Sulfated polysaccharides (SPSs) of Antrodia cinnamomea were extracted by an exhaustive papain digestion and characterized, and their biological functions were evaluated. In this study, we demonstrated the existence of SPSs in the medicinal fungus. A. cinnamomea. Since no SPSs had previously been identified in any fungal organism, we attempted to characterize those from A. cinnamomea. SPSs from A. cinnamomea inhibited in vitro Matrigel tube formation, in an angiogenesis model, in a dose-dependent manner. Furthermore, using serum deprivation-induced apoptosis in neuronal-like PC12 cells as a stress model, the SPSs of A. cinnamomea were effective in preventing serum-deprived apoptosis. Compositional analysis revealed that myo-inositol, fucose, galactose, and glucose were the neutral sugars in SPSs of A. cinnamomea, and these SPSs had a high sulfate content. The sulfation degree paralleled their antiangiogenic and neuroprotective activities. In this work, we report novel data on the structure, antiangiogenic, and neuroprotective effects of these fungal SPSs. (C) 2009 Elsevier Ltd. All rights reserved.