Curcumin suppresses cardiac fibroblasts activities by regulating the proliferation and cell cycle via the inhibition of the p38 MAPK/ERK signaling pathway.

Cardiac fibrosis is a deleterious effect of many cardiovascular diseases. Previous studies have shown that curcumin has exhibited protective effects on cardiovascular diseases. The aim of the present study was to evaluate the effects of curcumin on the activity of human cardiac fibroblasts (CFs) and to elucidate the underlying mechanisms involved. Human CFs were incubated with or without curcumin (20 µmol/l) and transforming growth factor β1 (TGF‑β1; 10 ng/ml), and the expression of α‑smooth muscle actin (α‑SMA), collagen type Iα (COLA)‑1 and COLA3 was evaluated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Cell proliferation was evaluated by Cell Counting Kit‑8 analysis, and phases of the cell cycle were studied by flow cytometry. Western blot analysis was performed to evaluate the expression of cyclin‑dependent kinase 1 (CDK1), Cyclin B, phosphorylation (p)‑mothers against decapentaplegic homolog 2/3 (p‑smad2/3), p‑P38, and p‑extracellular regulated protein kinases (ERK). Curcumin significantly reduced mRNA and protein levels of α‑SMA, COLA1, and COLA3 in CFs stimulated with TGF‑β1. However, in the absence of TGF‑β1, curcumin did not have any effects on CFs, suggesting that curcumin inhibited TGF‑β1‑mediated CF activities, including differentiation and collagen deposition. Additionally, curcumin inhibited the proliferation of TGF‑β1‑treated CFs, and promoted G2/M phase cell cycle arrest. Curcumin reduced cell cycle protein expression by inhibiting smad2/3, p38 mitogen‑activated protein kinase, and ERK phosphorylation in TGF‑β1‑treated CFs. Thus, these results indicated that curcumin may be a potential anti‑fibrotic drug to treat cardiac fibrosis.