isorhapontigenin and Infarction--Middle-Cerebral-Artery

Isorhapontigenin (ISO) is one of the main bioactive components of Gnetum cleistostachyum and was shown to possess antioxidant and antitumor functions. Herein, we hope to examine the neuroprotection impacts of ISO in rats subjected to transient middle cerebral artery occlusion/reperfusion (MCAO/R, 2/24 h) injuries. ISO was injected intraperitoneally into the rats immediately after cerebral ischemia. After 24 h of the reperfusion, infarct volume, brain water contents, neurological deficit, and cerebral blood flow were assessed. Hippocampus histopathology change was detected by H&E and TUNEL staining. The expressions of cleaved caspase-3, Bax and Bcl-2, and phospho-Akt (p-Akt) were investigated by real-time RT-PCR or western blot analysis. We found that ISO significantly suppressed the infarct volumes, brain water contents, and neurological deficit, increased CBF, and relieved histopathologic change in a dose-dependent manner. Reduced malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD) and GSH and glutathione peroxidase (GSH-PX) were observed in ISO group. ISO remarkably decreased caspase-3 and Bax and increased levels of Bcl-2. Additionally, ISO upregulated p-Akt expression. Blocking of PI3K activities by wortmannin can abolish the ISO-caused decrease in infarct volumes and neurologic deficit scores and abrogate the promotion of p-Akt. The data indicated that ISO played neuroprotective impacts against focal I/R injuries, possibly related to the activating of PI3K/Akt signaling.

Topics: Animals; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Disease Models, Animal; Hippocampus; Infarction, Middle Cerebral Artery; Male; Neuroprotective Agents; Oxidative Stress; Phosphatidylinositol 3-Kinase; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Stilbenes