Platycodin D and 2"-o-acetyl-polygalacin D2 isolated from Platycodon grandiflorum protect ischemia/reperfusion injury in the gerbil hippocampus

Platycodi radix is used as a folk remedy for several conditions. In this study, we investigated the neuroprotective effects of five major extracts; deapioplatycoside E (DPE), platycoside E (PE), platyconic acid A (PA), platycodin D (PD) and 2"-o-acetyl-polygalacin D2 (PD2) isolated from the P. radix in the hippocampal CA1 region (CA1) 4 or 10 days after ischemia/reperfusion (UR). Each extract was administered into gerbils with intraperitoneal injection (5 mg/kg/day) 10 days before ischemic surgery and the gerbils were sacrificed 4 or 10 days after I/R. Fluorojade B (F-J B, a marker for neurodegeneration) positive ((+)) neurons increased significantly in the stratum pyramidale of the CA1 region in the vehicle-treated group after I/R. A similar pattern was observed in the DPE-, PE- and PA-treated groups; however, in the PD- and PD2-treated groups, F-J B+ neurons were small in number. We also observed that activations of astrocytes and microglia in the CA1 region after I/R were blocked by the PD- and PD2 treatments. In addition, we found that Cu,Zn-superoxide dismutase (SOD1) immuno reactivity in the pyramidal layer of the PD- and PD2-treated groups was similar to that of the sham group and COX-2(+) and NF-kappa B+ cells were significantly lower in the PD- and PD2-treated group than those in the vehicle-treated group after I/R. These results suggest that PD and PD2 rescue neurons in the CA1 region from an ischemic damage. (C) 2009 Elsevier B.V. All rights reserved.