title: Attenuation of cysteamine-induced duodenal ulcer with Cochinchina momordica seed extract through inhibiting cytoplasmic phospholipase A2/5-lipoxygenase and activating γ-glutamylcysteine synthetase.
abstract: OBJECTIVE
  Cysteamine is a reducing aminothiol used for inducing duodenal ulcer through mechanisms of oxidative stress related to thiol-derived H(2)O(2) reaction. Cochinchina momordica saponins have been suggested to be protective against various gastric diseases based on their cytoprotective and anti-inflammatory mechanisms. This study was aimed to document the preventive effects of Cochinchina momordica seed extract against cysteamine-induced duodenal ulcer as well as the elucidation of its pharmacological mechanisms.
  
  
  METHODS
  Cochinchina momordica seed extract (50, 100, 200 mg/kg) was administrated intragastrically before cysteamine administration, after which the incidence of the duodenal ulcer, ulcer size, serum gastrin level, and the ratio of reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG) as well as biochemical and molecular measurements of cytoplasmic phospholipase A(2) (cPLA(2)), cyclooxygenase-2 (COX-2), 5-lipoxygenase and the expression of proinflammatory genes including IL-1β, IL-6, COX-2 were measured in rat model. Additional experiments of electron spin resonance measurement and the changes of glutathione were performed.
  
  
  RESULTS
  Cochinchina momordica seed extract effectively prevented cysteamine-induced duodenal ulcer in a dose-dependent manner as reflected with significant decreases in either duodenal ulcerogenesis or perforation accompanied with significantly decreased in serum gastrin in addition to inflammatory mediators including cPLA(2), COX-2, and 5-lipoxygenase. Cochinchina momordica seed extract induced the expression of γ-glutamylcysteine synthetase (γ-GCS)-related glutathione synthesis as well as significantly reduced the expression of cPLA(2). Cochinchina momordica seed extract preserved reduced glutathione through increased expressions of γ-GCS.
  
  
  CONCLUSIONS
  Cochinchina momordica seed extracts exerted significantly protective effect against cysteamine-induced duodenal ulcer by either cPLA2 inhibition or glutathione preservation.
authors.affiliation: Laboratory of Translational Medicine, Gachon University Lee Gil Ya Cancer and Diabetes Institute, Incheon, Korea.
authors.forename: Ki-Seok
authors.initials: KS
authors.lastname: Choi
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.forename: Hua
authors.initials: H
authors.lastname: Hong
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Ock
authors.forename: Jeong Sang
authors.initials: JS
authors.lastname: Lee
authors.forename: Joo-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Ki-Baik
authors.initials: KB
authors.lastname: Hahm
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003543:Cysteamine; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D004386:Duodenum / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000302:isolation & purification / Q000494:pharmacology*; D005755:Gastrins / Q000097:blood; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016859:Lipoxygenase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D029775:Momordica / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D054510:Phospholipases A2, Cytosolic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds; D013997:Time Factors
chemical_list: D000897:Anti-Ulcer Agents; D000975:Antioxidants; D020536:Enzyme Activators; D005755:Gastrins; D018836:Inflammation Mediators; D016859:Lipoxygenase Inhibitors; D010936:Plant Extracts; D003543:Cysteamine; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D054510:Phospholipases A2, Cytosolic; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione