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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Gastroprotective effects of goniothalamin against ethanol and indomethacin-induced gastric lesions in rats: Role of prostaglandins, nitric oxide and sulfhydryl compounds

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Vendramini-Costa, Debora Barbosa [1, 2] ; Monteiro, Karin Maia [2] ; Iwamoto, Leilane Hespporte [2, 3] ; Jorge, Michelle Pedroza [2] ; Tinti, Sirlene Valerio [2] ; Pilli, Ronaldo Aloise [1] ; de Carvalho, Joao Ernesto [2, 3, 4]
Total Authors: 7
[1] Univ Estadual Campinas, Inst Chem, Dept Organ Chem, BR-13081970 Campinas, SP - Brazil
[2] Univ Estadual Campinas, CPQBA, Chem Biol & Agr Pluridisciplinary Res Ctr, BR-13148218 Paulinia, SP - Brazil
[3] Univ Estadual Campinas, Fac Dent, Dept Pharmacol Anaesthesiol & Therapeut, BR-13414903 Piracicaba, SP - Brazil
[4] Univ Estadual Campinas, Fac Pharmaceut Sci, BR-13081970 Campinas, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Chemico-Biological Interactions; v. 224, p. 206-212, DEC 5 2014.
Web of Science Citations: 12

Goniothalamin (GTN), a styryl-lactone, is a secondary metabolite naturally found in its enantiomeric form (R) in plants of the genus Goniothalamus (Annonaceae). The antiproliferative activity against human tumor cell lines reported in several studies suggest that the alpha,beta-unsaturated delta-lactone moiety emerges as a key Michael acceptor for cysteine residues or other nucleophilic biological molecules. Our group reported on the in vivo activity of (R)- and (S)-GTN as well as its racemic form (rac-GTN) in both Ehrlich solid tumor and carrageenan-induced paw edema in mice, without side effects in the effective doses. Despite the rich body of data on the in vitro GTN biological activity, much less is known about its in vivo pharmacological action. Herein we describe the gastroprotective activity of rac-GTN on chemical-induced gastric ulcers models in rats. GTN has a potent gastroprotective effect on ethanol-induced ulcers (effective dose(50) = 18 mg/kg) and this activity is dependent on sulfhydryl compounds and prostaglandins generation, but independent of nitric oxide (NO), gastric secretion and mucus production. We hypothesize that goniothalamin may act as a mild irritant, inducing the production of sulfhydryl compounds and prostaglandins, in a process known as adaptive cytoprotection. This hypothesis is supported by the fact that Michael acceptors are the most potent inducers of antioxidant response (as activation of Nrf2 pathway) through generation of mild oxidative stress and that gastroprotective activity of goniothalamin is inhibited after pre-treatment with NEM (N-ethylmaleimide) and NSAID (non-steroidal anti-inflammatory drugs), highlighting the importance of sulfhydryl compounds and prostaglandins on GIN activity. (C) 2014 Elsevier Ireland Ltd. All rights reserved. (AU)

FAPESP's process: 12/18281-3 - Mechanism of action of goniothalamin and derivatives: the use of fluorescent probes and folate receptors
Grantee:Débora Barbosa Vendramini Costa
Support Opportunities: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 09/51602-5 - Chemical biology: new natural and synthetic molecular targets against cancer, structural studies, biological evaluation and mode of action
Grantee:Ronaldo Aloise Pilli
Support Opportunities: Research Projects - Thematic Grants