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Korean red ginseng ameliorated experimental pancreatitis through the inhibition of hydrogen sulfide in mice
Affiliation:1. Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India;4. Bhabha Atomic Research Centre, Mumbai, Maharashtra, India;1. Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan;2. Department of Pathology, Shizuoka Cancer Center, Shizuoka 411-8777, Japan;1. Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA;2. Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA;3. Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, USA;4. Institute of Food, Nutrition and Health, Swiss Federal Institute of Technology Zurich, Schwerzenbach 8603, Switzerland
Abstract:AimEffective therapy to treat acute pancreatitis (AP) or to prevent its recurrence/complication is still not available. Based on previous results that suggest that: i) hydrogen sulfide (H2S) levels were significantly increased in pancreatitis and gastritis and ii) Korean red ginseng (KRG) efficiently attenuated Helicobacter pylori-associated gastritis through the suppressive actions of H2S, we hypothesized that KRG can ameliorate experimental pancreatitis through suppression of H2S generation.MethodsC57BL/6 mice were pre-administered KRG and then subjected to cerulein injection or pancreatic duct ligation (PDL) to induce pancreatitis. Blood and pancreas tissues were collected and processed to measure serum levels of amylase, lipase and myeloperoxidase and the concentration of H2S and the levels of various inflammatory cytokine in pancreatic tissues of mice with induced AP.ResultsKRG significantly inhibited NaHS-induced COX-2 and TNF-α mRNA in pancreatic cells, but dl-propargylglycine did not. KRG ameliorated cerulein-induced edematous pancreatitis accompanied with significant inactivation of NF-κB and JNK in pancreatic tissues of C57BL/6 mice (p < 0.001) and also significantly ameliorated PDL-induced necrotizing pancreatitis (p<0.01); in both conditions, the significant suppression of H2S resulting from KRG pretreatment afforded rescuing outcomes. Along with suppressed levels of H2S consequent to depressed expressions of CBS and CSE mRNA, KRG administration efficiently decreased the serum level of amylase, lipase, and myeloperoxidase and the expression of inflammatory cytokines in animal models of mild or severe AP.ConclusionsThese results provide evidence for the preventive and therapeutic roles of KRG against AP mediated by H2S suppression.
Keywords:Hydrogen sulfide  Cystathionine γ-lyase (CSE)  Cystathione-β-synthase (CBS)  Cerulein-induced pancreatitis  Pancreatic duct ligation-induced necrotizing pancreatitis  Korean red ginseng
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