25‑OH‑PPD inhibits hypertrophy on diabetic cardiomyopathy via the PI3k/Akt/GSK‑3β signaling pathway
- Xinyu Liu
- Feiran Song
- Chunna Liu
- Yi Zhang
Affiliations: Department of Pharmacology, Jinzhou Medical University, Jinzhou, Liaoning 120001, P.R. China, Department of Gynecology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
- Published online on: June 17, 2020 https://doi.org/10.3892/etm.2020.8893
Copyright: © Liu
et al. This is an open access article distributed under the
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The present study investigated the inhibitory effects and the associated mechanism of the compound 25‑OH‑PPD (PPD) on cardiac hypertrophy, fibrosis and inflammation. The signaling pathways associated with diabetic mellitus cardiomyopathy (DMCM) were investigated using a rat model. DMCM Sprague‑Dawley rats were induced by injection of streptozotocin. The animals were divided into 5 groups as follows: Normal group (NG group), diabetic group, PPD treatment group, PPD/LY294002 group (inhibitor of PI3K/Akt) and PPD/LiCl group [inhibitor of glycogen synthase kinase (GSK) 3β]. The studies were carried out during the 12 weeks following induction of diabetes and the levels of plasma brain natriuretic peptide (BNP), creatine phosphokinase isoenzyme (CK‑MB) were measured. In addition, the volume of myocardial collagen fraction (CVF) was tested. The expression levels of the inflammatory cytokines, including transforming growth factor beta 1 (TGF‑β1), connective tissue growth factor (CTGF), cell adhesion molecules α‑smooth muscle actin (α‑SMA) and vascular adhesion molecule 1 (VCAM‑1) and associated signaling proteins (Akt, GSK‑3β) were measured by biochemical analyses. The levels of BNP and CK‑MB, the volume of CVF, the expression levels of TGF‑β1, CTGF, α‑SMA and VCAM‑1 in the diabetic group were higher compared with those of the normal control group (P<0.05). Conversely, the levels of these molecules were significantly decreased in the PPD treatment groups (P<0.05). The aforementioned effects were partially eliminated in the PPD/LY294002 and PPD/LiCl groups. In addition, PPD treatment significantly increased the expression levels of p‑Akt and decreased the levels of phosphorylated GSK‑3β compared with those of the DMCM group (P<0.05). The data demonstrated that the protective effects of 25‑OH‑PPD against DMCM may be attributed to the PI3k/Akt/GSK‑3β signaling pathway, via the suppression of the α‑SMA/VCAM axis and the downregulation of TGF‑β1 and CTGF expression.