Neuroprotective Effects of Purpurin Against Ischemic Damage via Anti-inflammatory and MAPK Pathway

Abstract

Purpurin has various effects, including anti-inflammatory effects, and can efficiently cross the blood-brain barrier. In the present study, we investigated the effects of purpurin on oxidative stress in HT22 cells and ischemic damage in the hippocampal CA1 region of gerbils. Oxidative stress induced by H2O2 was significantly ameliorated by treatment with purpurin, based on changes in cell death, DNA fragmentation, formation of reactive oxygen species, and apoptosis (Bcl-2)/antiapoptosis (Bax)-related protein levels. In addition, treatment with purpurin significantly reduced the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK), and p38 signaling in HT22 cells. Transient forebrain ischemia in gerbils led to a significant increase in locomotor activity 1 day after ischemia and significant decrease in number of surviving cells in the CA1 region 4 days after ischemia. Administration of purpurin reduced the travel distance 1 day after ischemia and increased the number of NeuN-immunoreactive neurons in the hippocampal CA1 region of the dentate gyrus 4 days after ischemia. Purpurin treatment significantly decreased microglial activation in the hippocampal CA1 region 4 days after ischemia and ameliorated the ischemia-induced increases in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α 6 h after ischemia. In addition, purpurin significantly alleviated the ischemia-induced phosphorylation of JNK, ERK, and p38 in the hippocampus 1 day after ischemia. These results suggest that purpurin has neuroprotective potential to reduce inflammatory processes and the phosphorylation of JNK, ERK, and p38 in the hippocampus.