title: Effect of emodin on endoplasmic reticulum stress in rats with severe acute pancreatitis.
abstract: This study aimed to investigate the protective effect of emodin on endoplasmic reticulum (ER) stress in rats with severe acute pancreatitis (SAP) and the underlying molecular mechanism. Sprague-Dawley male rats were randomly divided into sham operation group, SAP model group, and emodin treatment group. SAP was constructed through injecting sodium taurocholate into pancreatic and biliary duct in rats. Half an hour before establishing the animal model, emodin or sodium carboxymethylcellulose was intragastrically administrated to the rats in respective group. Rats were killed at 3, 6, and 12 h postdisease induction. The amylase, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels in serum, pancreatic histopathology, acinar ER ultrastructure, protein expression of Bip, IRE1α,TRAF2, ASK1, p-JNK, and p-p38 MAPK in pancreas were examined. Sodium taurocholate induced pancreatic injury and ER lumen dilated in exocrine pancreas in rats at 3-, 6-, and 12-h time points. ER stress transducers Bip, IRE1α, and their downstream molecules TRAF2, ASK1 in pancreatitis were upregulated. Furthermore, phosphorylation of JNK and p38MAPK in pancreas was increased, which induced high expression level of inflammatory cytokines such as TNF-α and IL-6. Treatment with emodin obviously ameliorated pancreatic injury and decreased the release of amylase and inflammatory cytokines. Further studies showed that emodin significantly decreased the expression of Bip, IRE1α, TRAF2, and ASK1, inhibited phosphorylation of JNK and p38 MAPK in pancreas in rats at all time points. Emodin could reduce pancreatic injury and restrain inflammatory reaction in SAP rats partly via inhibiting ER stress transducers IRE1α and its downstream molecules.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Baochang
authors.initials: B
authors.lastname: Cai
authors.forename: Shizhong
authors.initials: S
authors.lastname: Zheng
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Cai
authors.forename: Huan
authors.initials: H
authors.lastname: Li
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D002266:Carboxymethylcellulose Sodium; D004642:Emodin / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004722:Endoribonucleases / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D015850:Interleukin-6 / Q000097:blood; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D010179:Pancreas / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000188:drug therapy*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000681:Amylases; D002266:Carboxymethylcellulose Sodium; D004642:Emodin; D004722:Endoribonucleases; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D048031:JNK Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; D009097:Multienzyme Complexes; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D047992:TNF Receptor-Associated Factor 2; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C575026:Ern1 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP