title: Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogenesis via improving 5-HT metabolism.
abstract: Sepsis, in addition to causing fatality, is an independent risk factor for cognitive impairment among sepsis survivors. The pathologic mechanism of endotoxemia induced acute neuro-inflammation still has not been fully understood. For the first time, we found the disruption of neurotransmitters 5-HT, impaired neurogenesis and activation of astrocytes coupled with concomitant neuro-inflammation were the potential pathogenesis of endotoxemia induced acute neuro-inflammation in sepsis survivors. In addition, dioscin a natural steroidal saponin isolated from Chinese medicinal herbs, enhanced the serotonergic system and produced anti-depressant effect by enhancing 5-HT levels in hippocampus. What is more, this finding was verified by metabolic analyses of hippocampus, indicating 5-HT related metabolic pathway was involved in the pathogenesis of endotoxemia induced acute neuro-inflammation. Moreover, neuro-inflammation and neurogenesis within hippocampus were indexed using quantitative immunofluorescence analysis of GFAP DCX and Ki67, as well as real-time RT-PCR analysis of some gene expression levels in hippocampus. Our in vivo and in vitro studies show dioscin protects hippocampus from endotoxemia induced cascade neuro-inflammation through neurotransmitter 5-HT and HMGB-1/TLR4 signaling pathway, which accounts for the dioscin therapeutic effect in behavioral tests. Therefore, the current findings suggest that dioscin could be a potential approach for the therapy of endotoxemia induced acute neuro-inflammation.
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Yingke
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Du
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Songyan
authors.initials: S
authors.lastname: Gao
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Yuan
mesh_terms: D000818:Animals; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004660:Encephalitis / Q000188:drug therapy*; D019446:Endotoxemia / Q000150:complications*; D020869:Gene Expression Profiling; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006624:Hippocampus / Q000473:pathology / Q000502:physiology; D019394:Ki-67 Antigen / Q000032:analysis; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000032:analysis; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000378:metabolism*
chemical_list: C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D017366:Serotonin Receptor Agonists; C528900:glial fibrillary astrocytic protein, mouse; D012701:Serotonin; C019357:dioscin; D004144:Diosgenin