Neuroprotective effects of Polygonum multiflorum extract against glutamate-induced oxidative toxicity in HT22 hippocampal cells

• Published in: Journal of ethnopharmacology 2013-10, Vol.150 (1), p.108-115
• Main Authors: Kim, Ha Neui, Kim, Yu Ri, Jang, Ji Yeon, Choi, Young Whan, Baek, Jin Ung, Hong, Jin Woo, Choi, Yung Hyun, Shin, Hwa Kyoung, Choi, Byung Tae
• Format: Article
• Language: English
• Subjects: acetates; Animals; antioxidant activity; apoptosis; Apoptosis - drug effects; binding proteins; calpain; Calpain - metabolism; Cell Line; Cell Survival - drug effects; cell viability; cyclic AMP; Cyclic AMP Response Element-Binding Protein - metabolism; cytotoxicity; death; ERK; flow cytometry; Glutamic Acid; Hippocampus - cytology; HT22 cell; Mice; mitogen-activated protein kinase; Mitogen-Activated Protein Kinases - metabolism; Neuroprotective Agents - pharmacology; neurotoxicity; Oxidative neurotoxicity; oxidative stress; Oxidative Stress - drug effects; p38; phosphatidylinositol 3-kinase; Plant Extracts - pharmacology; Plant Roots; Polygonum; Polygonum multiflorum; protein-tyrosine-phosphatase; roots; synergism; Western blotting
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2013.08.014

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. 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. 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. 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. [Display omitted]