Curcumin Reduces Cardiac Fibrosis by Inhibiting Myofibroblast Differentiation and Decreasing Transforming Growth Factor β1 and Matrix Metalloproteinase 9/Tissue Inhibitor of Metalloproteinase 1

Objective: To study the effect of curcumin on fibroblasts in rats with cardiac fibrosis. Methods: The rats were randomly divided into 4 groups(n=12 in each group): the normal control, isoproterenol(ISO), ISO combined with low-dose curcumin(ISO+Cur-L), and ISO combined with high-dose curcumin(ISO+Cur-H) groups. ISO+Cur-L and ISO+Cur-H groups were treated with curcumin(150 or 300 mg·kg-1·day-1) for 28 days. The primary culture of rat cardiac fibroblast was processed by trypsin digestion method in vitro. The 3rd to 5th generation were used for experiment. Western blot method was used to test the expression of collagen type Ⅰ/Ⅲ, α-smooth muscle actin(α-SMA), transforming growth factor(TGF)-β1, matrix metalloproteinase(MMP)-9 and tissue inhibitor of metalloproteinase(TIMP)-1. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetr-azolium bromide(MTT) assay was applied to test the proliferation of fibroblast. Result: Curcumin significantly decreased interstitial and perivascular myocardial collagen deposition and cardiac weight index with reducing protein expression of collagen type Ⅰ/Ⅲ in hearts(P<0.05). In addition, curcumin directly inhibited angiotensin(Ang) Ⅱ-induced fibroblast proliferation and collagen type Ⅰ/Ⅲ expression in cardiac fibroblasts(P<0.05). Curcumin also inhibited fibrosis by inhibiting myofibroblast differentiation, decreased TGF-β1, MMP-9 and TIMP-1 expression(P<0.05) but had no effects on Smad3 in Ang Ⅱ incubated cardiac fibroblasts. Conclusions: Curcumin reduces cardiac fibrosis in rats and Ang Ⅱ-induced fibroblast proliferation by inhibiting myofibroblast differentiation, decreasing collagen synthesis and accelerating collagen degradation through reduction of TGF-β1, MMPs/TIMPs. The present findings also provided novel insights into the role of curcumin as an anti-fibrotic agent for the treatment of cardiac fibrosis.