Aloe-emodin ameliorated MI-induced cardiac remodeling in mice via inhibiting TGF-β/SMAD signaling via up-regulating SMAD7

Phytomedicine. 2023 Jun:114:154793. doi: 10.1016/j.phymed.2023.154793. Epub 2023 Mar 30.

Abstract

Background: Aloe-emodin (AE), a natural anthraquinone extract from traditional Chinese medicinal plants, has been certified to protect against acute myocardial ischemia. However, its effect on cardiac remodeling after chronic myocardial infarction (MI) and the possible mechanism remain unclear.

Purpose: This study investigated the effect of AE on cardiac remodeling and oxidative damage induced by myocardial infarction (MI) in vitro and explored the underlying mechanisms.

Methods: Echocardiography and Masson staining were used to demonstrate myocardial dysfunction and fibrosis. Cell apoptosis was detected by TUNEL staining. The expressions of fibrosis-related factors such as type I collagen, α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) were detected by Western blot.

Results: Our data demonstrated that AE treatment significantly improved cardiac function, reduced structural remodeling, and reduced cardiac apoptosis and oxidative stress in mice with myocardial infarction. In vitro, AE could protect neonatal mouse cardiomyocytes (NMCM) from angiotensin II (Ang II)-induced cardiomyocyte hypertrophy and apoptosis, and significantly inhibited (p < 0.05) Ang II-induced reactive oxygen species (ROS) increase. Furthermore, AE treatment significantly reversed the Ang ii-induced upregulation.

Conclusion: In summary, our work reveals for the first time that AE activates the TGF-β signaling pathway by up-regulating Smad7 expression, which in turn regulates the expression of fibrosis-related genes, ultimately improving cardiac function, inhibiting the development of cardiac fibrosis and hypertrophy in rats with chronic MI.

Keywords: Aloe-emodin; Apoptosis; Myocardial infarction; Oxidative stress; SMAD7; TGF-β.

MeSH terms

  • Aloe*
  • Angiotensin II / pharmacology
  • Animals
  • Cardiomyopathies* / metabolism
  • Emodin* / pharmacology
  • Fibrosis
  • Hypertrophy / pathology
  • Mice
  • Myocardial Infarction* / drug therapy
  • Myocardium / metabolism
  • Myocytes, Cardiac
  • Rats
  • Signal Transduction
  • Smad7 Protein / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Ventricular Remodeling

Substances

  • Emodin
  • Transforming Growth Factor beta1
  • Angiotensin II
  • Smad7 protein, rat
  • Smad7 Protein