Procyanidin A2 penetrates L-02 cells and protects against tert-butyl hydroperoxide-induced oxidative stress by activating Nrf2 through JNK and p38 phosphorylation

Abstract We examined the protective effects of procyanidin A2 (PA2) against oxidative stress in a human fetal hepatocyte line (L-02), and its mechanism with respect to regulating nuclear factor erythroid 2-related factor 2 (Nrf2), a key factor in the cellular antioxidant response. PA2 protected L-02 cells from oxidative damage that was induced by tert-butyl hydroperoxide, as evidenced by the increase in cell viability and the reduction in lactate dehydrogenase release and intracellular reactive oxygen species production. PA2 promoted the nuclear translocation of Nrf2 and upregulated heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1. In addition, the c-Jun N-terminal kinase and p38 MAP kinase signaling pathways were activated by PA2. PA2 penetrated L-02 cells in dimeric form, with the cytosolic concentration peaking at 24 h, later than the flavan-3-ol monomers. PA2 can be absorbed into plasma and distributed to the liver after oral administration in mice.