title: Neuroprotective effects of neolignans isolated from Magnoliae Cortex against glutamate-induced apoptotic stimuli in HT22 cells.
abstract: In the course of screening for neuroprotective natural products, Magnoliae Cortex showed potent inhibition of hippocampal neuronal HT22 cell death. Obovatol, honokiol, and magnolol were isolated from the ethanolic extract of Magnoliae Cortex. Isolated compounds obovatol, honokiol, and magnolol were protective against 5mM glutamate-induced cell death. When cells were stressed using glutamate, cell viability decreased to 16.98±4.58% over the control (100.00±10.15%). In contrast, 10 μM obovatol, 10 μM honokiol, and 50 μM magnolol increased cell viability to 91.80±1.70%, 93.59±1.93%, and 85.36±7.40%, respectively. The neuroprotective effects of obovatol and honokiol were attributable to the inhibition of intracellular reactive oxygen species production, followed by protection of the mitochondrial membrane potential (ΔΨm), recovery of Bcl-2 and Bid levels, inhibition of apoptosis-inducing factor expression, and phosphorylation of mitogen-activated protein kinases such as p38 kinases, extracellular signal-regulated kinases, and c-Jun N-terminal kinases. On the contrary, magnolol did not show any significant effect on the ΔΨm and apoptotic factors. Among three compounds, obovatol most strongly scavenged 2,2-diphenyl-1-picrylhydrazyl radicals and inhibited the elevation of intracellular reactive oxygen species levels in glutamate-stressed HT22 cells. These data suggest that obovatol and honokiol may have clinical applications for preventing neurodegenerative disorders.
authors: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daehak-ro 80, Daegu 702-701, Republic of Korea.
authors: Eun-Ju
authors: EJ
authors: Yang
authors: Joon-Yeop
authors: JY
authors: Lee
authors: Se-Hoon
authors: SH
authors: Park
authors: Taeho
authors: T
authors: Lee
authors: Kyung-Sik
authors: KS
authors: Song
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018698:Glutamic Acid / Q000009:adverse effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D029562:Magnoliaceae / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010647:Phenyl Ethers / Q000494:pharmacology; D010766:Phosphorylation; D010851:Picrates / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D051033:Apoptosis Inducing Factor; D051023:BH3 Interacting Domain Death Agonist Protein; D001713:Biphenyl Compounds; D048049:Extracellular Signal-Regulated MAP Kinases; D018698:Glutamic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D017705:Lignans; D018696:Neuroprotective Agents; D010647:Phenyl Ethers; D010851:Picrates; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases; C494815:Bid protein, mouse; C005498:magnolol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C036795:obovatol; C004931:1,1-diphenyl-2-picrylhydrazyl