Chaga (Inonotus obliquus (persoon) Pilat) is a mushroom traditionally used as a folk medicine for tumors and stomach ulcers in Russia. Previously, we reported the antioxidant potential of Chaga extracts and seven isolated phenolic ingredients. In the present study, we investigated the protective effects of Chaga extracts and other isolated phenolic ingredients against H(2)O(2)-induced oxidative stress in PC12 cells. Intracellular generation of reactive oxygen species (ROS) leads to oxidative stress and subsequent damage of cellular and nuclear components. Chaga extracts and the phenolic ingredients, 3,4-dihydroxybenzalacetone (DBL) and caffeic acid (CA), effectively suppressed intracellular ROS level in H(2)O(2)-treated cells. The H(2)O(2)-induced cell death was more pronounced, effectively prevented in the cells treated with DBL than in cells treated with CA. In addition, ROS activate various signal transduction pathways including the mitogen-activated protein kinase (MAPK) cascade. Therefore, we examined the potentially beneficial effects of DBL on extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38-MAPK signaling activated by H(2)O(2) stimulation. DBL selectively inhibited the phosphorylation of p38-MAPK, without affecting JNK and ERK.