title: Ginsenoside Rg1 protects against sepsis-associated encephalopathy through beclin 1-independent autophagy in mice.
abstract: Sepsis-associated encephalopathy (SAE), a commonly complicated syndrome, is associated with increased mortality in patients with sepsis. Currently, no specific diagnostic test or effective intervention exists to improve long-term consequences on cerebral function. Ginsenoside Rg1 (Rg1), a major component in ginseng, was reported to have pleiotropic properties including anti-inflammation and neuroprotection. The aim of our study was to investigate the protective effect of Rg1 on SAE and the potential mechanism.
  
  
  
  SAE model was prepared by inducing cecal ligation and puncture (CLP) in mice. Rg1 was injected 1 h before the CLP operation. Survival rate within 7 d after operation was analyzed. Surviving mice were subjected to Morris water maze tests and the brains were collected for histopathologic evaluation and immunohistochemistry. The hippocampus was obtained for Western blot, real time polymerase chain reaction, and enzyme-linked immunosorbent assay analysis.
  
  
  
  Rg1 improved the postoperative survival rate and protected against sepsis-associated learning and memory impairments (Morris water maze). Besides, Rg1 was able to attenuate brain histopathologic changes (hematoxylin and eosin staining), suppress Iba1 activation, decrease the expressions of inflammatory cytokines (tumor necrosis factor α, interleukin 1β, and interleukin 6), and reduce neuronal apoptosis (cleaved caspase 3 activation) in hippocampus. Furthermore, the mechanism study showed that Rg1 suppressed the expressions of light chain 3-II and p62 in hippocampus but not beclin 1.
  
  
  
  These findings suggested that Rg1 improved the survival rate and ameliorated cognitive impairments partially through regulating cerebral inflammation and apoptosis. In addition, the action mechanism might be noncanonical beclin 1-independent autophagy pathway. Rg1 may be a promising treatment strategy for SAE.
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Yinjiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. Electronic address: ly11087@rjh.com.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D000071186:Beclin-1 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D036145:Ginsenosides / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D018805:Sepsis / Q000150:complications*; D065166:Sepsis-Associated Encephalopathy / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000071186:Beclin-1; D015415:Biomarkers; D036145:Ginsenosides; D018696:Neuroprotective Agents; C035054:ginsenoside Rg1
keywords: Autophagy; Cognitive impairment; Ginsenoside Rg1; Inflammation; Sepsis-associated encephalopathy