Ergosterol Is the Active Compound of Cultured Mycelium Cordyceps sinensis on Antiliver Fibrosis

Cultured mycelium Cordyceps sinensis (CMCS) is a Chinese herbal medicine, which is widely used for a variety of diseases including liver injury in clinic. The current study aims to investigate the protective effects of CMCS against liver fibrosis and to exploit its active antifibrotic substances in vivo and in vitro. For evaluating the antifibrotic effect of CMCS and ergosterol, male C57BL/6 mice were injected intraperitoneally with carbon tetrachloride (CCl(4)) and treated with CMCS (120 mg/kg/d) or ergosterol (50 mg/kg/d). Four weeks later, serum liver function, hepatic hydroxyproline (Hyp) content, liver inflammation, collagen deposition, and expression of alpha smooth muscle actin (α-SMA) in liver tissue were evaluated. Besides, toxicological effects of active compounds of CMCS on hepatocytes and hepatic stellate cells (HSCs) were detected and expressions of permeability of the lysosomal membrane, EdU, F-actin, and α-SMA of activated HSCs were analyzed to screen the antifibrotic substance in CMCS in vitro. Our results showed that CMCS could significantly alleviate levels of serum liver functions, attenuate hepatic inflammation, decrease collagen deposition, and relieve levels of α-SMA in liver, respectively. Ergosterol, the active compound in CMCS that was detected by HPLC, played a dose-dependent inhibition role on activated HSCs via upregulating expressions of permeability of the lysosomal membrane and downregulating levels of EdU, F-actin, and α-SMA on activated HSCs in vitro. Moreover, ergosterol revealed the antifibrotic effect alike in vivo. In conclusion, CMCS is effective in alleviating liver fibrosis induced by CCl(4) and ergosterol might be the efficacious antifibrotic substance in CMCS in vivo and in vitro.