title: Neuroprotective effects of Polygonum multiflorum extract against glutamate-induced oxidative toxicity in HT22 hippocampal cells.
abstract: BACKGROUND
  Dried roots of Polygonum multiflorum have traditionally been used in the retarding of aging process in East Asian countries and its extracts exhibit anti-oxidative activities.
  
  
  METHODS
  Neuroprotective effects of ethyl acetate extract from Polygonum multiflorum (EEPM) were investigated against glutamate-induced oxidative cell death in HT22 hippocampal cells. Cell viability, cytotoxicity, morphological, flow cytometry, and Western blot assays were performed in order to observe alterations of neuronal cell survival or death related pathways.
  
  
  RESULTS
  Pretreatment with EEPM resulted in significantly decreased glutamate-induced neurotoxicity and also resulted in drastically inhibited glutamate-induced apoptotic and necrotic neuronal death. To elucidate possible pathways of neuroprotection by EEPM, we explored the activation of mitogen activated protein kinases (MAPKs), phosphatidylinositol-3-kinase, and cAMP responsive element binding protein (CREB). Treatment with glutamate alone led to activation of extracellular regulated kinase (ERK), Jun N-terminal kinase, and p38 during the late phase after glutamate exposure, but pretreatment with EEPM resulted in significantly attenuated activation of these proteins. Pretreatment with EEPM resulted in increased activation of CREB. The specific inhibitors of ERK and p38, PD98059 and SB203580, abrogated the neuroprotective effects of EEPM. When we evaluated calpain I and striatal-enriched protein tyrosine phosphatase (STEP), active form of calpain I was significantly increased after glutamate exposure, and, along with this, active form of STEP showed a decrease. Pretreatment with EEPM resulted in significant recovery of pro-calpain I and active form of STEP caused by glutamate. Co-treatment with calpain inhibitor ALLN and EEPM had a synergistic effect on neuronal death and contributed to blockade of activation of both ERK and p38 with increased activation of CREB.
  
  
  CONCLUSIONS
  These results suggest that Polygonum multiflorum extract may have neuroprotective effects through both alleviation of ERK and p38 activation with increased activation of CREB under oxidative stress and has potential as a therapeutic intervention for treatment of oxidative neuronal death.
authors: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
authors: Ha Neui
authors: HN
authors: Kim
authors: Yu Ri
authors: YR
authors: Kim
authors: Ji Yeon
authors: JY
authors: Jang
authors: Young Whan
authors: YW
authors: Choi
authors: Jin Ung
authors: JU
authors: Baek
authors: Jin Woo
authors: JW
authors: Hong
authors: Yung Hyun
authors: YH
authors: Choi
authors: Hwa Kyoung
authors: HK
authors: Shin
authors: Byung Tae
authors: BT
authors: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002154:Calpain / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D018698:Glutamic Acid; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D028502:Polygonum
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D010936:Plant Extracts; D018698:Glutamic Acid; D020928:Mitogen-Activated Protein Kinases; D002154:Calpain
keywords: ERK; HT22 cell; Oxidative neurotoxicity; Polygonum multiflorum; p38