PMID- 23973786 OWN - NLM STAT- MEDLINE DCOM- 20140519 LR - 20131011 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 150 IP - 1 DP - 2013 Oct 28 TI - Neuroprotective effects of Polygonum multiflorum extract against glutamate-induced oxidative toxicity in HT22 hippocampal cells. PG - 108-15 LID - S0378-8741(13)00556-4 [pii] LID - 10.1016/j.jep.2013.08.014 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND 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. CI - (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Kim, Ha Neui AU - Kim HN AD - Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea. FAU - Kim, Yu Ri AU - Kim YR FAU - Jang, Ji Yeon AU - Jang JY FAU - Choi, Young Whan AU - Choi YW FAU - Baek, Jin Ung AU - Baek JU FAU - Hong, Jin Woo AU - Hong JW FAU - Choi, Yung Hyun AU - Choi YH FAU - Shin, Hwa Kyoung AU - Shin HK FAU - Choi, Byung Tae AU - Choi BT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130822 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Creb1 protein, mouse) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Neuroprotective Agents) RN - 0 (Plant Extracts) RN - 3KX376GY7L (Glutamic Acid) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.4.22.- (Calpain) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Calpain/metabolism MH - Cell Line MH - Cell Survival/drug effects MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Glutamic Acid MH - Hippocampus/cytology MH - Mice MH - Mitogen-Activated Protein Kinases/metabolism MH - Neuroprotective Agents/*pharmacology MH - Oxidative Stress/drug effects MH - Plant Extracts/*pharmacology MH - Plant Roots MH - *Polygonum OTO - NOTNLM OT - ERK OT - HT22 cell OT - Oxidative neurotoxicity OT - Polygonum multiflorum OT - p38 EDAT- 2013/08/27 06:00 MHDA- 2014/05/20 06:00 CRDT- 2013/08/27 06:00 PHST- 2013/04/12 00:00 [received] PHST- 2013/07/12 00:00 [revised] PHST- 2013/08/11 00:00 [accepted] PHST- 2013/08/27 06:00 [entrez] PHST- 2013/08/27 06:00 [pubmed] PHST- 2014/05/20 06:00 [medline] AID - S0378-8741(13)00556-4 [pii] AID - 10.1016/j.jep.2013.08.014 [doi] PST - ppublish SO - J Ethnopharmacol. 2013 Oct 28;150(1):108-15. doi: 10.1016/j.jep.2013.08.014. Epub 2013 Aug 22.