Stevioside inhibits lipopolysaccharide-induced epithelial-to-mesenchymal transition of NRK-52E cells by PPARγ activation.

BACKGROUND

Stevioside is a natural diterpenoid compound that possesses anti-inflammatory, immunomodulatory, anti-diabetic, anti-hypertensive, and renal protective effects, but its effect on lipopolysaccharide (LPS)-induced epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells, an important immune pathological mechanism of renal fibrosis, remains unknown. This study employed the renal proximal tubular cells NRK-52E to investigate the effect of stevioside.

METHODS

The LPS-stimulated renal NRK-52E cells were treated with 50, 100, or 200 μM stevioside in the presence or absence of peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9662, the expression levels of intracellular E-cadherin, vimentin, α-smooth muscle actin (α-SMA), PPARγ, nuclear factor kappa B (NF-κB) p65, transforming growth factor-β1 (TGF-β1), signal transducer and activator of transcription 3 (STAT3), p-STAT3, Smad2/3, and p-Smad2/3 proteins were detected by Western blot analysis.

RESULTS

In LPS-stimulated NRK-52E cells, stevioside treatment could reverse the expressions of EMT-related E-cadherin, vimentin, and α-SMA proteins, increase the expression of PPARγ protein, and decrease the expressions of NF-κB p65, TGF-β1, p-STAT3, Smad2/3, and p-Smad2/3 proteins, especially in the 200 μM stevioside-treated group. However, these beneficial effects of stevioside were attenuated or canceled by pretreatment with PPARγ antagonist GW9662.

CONCLUSIONS

Stevioside can inhibit the LPS-induced EMT the reductions of NF-κB, TGF-β1, Smad2/3, p-Smad2/3, and p-STAT3 protein expressions by PPARγ activation in NRK-52E cells, which may provide a pharmacological basis for the potential application of stevioside in the prevention and treatment of renal fibrosis.