Neuroprotective Effect of the Water-insoluble fraction of Root Barks of Dictamnus dasycarpus 70% Ethanolic Extract on Glutamate-Induced Oxidative Damage in Mouse Hippocampal HT22 Cells

백선피 70% 에탄올 추출물의 비수용성 분획물의 뇌세포 보호 효과

  • Choi, Hyun-Gyu (Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University) ;
  • Lee, Dong-Sung (Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University) ;
  • Li, Bin (Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University) ;
  • Jun, Ki-Yong (Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University) ;
  • Jeong, Gil-Saeng (College of Pharmacy, Keimyung University) ;
  • Kim, Youn-Chul (Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University)
  • Received : 2011.04.14
  • Accepted : 2011.05.23
  • Published : 2011.06.30

Abstract

Oxidative stress or accumulation of reactive oxygen species (ROS) leads neuronal cellular death and dysfunction, and it contributes to neuronal degenerative disease such as Alzheimer's disease, Parkinson's disease and stroke. Glutamate is one of the major excitatory neurotransmitter in the central nervous system (CNS). Glutamate contributes to fast synaptic transmission, neuronal plasticity, outgrowth and survival, behavior, learning and memory. In spite of these physiological functions, high concentration of glutamate causes neuronal cell damage, acute insults and chronic neuronal neurodegenerative diseases. Heme oxygenase-1 (HO-1) enzyme plays an important role of cellular antioxidant system against oxidant injury. NNMBS020, the water-insoluble fraction of the 70% EtOH extract of root barks of Dictamnus dasycarpus, showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells by induced the expression of HO-1 and increased HO activity. In mouse hippocampal HT22 cells, NNMBS020 makes the nuclear accumulation of Nrf2 and stimulates extracellular signal-regulated kinase (ERK) pathway. The ERK MAPK pathway inhibitor significantly reduced NNMBS020-induced HO-1 expression, whereas the JNK and p38 inhibitors did not. In conclusion, the water-insoluble fraction of the 70% EtOH extract of root barks of D. dasycarpus (NNMBS020) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 and ERK pathway in mouse hippocampal HT22 cells.

Keywords

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