Large-scale submerged fermentation of Antrodia cinnamomea for anti-hepatoma activity

BACKGROUND: Submerged cultivation of Antrodia cinnamomea was carried out for manufacturing the fermentation product with anti-hepatoma activity. The fermentation process was optimized for different parameters at shake flask level to obtain products with high inhibition potency against Hep G2 hepatoma cells. Scale-up of the fermentation process was then achieved from 250 mL shake flask to 5 L, 500 L and 5-ton fermenters. RESULTS: Glucose and malt extract were found to be the best carbon and nitrogen sources, respectively. The initial pH of 5.0 and an operating temperature of 22¢XC were the best for a product with lowest IC50 value. A shorter cultivation time was required when the scale of fermentation increased from 5 L to 5 tons. The reducing sugar and solids contents of the broth filtrate were correlated exponentially with the IC50 of the ethanolic extract of mycelium for hepatoma cells, and the level of ergosterol in the mycelium extract follows the same profile as the increase in Hep G2 cells inhibition. CONCLUSION: When Antrodia cinnamomea is cultured in a 5-ton fermenter, 4 weeks are required for the fermentation product to reach the highest anti-hepatoma activity. The solid and reducing sugar contents of the broth filtrate as well as the ergosterol content in the ethanol extract of mycelium can serve as the marker during fermentation for manufacturing product with anti-hepatoma activity. ? 2008 Society of Chemical Industry.