6'-O-Galloylpaeoniflorin Attenuates Cerebral Ischemia Reperfusion-Induced Neuroinflammation and Oxidative Stress via PI3K/Akt/Nrf2 Activation.

Abstract

6'-O-galloylpaeoniflorin (GPF), a galloylated derivative of paeoniflorin isolated from peony root, has been proven to possess antioxidant potential. In this present study, we revealed that GPF treatment exerted significant neuroprotection of PC12 cells following OGD, as evidenced by a reduction of oxidative stress, inflammatory response, cellular injury, and apoptosis in vitro. Furthermore, treatment with GPF increased the levels of phosphorylated Akt (p-Akt) and nuclear factor-erythroid 2-related factor 2 (Nrf2), as well as promoted Nrf2 translocation in PC12 cells, which could be inhibited by Ly294002, an inhibitor of phosphoinositide 3-kinase (PI3K). In addition, Nrf2 knockdown or Ly294002 treatment significantly attenuated the antioxidant, anti-inflammatory, and antiapoptotic activities of GPF in vitro. In vivo studies indicated that GPF treatment significantly reduced infarct volume and improved neurological deficits in rats subjected to CIRI, as well as decreased oxidative stress, inflammation, and apoptosis, which could be inhibited by administration of Ly294002. In conclusion, these results revealed that GPF possesses neuroprotective effects against oxidative stress, inflammation, and apoptosis after ischemia-reperfusion insult via activation of the PI3K/Akt/Nrf2 pathway.

• Authors: Zhongmei Wen, Weichen Hou, Wei Wu, Yang Zhao, Xuechao Dong, Xiaoxue Bai, Liping Peng, Lei Song
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2018 Pg. 8678267 ( 2018) ISSN: 1942-0994 [Electronic] United States
• PMID: 29765506 (Publication Type: Journal Article)

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Glucosides
• Monoterpenes
• Neuroprotective Agents
• galloylpaeoniflorin
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Brain Ischemia (drug therapy, pathology)
• Bridged Bicyclo Compounds, Heterocyclic (pharmacology, therapeutic use)
• Cell Line, Tumor
• Glucosides (pharmacology, therapeutic use)
• Male
• Monoterpenes (pharmacology, therapeutic use)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Oxidative Stress (drug effects)
• PC12 Cells (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt
• Rats
• Rats, Wistar
• Reperfusion Injury (drug therapy)