Cordyceps sinensis: in vitro anti-fibrotic bioactivity of natural and cultured preparations

It has been suggested that the Traditional Chinese herbal preparation Cordyceps sinensis (CS) may have a beneficial effect in renal disease. We have previously demonstrated bio-activity of naturally occurring CS. To satisfy increasing demand, CS derivatives have been produced by aseptic mycelia cultivation. The aim of this work was to compare and contrast the bio-activity of natural CS and two specific products derived from cultured Cordyceps mycelia, “Jinshuibao Capsule” (Paecilomyces sinensis) and “Corbrin Capsule” (Hirsutella sinensis). In addition using two different cell systems we examined the potential anti-fibrotic potential of these products beyond the kidney. All three preparations antagonised the activity of the pro-fibrotic cytokine TGF-β1 in renal epithelial cells. Activity was seen in the raw water-soluble components, and the hydrophilic and hydrophobic extracts from each preparation suggesting that the bio-activity is not confined to one component of the raw material. In addition to the effects in the renal cell line, similar effects of antagonism of phenotypic activation of pulmonary fibroblasts by TGF-β1 was also seen suggesting an applicability of these observations to solid organ fibrosis beyond the kidney. Mechanistically the data demonstrate antagonism of TGF-β1 activation of Smad signalling and specifically of induction of the hyaladherin TSG-6, which we have previously demonstrated to orchestrate the formation of a hyaluronan, peri-cellular coats driving phenotypic cellular activation. In summary the data support the claim that both naturally occurring and products derived from cultured Cordyceps mycelia have similar bio-activity which may have particular relevance for solid organ fibrosis and associated organ dysfunction