title: Total aralosides of aralia elata (Miq) seem (TASAES) ameliorate nonalcoholic steatohepatitis by modulating IRE1α-mediated JNK and NF-κB pathways in ApoE-/- mice.
abstract: BACKGROUND
  Total saponins of Aralia elata (Miq) Seem (TASAES) from the Chinese traditional herb Long ya Aralia chinensis L. is popularly used as a folk medicine to treat rheumatism, neurasthenia, diabetes, hepatitis and antivirus in Asian countries. However, there was poor study of TASAES on Non-alcoholic steatohepatitis (NASH), which is characterized by inflammatory responses and hepatocellular apoptosis exacerbating liver injury. This study aimed to clarify whether or not the anti-inflammatory and anti-apoptotic activities and protective mechanisms of the total aralosides of Aralia elata (Miq) Seem (TASAES) ameliorate NASH in a high-fat diet (HFD)-induced ApoE-/- mouse model.
  
  
  METHODS
  C57/BL6N and ApoE-/- mice were fed with HFD containing 0.3% cholesterol and 20% fat to induce NASH and then treated with TASAES (75,150mg/kg/day, i.g.) for 12 weeks. Liver tissue was procured for histological examination, real-time RT-PCR and Western blot analysis.
  
  
  RESULTS
  ASAES treatment groups exhibited lower serum alanine and aspartate aminotransferases than the NASH group. TASAES could also reduce hepatic steatosis, as revealed by histological changes. In addition, TASAES treatment groups showed lower protein and mRNA expression levels of pro-inflammatory cytokines, such as IL-6, MCP-1, and TNF-α than NASH group. Reduced TUNEL-positive cells were also found in TASAES treatment groups. Western blot and immunohistochemical results indicated that TASAES regulated apoptosis and inflammation-related protein expression. Furthermore, TASAES treatment significantly reduced the phosphorylation of IRE1α, JNK and IκB and the downstream activation of NF-κB p65 was also reduced.
  
  
  CONCLUSIONS
  These findings suggested that the ameliorative effects of TASASE in HFD-induced NASH were associated with the regulation of IRE1α-mediated JNK and NF-κB signal pathways, thereby protecting the liver against NASH.
authors: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China.
authors: Yun
authors: Y
authors: Luo
authors: Academy of Chinese Materia Medica, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Xi
authors: X
authors: Dong
authors: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China.
authors: Yingli
authors: Y
authors: Yu
authors: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China. Electronic address: sunguibo@126.com.
authors: Guibo
authors: G
authors: Sun
authors: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China. Electronic address: sunsubmit@163.com.
authors: Xiaobo
authors: X
authors: Sun
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D027983:Aralia; D059305:Diet, High-Fat; D004722:Endoribonucleases / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; D016328:NF-kappa B; D012503:Saponins; D009828:Oleanolic Acid; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D048670:MAP Kinase Kinase 4; D004722:Endoribonucleases
keywords: Hepatocyte apoptosis; Inflammatory cytokines; JNK; NASH; NF-κB; TASAES