Neuroprotective effects of constituents of the root bark of Dictamnus dasycarpus in mouse hippocampal cells.
Glutamate-induced oxidative injury causes neuronal degeneration related to many central nervous system diseases, such as Parkinson's disease, Alzheimer's disease, epilepsy and ischemia. The bioassay-guided fractionation of the EtOH extract of the root bark of Dictamnus dasycarpus Trucz. provided one neuroprotective limonoid, obacunone, together with a degraded limonoid, fraxinellone and two alkaloids, dictamine and haplopine. At concentrations of 100-150 microM, obacunone showed the potent neuroprotective effects on glutamateinduced neurotoxicity and induced the expression of heme oxygenase (HO)-1 in the mouse hippocampal HT22 cells. In addition, we found that obacunone increased p38 MAPK phosphorylation and induced HO-1 expression via p38 MAPK pathway. These results suggest that obacunone isolated from the root bark of D. dasycarpus increases cellular resistance to glutamate-induced oxidative injury in mouse hippocampal HT22 cells, presumably through the p38 MAPK pathway-dependent HO-1 expression. These results suggest that obacunone could be the effective candidates for the treatment of ROS-related neurological diseases.
Jeong
Gil-Saeng
GS
Zoonosis Research Center, Wonkwang University, Iksan, 570-749, Korea.
Byun
Erisa
E
Li
Bin
B
Lee
Dong-Sung
DS
Kim
Youn-Chul
YC
An
Ren-Bo
RB
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D036905:Dictamnus / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018696:Neuroprotective Agents; D010936:Plant Extracts; D018698:Glutamic Acid; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases