title: Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity.
abstract: BACKGROUND
  Mitrella kentii (M. kentii) (Bl.) Miq, is a tree-climbing liana that belongs to the family Annonaceae. The plant is rich with isoquinoline alkaloids, terpenylated dihydrochalcones and benzoic acids and has been reported to possess anti-inflammatory activity. The purpose of this study is to assess the gastroprotective effects of desmosdumotin C (DES), a new isolated bioactive compound from M. kentii, on gastric ulcer models in rats.
  
  
  METHODS
  DES was isolated from the bark of M. kentii. Experimental rats were orally pretreated with 5, 10 and 20 mg/kg of the isolated compound and were subsequently subjected to absolute ethanol-induced acute gastric ulcer. Gross evaluation, mucus content, gastric acidity and histological gastric lesions were assessed in vivo. The effects of DES on the anti-oxidant system, non-protein sulfhydryl (NP-SH) content, nitric oxide (NO)level, cyclooxygenase-2 (COX-2) enzyme activity, bcl-2-associated X (Bax) protein expression and Helicabacter pylori (H pylori) were also investigated.
  
  
  RESULTS
  DES pre-treatment at the administered doses significantly attenuated ethanol-induced gastric ulcer; this was observed by decreased gastric ulcer area, reduced or absence of edema and leucocytes infiltration compared to the ulcer control group. It was found that DES maintained glutathione (GSH) level, decreased malondialdehyde (MDA) level, increased NP-SH content and NO level and inhibited COX-2 activity. The compound up regulated heat shock protein-70 (HSP-70) and down regulated Bax protein expression in the ulcerated tissue. DES showed interesting anti-H pylori effects. The efficacy of DES was accomplished safely without any signs of toxicity.
  
  
  CONCLUSIONS
  The current study reveals that DES demonstrated gastroprotective effects which could be attributed to its antioxidant effect, activation of HSP-70 protein, intervention with COX-2 inflammatory pathway and potent anti H pylori effect.
authors.forename: Heyam Mohamed Ali
authors.initials: HM
authors.lastname: Sidahmed
authors.forename: Ainnul Hamidah Syahadah
authors.initials: AH
authors.lastname: Azizan
authors.forename: Syam
authors.initials: S
authors.lastname: Mohan
authors.forename: Mahmood Ameen
authors.initials: MA
authors.lastname: Abdulla
authors.forename: Siddig Ibrahim
authors.initials: SI
authors.lastname: Abdelwahab
authors.forename: Manal Mohamed Elhassan
authors.initials: MM
authors.lastname: Taha
authors.forename: A Hamid A
authors.initials: AH
authors.lastname: Hadi
authors.forename: Kamal Aziz
authors.initials: KA
authors.lastname: Ketuly
authors.forename: Najihah Mohd
authors.initials: NM
authors.lastname: Hashim
authors.forename: Mun Fai
authors.initials: MF
authors.lastname: Loke
authors.forename: Jamuna
authors.initials: J
authors.lastname: Vadivelu
mesh_terms: D000475:Alkenes / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D029061:Annonaceae / Q000737:chemistry*; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D016481:Helicobacter Infections / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000187:drug effects; D006470:Hemorrhage / Q000517:prevention & control; D007659:Ketones / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000475:Alkenes; D000897:Anti-Ulcer Agents; D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; D007659:Ketones; D010936:Plant Extracts; D013438:Sulfhydryl Compounds; D051028:bcl-2-Associated X Protein; C502470:desmosdumotin C; D009569:Nitric Oxide; D000431:Ethanol; D008315:Malondialdehyde; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D005978:Glutathione