Dickkopf-3 upregulation mediates the cardioprotective effects of curcumin on chronic heart failure

Curcumin, isolated from rhizome of turmeric, has been widely studied as a potential therapeutic drug for cancer. However, protective effects of curcumin on chronic heart failure (CHF) have not been fully studied. In the present study, the effects of curcumin on CHF and the underlying mechanisms were investigated. A total of 40 rabbits were randomized into 4 groups: Control rabbits fed with placebo (Con) or curcumin (Con-cur), CHF rabbits fed with placebo (CHF) or curcumin (CHF-cur). CHF was induced by volume and pressure overload. The effects of curcumin on cardiac function and left ventricular (LV) structure were assessed by echocardiography and histology. The effects of curcumin on CHF molecular biomarkers were detected by dihydroethidium and immunohistochemical staining. The effects of curcumin on Dickkopf-related protein 3 (DKK-3), p38 mitogen-activated protein kinase (p38), c-Jun N-terminal kinase (JNK) and apoptosis signal-regulating kinase 1 (ASK1) were assessed by immunohistochemical staining and western blot analysis. Cardiac dysfunction and LV remodeling were successfully produced by ten weeks volume overload and eight weeks pressure overload in the CHF group. Compared with the Con group, the CHF group demonstrated higher levels of CHF molecular biomarkers, a lower level of DKK-3 expression and alterations of p38, JNK and ASK1 protein expression. Curcumin alleviated all those abnormalities markedly in the CHF-cur group. In summary, curcumin may exert cardioprotective effects by up-regulating DKK-3, which in turn may inhibit p38 and JNK signaling pathways in an ASK1-dependent way. The present study demonstrated that Dickkopf-3 upregulation mediates the cardioprotective effects of curcumin on chronic heart failure for the first time.