title: Magnesium isoglycyrrhizinate inhibits inflammatory response through STAT3 pathway to protect remnant liver function.
abstract: OBJECTIVE
  To investigate the protective effect of magnesium isoglycyrrhizinate (MgIG) on excessive hepatectomy animal model and its possible mechanism.
  
  
  METHODS
  We used the standard 90% hepatectomy model in Sprague-Dawley rats developed using the modified Emond's method, in which the left, middle, right upper, and right lower lobes of the liver were removed. Rats with 90% liver resection were divided into three groups, and were injected intraperitoneally with 3 mL saline (control group), 30 mg/kg (low-dose group) and 60 mg/kg (high-dose group) of MgIG, respectively. Animals were sacrificed at various time points and blood was drawn from the vena cava. Biochemical tests were performed with an automatic biochemical analyzer for the following items: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl endopeptidase, total bilirubin (TBil), direct bilirubin (DBil), total protein, albumin, blood glucose (Glu), hyper-sensitivity C-reactive protein, prothrombin time (PT), and thrombin time (TT). Postoperative survival time was observed hourly until death. Hepatocyte regeneration was analyzed by immunohistochemistry. Serum inflammatory cytokines (IL-1, IL-6, IL-10, and iNOS) was analyzed by ELISA. STAT3 protein and mRNA were analyzed by Western blot and quantitative reverse-transcription PCR, respectively.
  
  
  RESULTS
  The high-dose group demonstrated a significantly prolonged survival time, compared with both the control and the low-dose groups (22.0 ± 4.7 h vs 8.9 ± 2.0 vs 10.3 ± 3.3 h, P = 0.018). There were significant differences among the groups in ALT, Glu and PT levels starting from 6 h after surgery. The ALT levels were significantly lower in the MgIG treated groups than in the control group. Both Glu and PT levels were significantly higher in the MgIG treated groups than in the control group. At 12 h, ALT, AST, TBil, DBil and TT levels showed significant differences between the MgIG treated groups and the control group. No significant differences in hepatocyte regeneration were found. Compared to the control group, the high-dose group showed a significantly increase in serum inflammatory cytokines IL-1 and IL-10, and a decrease in IL-6. Both STAT3 protein and mRNA levels were significantly lower in the MgIG treated groups than in the control group at 6 h, 12 h, and 18 h after surgery.
  
  
  CONCLUSIONS
  High-dose MgIG can extend survival time in rats after excessive hepatectomy. This hepatoprotective effect is mediated by inhibiting the inflammatory response through inhibition of the STAT3 pathway.
authors.affiliation: Guang-Hua Tang, Hua-Yu Yang, Jin-Chun Zhang, Jin-Jun Ren, Xin-Ting Sang, Xin Lu, Shou-Xian Zhong, Yi-Lei Mao, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing 100730, China.
authors.forename: Guang-Hua
authors.initials: GH
authors.lastname: Tang
authors.affiliation: Guang-Hua Tang, Hua-Yu Yang, Jin-Chun Zhang, Jin-Jun Ren, Xin-Ting Sang, Xin Lu, Shou-Xian Zhong, Yi-Lei Mao, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing 100730, China.
authors.forename: Hua-Yu
authors.initials: HY
authors.lastname: Yang
authors.affiliation: Guang-Hua Tang, Hua-Yu Yang, Jin-Chun Zhang, Jin-Jun Ren, Xin-Ting Sang, Xin Lu, Shou-Xian Zhong, Yi-Lei Mao, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing 100730, China.
authors.forename: Jin-Chun
authors.initials: JC
authors.lastname: Zhang
authors.affiliation: Guang-Hua Tang, Hua-Yu Yang, Jin-Chun Zhang, Jin-Jun Ren, Xin-Ting Sang, Xin Lu, Shou-Xian Zhong, Yi-Lei Mao, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing 100730, China.
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Ren
authors.affiliation: Guang-Hua Tang, Hua-Yu Yang, Jin-Chun Zhang, Jin-Jun Ren, Xin-Ting Sang, Xin Lu, Shou-Xian Zhong, Yi-Lei Mao, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing 100730, China.
authors.forename: Xin-Ting
authors.initials: XT
authors.lastname: Sang
authors.affiliation: Guang-Hua Tang, Hua-Yu Yang, Jin-Chun Zhang, Jin-Jun Ren, Xin-Ting Sang, Xin Lu, Shou-Xian Zhong, Yi-Lei Mao, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing 100730, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Guang-Hua Tang, Hua-Yu Yang, Jin-Chun Zhang, Jin-Jun Ren, Xin-Ting Sang, Xin Lu, Shou-Xian Zhong, Yi-Lei Mao, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing 100730, China.
authors.forename: Shou-Xian
authors.initials: SX
authors.lastname: Zhong
authors.affiliation: Guang-Hua Tang, Hua-Yu Yang, Jin-Chun Zhang, Jin-Jun Ren, Xin-Ting Sang, Xin Lu, Shou-Xian Zhong, Yi-Lei Mao, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing 100730, China.
authors.forename: Yi-Lei
authors.initials: YL
authors.lastname: Mao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D006498:Hepatectomy / Q000009:adverse effects*; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: C521270:18alpha,20beta-hydroxy-11-oxo-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranurosyl-alpha-D-glucopyranosiduronate magnesium tetrahydrate; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D050796:STAT3 Transcription Factor; D012503:Saponins; C494088:Stat3 protein, rat; D014315:Triterpenes
keywords: Excessive liver resection; Inflammation; Liver regeneration; Magnesium isoglycyrrhizinate; STAT3