Cytoprotective effects of lindenenyl acetate isolated from Lindera strychnifolia on mouse hippocampal HT22 cells.
Oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as Parkinson's disease, Alzheimer's disease, epilepsy and ischemia. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a role in the pathogenesis of these diseases. Lindenenyl acetate, isolated by bioassay-guided fractionation of the MeOH extract of the roots of Lindera strychnifolia, showed potent neuroprotective effects on glutamate-induced neurotoxicity by inducing the expression of HO-1 and increasing the activity of HO in mouse hippocampal HT22 cells. Furthermore, lindenenyl acetate caused the nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and increased the promoter activity of antioxidant response elements (ARE) in mouse hippocampal HT22 cells. In addition, we found that treatment of the cells with extracellular signal-regulated kinase (ERK) inhibitor (U0126) reduced lindenenyl acetate-induced HO-1 expression. Lindenenyl acetate also increased ERK phosphorylation. These results suggest that lindenenyl acetate increases cellular resistance to glutamate-induced oxidative injury in mouse hippocampal HT22 cells, presumably through the ERK pathway-Nrf2/ARE-dependent HO-1 expression.
Li
Bin
B
College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
Jeong
Gil-Saeng
GS
Kang
Dae-Gill
DG
Lee
Ho-Sub
HS
Kim
Youn-Chul
YC
D000085:Acetates / Q000302:isolation & purification* / Q000494:pharmacology*; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D005453:Fluorescence; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D027443:Lindera / Q000737:chemistry*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D018517:Plant Roots / Q000737:chemistry; D012717:Sesquiterpenes / Q000302:isolation & purification* / Q000494:pharmacology*
D000085:Acetates; D000975:Antioxidants; D005452:Fluoresceins; D051267:NF-E2-Related Factor 2; D012717:Sesquiterpenes; C543034:lindenenyl acetate; C029569:diacetyldichlorofluorescein; D018698:Glutamic Acid; D051547:Heme Oxygenase-1; D048049:Extracellular Signal-Regulated MAP Kinases