Cordyceps sinensis decreases TGF-β1 dependent epithelial to mesenchymal transdifferentiation and attenuates renal fibrosis

It has been suggested that the Traditional Chinese herbal preparation Cordyceps sinensis (CS) may have a beneficial effect in renal disease. The aim of this study was to provide a scientific basis for these claims. The effect of CS was examined in the ureteric obstruction (UUO) model of renal fibrosis. Histological and immunohistochemical assessment of renal injury was made at day 7. In vitro assessment were made by examining the effect of the crude preparation, and characterised fractions of CS, using the tubular epithelial cell line HK-2. Pre-treatment of mice with CS led to a significant attenuation of UUO mediated renal fibrosis. This was associated with abrogation of disease-associated induction of α-smooth muscle actin (α-SMA) and inhibition of E-cadherin expression. The active component of CS resides in a soluble polysaccharide component (Cp-F1) of the crude extract. Cp-F1 antagonises the effects of TGF-β1 on HK-2 cells, preventing induction of fibronectin and α-SMA, and inhibition of the epithelial cell marker E-cadherin. Furthermore Cp-F1 inhibits TGF-β1 dependent activation of a Smad signalling and suppresses the expression of TGF-β receptor mRNA and protein. In summary the data provide in vivo data supporting an anti-fibrotic effect of CS in renal fibrosis. Furthermore the data provide in vitro evidence that this effect is mediated by a large soluble polysaccharide aggregate fraction of CS, which antagonises the effects of TGF-β1 by regulating the expression of its receptor, thus blunting the effect of this cytokine in driving epithelial injury which initiates a pro-fibrotic response.