Ginkgolide B Protects Cardiomyocytes from Angiotensin II-Induced Hypertrophy via Regulation of Autophagy through SIRT1-FoxO1

Abstract

Ginkgolide B (GB) is an active ingredient extracted from Ginkgo biloba leaves. However, the effects of GB on cardiac hypertrophy remain unclear. The study is aimed at determining whether GB could alleviate cardiac hypertrophy and exploring its underlying molecular mechanism. Rat cardiomyocyte cell line H9c2 cells were pretreated with GB and incubated with angiotensin II (Ang II) to simulate an in vitro cardiac hypertrophy model. Cell viability, cell size, hypertrophy markers, and autophagy were determined in H9c2 cells after Ang II treatment. Proteins involved in autophagy and the SIRT1 pathway were determined by western blot. Our data demonstrated that GB attenuated Ang II-induced cardiac hypertrophy and reduced the mRNA expressions of hypertrophy marker, atrial natriuretic peptide (ANP), and β-myosin heavy chain (β-MHC). GB further increased Ang II-induced autophagy in H9c2 cells and modulated expressions of autophagy-related proteins Beclin1 and P62. Modulation of autophagy using autophagy inhibitor 3-methyladenine (3-MA) could abrogate GB-downregulated transcription of NPPA. We then showed that GB attenuated Ang II-induced oxidative stress and reduction in SIRT1 and FoxO1 protein expression. Finally, the effect of GB on autophagy and cardiac hypertrophy could be reversed by SIRT1 inhibitor EX-527. GB inhibits Ang II-induced cardiac hypertrophy by enhancing autophagy via the SIRT1-FoxO1 signaling pathway and might be a potential agent in treating pathological cardiac hypertrophy.

Garlic oil alleviates high triglyceride levels in alcohol‐exposed rats by inhibiting liver oxidative stress and regulating the intestinal barrier and intestinal flora

“…The results of an in vitro trial suggested that Sirt1/FoxO1 may be one of the potential therapeutic targets for LPS‐induced oxidative stress injury in rat insulinoma cells (Mo et al., 2019 ). The Sirt1/FoxO1 pathway increases the levels of antioxidant enzymes SOD and GSH‐Px and reduces the level of MDA reducing the oxidative stress injury of H9C2 cardiomyocytes (Jiang et al., 2021 ). PGC‐1α is a transcription coactivator that can regulate the stability of oxidants and antioxidants by increasing the expression of superoxide dismutase‐2 and GSH‐Px (Liang et al., 2020 ; Tian et al., 2019 ).…”

Activation of the sirtuin silent information regulator 1 pathway inhibits pathological myocardial remodeling

“…Furthermore, it reduced the levels of expression of SIRT1 and FoxO1. Conversely, addition of a SIRT1 agonist attenuated the Ang II-induced oxidative stress index (Jiang et al, 2021). Fibroblast growth factor 20 (FGF20) is a member of the fibroblast growth factor family and is involved in apoptosis, senescence, inflammation, and autophagy.…”

“…Treatment of rat cardiomyocyte cell lines with Ang II results in insufficient cardiomyocyte autophagy and interferes with the expression of the autophagy-associated proteins beclin1 and p62. Ginkgolide B Protects Cardiomyocytes from Angiotensin II-Induced Hypertrophy via Regulation of Autophagy through SIRT1-FoxO1 (Jiang et al, 2021). Another study showed that SIRT1-dependent deacetylation of the transcription factor Foxo1 is involved in cardiac senescence: SIRT1 activates FoxO1, promoting its nuclear localization, and Akt inhibits it by phosphorylation, preventing nuclear translocation.…”

Sesamin suppresses angiotensin‐II‐enhanced oxidative stress and hypertrophic markers in H9c2 cells

“…Cardiomyocyte hypertrophy is characterized by increased cell surface area. 3,18,19 We determined the cell morphology of H9c2 cells after Ang-II stimulation with or without different concentrations of SA treatment. Quantifying the H9c2 cell area showed a significant increase in the cardiomyocyte area after Ang-II (1 μM) stimulation compared to control cells.…”

“…Persistent myocardial hypertrophy leads to myocardial remodeling and left ventricular dilatation, leading to cardiomyopathy, myocardial fibrosis disease, and ultimately heart failure. [3][4][5] In addition, a previous report suggested that myocardial hypertrophy is characterized by an increase in myocardial cell mass and size caused by the activation of hypertrophic markers.…”