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.