Neuroprotective effects of constituents of the root bark of Dictamnus dasycarpus in mouse hippocampal cells

• Published in: Archives of pharmacal research Vol. 33; no. 8; pp. 1269 - 1275
• Main Authors: Jeong, Gil-Saeng, Byun, Erisa, Li, Bin, Lee, Dong-Sung, An, Ren-Bo, Kim, Youn-Chul
• Format: Journal Article
• Language: English
• Published: Heidelberg Pharmaceutical Society of Korea 01.08.2010; 대한약학회
• Subjects: Animals; Cell Line; Cell Survival - drug effects; Dictamnus - chemistry; Dose-Response Relationship, Drug; Gene Expression Regulation - drug effects; Glutamic Acid - toxicity; Heme Oxygenase-1 - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; Medicine; Mice; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - isolation & purification; Neuroprotective Agents - pharmacology; p38 Mitogen-Activated Protein Kinases - metabolism; Pharmacology/Toxicology; Pharmacy; Phosphorylation - drug effects; Plant Extracts - administration & dosage; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Roots; 약학; Glutamate-induced toxicity; Obacunone; HT22; p38 MAPK; Heme oxygenase-1
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-010-0818-9

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 μM, 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.