25-OH-PPD inhibits hypertrophy on diabetic cardiomyopathy via the PI3k/Akt/GSK-3? signaling pathway.

ABSTRACT: 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) 3?]. 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-?1), connective tissue growth factor (CTGF), cell adhesion molecules ?-smooth muscle actin (?-SMA) and vascular adhesion molecule 1 (VCAM-1) and associated signaling proteins (Akt, GSK-3?) were measured by biochemical analyses. The levels of BNP and CK-MB, the volume of CVF, the expression levels of TGF-?1, CTGF, ?-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-3? 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-3? signaling pathway, via the suppression of the ?-SMA/VCAM axis and the downregulation of TGF-?1 and CTGF expression.

SUBMITTER: Liu X 

PROVIDER: S-EPMC7401478 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature