Stevioside inhibits transforming growth factor-β1-induced cardiac fibroblast differentiation and collagen synthesis by modulation of Smad signaling pathway

Abstract

Stevioside, a low calorie sweetener used in food and beverage, has some beneficial effects. However, the inhibitory effect of stevioside on cardiac fibrosis has not been reported yet. This study aimed to investigate the effect and potential mechanisms in cultured cardiac fibroblasts (CFs). The CFs were stimulated with 10 ng/mL transforming growth factor-β1 (TGF-β1) for 2 h and then incubated with the different concentrations of stevioside for an additional 24 h. The results showed that after treatment of CFs with stevioside, the α-smooth muscle actin, collagen I/III, Smad2/3, P-Smad2/3 and Smad4 expressions were dose-dependently decreased, while the Smad7 expression was increased, especially in the 400 μM group. These findings demonstrated that stevioside could inhibit the differentiation and collagen synthesis in TGF-β1-stimulated CFs, and its mechanisms were associated with the synergic regulatory effects on Smad signaling pathway, including decrease in Smad2/3, P-Smad2/3 and Smad4 expressions and increase in Smad7 expression.