title: Emodin-induced microglial apoptosis is associated with TRB3 induction.
abstract: Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a natural anthraquinone compound isolated from the rhizome of rhubarb, has been reported to treat brain injury after intracerebral hemorrhage. Treatment of neurons with emodin is able to decrease glutamate excitotoxicity, modulate calcium homeostasis, and induce Bcl-2 expression. However, the effects of emodin on the brain-resident innate immune cells are unclear. In the present study, the mouse microglial cell line, BV-2, was selected to investigate the effects of emodin on microglial activation and apoptosis. Cell viability and apoptosis were sequentially measured with the CellTiter-Glo Luminescent Cell Viability Assay, YOPRO-1 and Caspase-Glo 3/7 Assay Systems. The degree of microglial activation was evaluated using quantitative RT-PCR to measure expression of inflammatory markers. Treatment of BV-2 cells with emodin caused caspase-mediated apoptosis in a dose-dependent manner, and emodin augmented LPS-induced microglial apoptosis to repress inflammatory activation. In response to emodin treatment, reactive oxygen species (ROS) production was increased, and TRB3 was markedly activated. siRNA knockdown of TRB3 attenuated emodin-induced microglial apoptosis. Ectopic overexpression of TRB3 decreased cell viability and was associated with dysregulation of the prosurvival Akt/FOXO3 pathway. These results demonstrate that emodin induces BV-2 cell apoptosis through TRB3 and consequently eliminates inflammatory microglia. Our findings provide a novel molecular basis through which emodin exerts neuroprotective effects, treating brain injury after intracerebral hemorrhage.
authors.affiliation: The Clinical Research Institute, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Zhou
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Mingyan
authors.initials: M
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Taihui
authors.initials: T
authors.lastname: Fang
authors.forename: Mianhua
authors.initials: M
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D001930:Brain Injuries / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004642:Emodin / Q000494:pharmacology*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; C474830:TRB3 protein, mouse; D020169:Caspases; D004642:Emodin