Heme Oxygenase-1-Inducing Activity of 4-Methoxydalbergione and 4’-Hydroxy-4-methoxydalbergione from Dalbergia odorifera and Their Anti-inflammatory and Cytoprotective Effects in Murine Hippocampal and BV2 Microglial Cell Line and Primary Rat Microglial Cells
Autor: | Hyuncheol Oh, Hye Jin Kim, Dong-Cheol Kim, Dong-Sung Lee, Chi-Su Yoon, Youn-Chul Kim, Kwan-Woo Kim, Wonmin Ko |
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Rok vydání: | 2017 |
Předmět: |
Lipopolysaccharides
0301 basic medicine MAPK/ERK pathway Dalbergia p38 mitogen-activated protein kinases medicine.medical_treatment Anti-Inflammatory Agents Nitric Oxide Synthase Type II Pharmacology Toxicology Hippocampus Cell Line Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine hemic and lymphatic diseases Benzoquinones medicine Animals neoplasms Neuroinflammation Microglia General Neuroscience Neurotoxicity medicine.disease Rats respiratory tract diseases Heme oxygenase Neuroprotective Agents 030104 developmental biology medicine.anatomical_structure Cytokine chemistry Biochemistry therapeutics Heme Oxygenase-1 030217 neurology & neurosurgery |
Zdroj: | Neurotoxicity Research. 33:337-352 |
ISSN: | 1476-3524 1029-8428 |
Popis: | Dalbergia odorifera T. Chen (Leguminosae) grows in Central and South America, Africa, Madagascar, and Southern Asia. D. odorifera possesses many useful pharmacological properties, such as antioxidative and anti-inflammatory activities in various cell types. 4-Methoxydalbergione (MTD) and 4'-hydroxy-4-methoxydalbergione (HMTD) were isolated from the EtOH extract of D. odorifera by several chromatography methods. The chemical structures were elucidated by nuclear magnetic resonance (NMR) and mass spectrum (MS). Anti-inflammatory and cytoprotective effects were examined using BV2 microglial cells and murine hippocampus. MTD and HMTD were demonstrated to induce heme oxygenase (HO)-1 protein levels through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in BV2 microglial cells, while only MTD upregulated HO-1 in HT22 cells. MTD and HMTD induced HO-1 expression through JNK MAPK pathway in BV2 cells, whereas only MTD activated the ERK and p38 pathways in HT22 cells. MTD was also shown to activated MTD and HMTD suppressed lipopolysaccharide-stimulated nitric oxide (NO) and prostaglandin E2 production by inhibiting inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in a dose-dependent manner. Furthermore, MTD and HMTD attenuated pro-inflammatory cytokine productions. These anti-inflammatory effects were found to be mediated through the nuclear factor-kappa B (NF-κB) pathway. MTD exhibited neuroprotective effects on glutamate-induced neurotoxicity by promoting HO-1 in HT22 cells. The anti-inflammatory and cytoprotective effects of MTD and HMTD were partially reversed by an HO inhibitor tin protoporphyrin IX. In addition, MTD and HMTD inhibited pro-inflammatory cytokines and NF-κB pathway in primary rat microglia. These findings suggest that MTD and HMTD have therapeutic potential against neurodegenerative diseases accompanied by microglial activation and/or oxidative cellular injury. |
Databáze: | OpenAIRE |
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