM.

Keywords: berberine; diabetic cardiomyopathy; gasdermin D; microRNA‑18a‑3p; pyroptosis.

MeSH terms

  • Animals
  • Berberine* / pharmacology
  • Berberine* / therapeutic use
  • Diabetes Mellitus*
  • Diabetic Cardiomyopathies* / drug therapy
  • Diabetic Cardiomyopathies* / genetics
  • Diabetic Cardiomyopathies* / metabolism
  • Inflammasomes / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / pharmacology
  • Pyroptosis
  • Rats

Substances

  • Berberine
  • Inflammasomes
  • MicroRNAs
  • Gsdmd protein, rat